Patent Publication Number: US-2023140653-A1

Title: Noninvasive molecular clock for fetal development predicts gestational age and preterm delivery

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a national phase application of PCT Application No. PCT/US2018/057142, filed Oct. 23, 2018, which claims benefit of U.S. Provisional Application No. 62/576,033 (filed Oct. 23, 2017) and No. 62/578,360 (filed Oct. 27, 2017), each of which is hereby incorporated by reference in its entirety. 
    
    
     FIELD OF THE INVENTION 
     The invention is in the field of medicine. 
     SEQUENCE LISTING 
     The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Oct. 17, 2018, is named 103182-1107145_(000300PC)_SL.txt and is 159,304 bytes in size. 
     BACKGROUND 
     Understanding the timing and program of human development has been a topic of interest for thousands of years. In antiquity, the ancient Greeks had surprisingly detailed knowledge of various details of stages of fetal development, and they developed mathematical theories to try to account for the timing of important landmarks during development including delivery of the baby (Hanson 1995; Hanson 1987; Parker 1999). In the modern era, biologists have put together a detailed cellular and molecular portrait of both fetal and placental development. However, these results relate to pregnancy in general and have not led to molecular tests, which might enable monitoring of development and prediction of delivery for a given set of parents. The most widely used molecular metrics of development are determining the levels of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP), which can be used to detect conception and fetal complications, respectively; however, neither molecule either individually or in conjunction has been found to precisely establish gestational age (Dugoff et al. 2005; Yefet et al. 2017). 
     Due to the lack of a useful molecular test, most clinicians use either ultrasound imaging or the patient&#39;s estimate of last menstruation period (LMP) in order to establish gestational age and a rough estimate for delivery date. However, these methods are neither particularly precise nor useful for predicting preterm delivery, which is a substantial source of mortality and cost in prenatal healthcare. Moreover, inaccurate dating can misguide the assessment of fetal development even for normal term pregnancies, which has been shown to ultimately lead to unnecessary induction of labor and cesarean sections, extended post-natal care, and increased expendable medical expenses (Bennett et al. 2004; Whitworth et al. 2015). 
     It would be useful both to develop a more precise approach to measure the gestational age of the fetus at various points in pregnancy, and more generally to monitor fetal and placental development for signs of abnormality or preterm delivery. Approximately 15 million neonates are born preterm every year worldwide (Blencowe et al. 2013). As the leading cause of neonatal death and the second cause of childhood death under the age of 5 years (Liu et al. 2012), premature delivery is estimated to annually cost the United States upward of $26.2 billion (Institute of Medicine (US) Committee on Understanding Premature Birth and Assuring Healthy Outcomes 2007). The complications continue later into life as preterm birth is a leading cause of life years lost to ill health, disability, or early death (Murray et al. 2012). Two-thirds of preterm delivery occur spontaneously, and the only predictors are a history of preterm birth, multiple gestations, and vaginal bleeding (Institute of Medicine (US) Committee on Understanding Premature Birth and Assuring Healthy Outcomes 2007). Efforts to find a genetic cause have had only limited success (Ward et al. 2005; York et al. 2009) and therefore most effort is focused on phenotypic and environmental causes (Muglia and Katz 2010). 
     BRIEF SUMMARY 
     Gestational age or time to delivery may be determined by (a) generating an expression profile using cfRNA or protein from a maternal sample, and (b) comparing the expression profile with one or more reference profiles that reflect an expression profile characteristic of a defined gestational age. 
     Risk of preterm delivery may be determined by (a) generating an expression profile using cfRNA (or protein) from a maternal sample, and (b) determining whether the expression profile is or is not characteristic of a population with a history of preterm delivery and/or whether the expression profile is or is not characteristic of a population with a history of full-term delivery. 
     In a first aspect, the disclosure provides a method of estimating gestational age of a fetus comprising, analyzing a maternal sample to determine an expression profile from a panel comprising one or more placental genes. 
     In some embodiments, the method includes an expression profile comprising three or more placental genes. In some embodiments, the method includes an expression profile from a panel comprising only of placental genes. 
     In some embodiments, the method further includes the expression level of each of the placental genes changing during the course of pregnancy. In some embodiments, the method includes the expression level of at least one placental gene is that is higher in the first trimester compared to the third trimester. In some versions, the expression level of all of the placental genes are lower in the first trimester compared to the third trimester. In some embodiments, the method includes the expression level of at least one placental gene that is lower in the first trimester compared to the third trimester. 
     In some embodiments, the method includes the placental genes selected from genes in TABLE 1. In some embodiments, the method includes the placental genes selected from CGA, CAPN6, CGB, ALPP, CSHL1, PLAC4, PSG7, PAPPA, and LGALS14. 
     In some embodiments, the method includes determining the expression profiles for three to nine placental genes. In some embodiments, the method includes determining the expression profile by measuring cell-free RNAs (cfRNAs) in the maternal sample. In some embodiments, the method includes determining the expression profile by measuring placental proteins in the maternal sample. 
     In some embodiments, the method includes a maternal sample from blood, blood plasma, blood serum, or urine. In some embodiments, the method includes a maternal sample obtained from the mother during the third trimester of pregnancy. In some embodiments, the method includes a maternal sample obtained from the mother during the second trimester of pregnancy. 
     In some embodiments, the method includes the steps: comparing the expression profile with a plurality of reference profiles, wherein each reference profile is characteristic of a defined gestational age, determining which of the plurality of reference profiles corresponds to the expression profile based on the comparing, and deducing the estimated gestational age of the fetus at the time the maternal sample was obtained based on the defined gestational age of the corresponding reference profile. 
     In a second aspect, the disclosure provides a method for estimating gestational age of a fetus including the steps: (a) obtaining a maternal expression profile for a sample, comprising expression levels for a panel of genes according to any of the embodiments of the first aspect, and (b) comparing expression levels to reference expression levels for the panel of genes, wherein the reference expression levels are obtained from a full-term delivery population, to determine whether the maternal expression profile is similar to, or is different from, the reference expression levels within a threshold. 
     In some embodiments, the method includes one or more reference expression levels for the full-term population are established using a machine learning technique. In some versions, the method further includes obtaining a plurality of training samples, each labeled as preterm or full-term, obtaining one or more measured expression levels for the panel of genes for each of the plurality of training samples, and iteratively adjusting the one or more reference expression levels using the machine learning technique to increase a number of the training samples that are classified correctly as a result of comparing the one or more measured expression levels to the one or more reference expression levels. 
     In some embodiments, the method further includes the steps: comparing the expression levels to other reference expression levels for the panel of genes, wherein the other reference expression levels are obtained from a preterm delivery population, to determine whether the maternal expression profile is similar to, or is different from, the other reference expression levels within a threshold. 
     In a third aspect, the disclosure provides a method for estimating gestational age of a fetus including the steps of: (i) determining a maternal expression profile of a panel comprising at least one placental RNA, and (ii) comparing the maternal expression profile to a reference profile, wherein the comparison of the maternal expression profile to the reference profile allows for the for estimation of gestational age. In some embodiments, the gestational age is known for the reference profile. In some embodiments, the comparison of the maternal expression profile to the reference profile is performed by comparing the maternal expression profile to a gestational function that provides a gestational age based on an input of one or more expression levels, wherein the gestational function is determined by fitting a model to a plurality of calibration samples having measured expression levels and of which a gestational age is known. In some versions, the method uses a regression model. 
     In some embodiments, the method includes a profile panel described in any of the embodiments of the first aspect. In some embodiments, the method is carried out by a computer. 
     In some embodiments, the method includes determining a first gestational age according to the method of the first or second aspect using a first maternal sample and determining a second gestational age according to the method of the first or second aspect using a second maternal sample obtained later in pregnancy. 
     The method of the first aspect, wherein the expression levels of individual placental genes are determined by qPCR or massively parallel sequencing. 
     The method of the first aspect, wherein the expression levels of individual placental genes are determined by mass spectrometry or using an antibody array. 
     The method of the first, second, or third aspect, wherein the expression of at least one additional gene is determined, and the additional gene is not a placental gene. 
     In a fourth aspect, the disclosure provides a composition comprising, primers for multiplex amplification of at least three and no more than fifty placental genes selected TABLE 1. 
     In a fifth aspect, the disclosure provides a kit comprising, primers suitable for multiplex amplification of at least three, and no more than fifty, placental genes selected from TABLE 1. 
     In a sixth aspect, the disclosure provides an antibody array for detecting at least three and no more than one hundred placental proteins isolated from maternal blood or urine. 
     In a seventh aspect, the disclosure provides a method for assessing risk of preterm delivery by a pregnant woman comprising, analyzing a maternal sample to determine an expression profile from a panel comprising one or more genes selected from TABLE 2. 
     In some embodiments, the method includes a panel comprising three or more genes from TABLE 2. In some embodiments, the method includes genes having higher expression levels in a preterm population than in a term population. In some embodiments, the method includes genes selected from: CLCN3, DAPP1, POLE2, PPBP, LYPLAL1, MAP3K7CL, MOB1B, RAB27B, RGS18, and TBC1D15, or from: CLCN3, DAPP1, PPBP, MAP3K7CL, MOB1B, RAB27B, and RGS18. In some embodiments, the method includes a panel comprising three genes selected from any combination of three from: CLCN3, DAPP1, POLE2, PPBP, LYPLAL1, MAP3K7CL, MOB1B, RAB27B, RGS18, and TBC1D15 (ten transcript panel), or from: CLCN3, DAPP1, PPBP, MAP3K7CL, MOB1B, RAB27B, and RGS18 (seven transcript panel). 
     In some embodiments, the method includes the expression profiles in which a panel of three to ten genes are determined. In some embodiments, the method includes the expression profile in which a panel comprising exactly three genes are determined. 
     In some versions the method includes, determining the expression profile by measuring cell-free RNAs (cfRNAs) in the maternal sample. In some embodiments, the method includes determining the expression profile by measuring proteins in the maternal sample. 
     In some embodiments, the method includes a maternal sample from blood, blood plasma, blood serum, or urine. In some embodiments, the method includes a maternal sample obtained more than 28 days prior to preterm delivery. In some embodiments, the method includes a maternal sample obtained more than 45 days prior to preterm delivery. In some embodiments, the method includes a maternal sample obtained after the second month and prior to the eighth month of pregnancy. In some embodiments, the method includes a maternal sample obtained during the second trimester of pregnancy. 
     In some versions, a maternal sample is obtained during the third trimester of pregnancy. 
     In some embodiments, the method of the seventh aspect includes, a maternal sample obtained at a specified week of pregnancy, comprising the steps: comparing the expression profile to a time matched reference profile, wherein the time matched reference profile is characteristic of a normal term pregnancy at the specified week of pregnancy, and identifying the pregnant woman as an elevated risk for preterm delivery if the expression profile differs significantly from the time matched reference profile within a threshold. 
     In some embodiments, the method of the seventh aspect includes a maternal sample obtained at a specified week of pregnancy, comprising the steps: comparing the expression profile to a time matched reference profile, wherein the time matched reference profile is characteristic of a preterm pregnancy, and identifying the pregnant woman as an elevated risk for preterm delivery if the expression profile is significantly similar to the time matched reference profile within a threshold. 
     In an eighth aspect, the disclosure provides a method for assessing risk of preterm delivery of a pregnant woman comprising the steps: (a) obtaining a maternal expression profile for a sample, comprising expression levels for a panel of genes according to the seventh aspect of the disclosure, and (b) comparing the expression levels to reference expression levels for the panel of genes, wherein the reference expression levels are obtained from a preterm delivery population, a full-term delivery population, or both populations, to determine whether the maternal expression profile is similar to, or is different from, the reference expression levels within a threshold. 
     In some embodiments, the method one or more reference levels are established using a machine learning technique. 
     In some embodiments, the methods of the seventh or eighth aspect are carried out by a computer. 
     In a ninth aspect, the disclosure provides a method including carrying out the steps of the claims provided in the seventh or eighth aspect with two or more maternal samples obtained at different times during the course of a pregnancy. 
     The method of the seventh aspect, wherein the expression levels of individual genes are determined by qPCR or massively parallel sequencing. 
     The method of the seventh aspect, wherein the expression levels of individual genes are determined by mass spectrometry or an antibody array. 
     In a tenth aspect, the disclosure provides a composition comprising primers for multiplex amplification of at least three genes selected from TABLE 2 and no more than one hundred different genes. 
     In an eleventh aspect, the disclosure provides a kit comprising primers for multiplex amplification of at least three genes selected from TABLE 2 and no more than one hundred different genes. 
     In a twelfth aspect, the disclosure provides a method of estimating time to delivery comprising analyzing a maternal sample to determine an expression profile from a panel comprising one or more placental genes. 
     In some embodiments, the method includes an expression profile from a panel comprising three or more placental genes. 
     In some embodiments, the method includes an expression profile from a panel comprised only of placental genes. 
     In some embodiments, the method includes the expression level of each of the placental genes changes during the course of pregnancy. In some embodiments, the method includes the expression level of at least one placental gene that is higher in the first trimester compared to the third trimester. In some embodiments, the method includes the expression level of at least one placental gene that is lower in the first trimester compared to the third trimester. In some versions, the expression levels of all of the placental genes are lower in the first trimester compared to the third trimester. 
     In some embodiments, the method includes determining the expression profile by measuring cell-free RNAs (cfRNAs) in the maternal sample. In some embodiments, the method includes determining the expression profile by measuring placental proteins in the maternal sample. 
     In some embodiments, the method includes a maternal sample from blood, blood plasma, blood serum, or urine. 
     In some embodiments, the method includes a maternal sample obtained from the mother during the third trimester of pregnancy. 
     In some embodiments, the method includes a maternal sample obtained from the mother during the second trimester of pregnancy. 
     In some embodiments, the method includes the steps: comparing the expression profile with a plurality of reference profiles, wherein each reference profile is characteristic of a time to delivery, determining which of the plurality of reference profiles corresponds to the expression profile, and deducing the estimated time to delivery at the time the maternal sample was obtained based on the time to delivery of the corresponding reference profile. 
     In a thirteenth aspect, the disclosure provides a method for estimating time to delivery including the steps: (a) obtaining a maternal expression profile for a sample, comprising expression levels for a panel of genes according to any one of the embodiments of the ninth and seventh aspect, and (b) comparing the expression levels to reference expression levels for the panel of genes, wherein the reference expression levels are obtained from a full-term delivery population to determine whether the maternal expression profile is similar to, or is different from, the reference expressions levels within a threshold. 
     In some embodiments, the method includes one or more reference levels for the full-term population are established using a machine learning technique. In some embodiments, the method is carried out by a computer. 
     In some embodiments, the method includes determining a first time to delivery according to the method of the twelfth or thirteenth aspect using a first maternal sample and determining a second time to delivery according to the method of the twelfth or thirteenth aspect using a second maternal sample obtained later in pregnancy. 
     The method of the twelfth aspect, wherein the expression levels of individual placental genes are determined by qPCR or massively parallel sequencing. 
     The method of the twelfth aspect, wherein the expression levels of individual placental genes are determined by mass spectrometry or an antibody array. 
     The method of the twelfth or thirteenth aspect, wherein expression of at least one additional gene is determined, and the additional gene is not a placental gene. 
     In a fourteenth aspect, the disclosure provides a composition comprising, primers for multiplex amplification of at least three placental genes selected from TABLE 1 and no more than one hundred different genes. 
     In a fifteenth aspect, the disclosure provides a kit comprising, primers for the multiplex amplification of at least three genes selected from TABLE 1 and no more than one hundred placental genes. 
     In a sixteenth aspect, the disclosure provides an antibody array for detecting at least three and no more than one hundred placental proteins isolated from maternal blood or urine. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS.  1 A- 1 B  are temporal graphs showing collection timelines from pregnant women in three different cohorts: Denmark ( FIG.  1 A ), Pennsylvania and Alabama ( FIG.  1 B ). Squares, inverted triangles, and lines indicate sample collection, delivery date, and individual patients, respectively. 
         FIG.  2 A  shows data from representative gene expression arrays of placenta, immune or organ specific genes (last row). Gene-specific inter-patient monthly averages±standard error of the mean (SEM) plotted over the course of gestation (shaded in gray). † represents genes for which data for only 21 patients was available. 
         FIG.  2 B  is a heatmap showing correlation between gene-specific estimated transcript counts. Genes are listed in the same order as  FIG.  2 A  while omitting genes for which data was only available for 21 patients. Placental (rows/columns 1-20), immune (rows/columns 21-29) and organ specific genes (rows/columns 30-36) are shown. 
         FIGS.  2 C- 2 D  show solid lines and shading that indicate linear fit and 95% confidence intervals, respectively.  FIG.  2 C  shows an exemplary random forest model prediction of time to delivery for training data (n=21, R=0.91, P&lt;2.2×10 −16 , cross-validation).  FIG.  2 D  shows an exemplary random forest model prediction of time to delivery for validation data (n=10, R=0.89, P&lt;2.2×10 −16 ). 
         FIG.  2 E  are graphs showing comparison of expected delivery date prediction during the second, third trimester, or both second and third trimesters, by ultrasound or cell-free RNA methods of the invention. 
         FIG.  3 A  shows a heat map for 40 differentially expressed genes (p&lt;0.001) between preterm deliveries and normal deliveries. RNA-Seq was performed on samples from Pennsylvania. 
         FIG.  3 B  shows individual plots of 10 genes identified and validated in an independent cohort from Alabama, which accurately predicted preterm delivery using any unique combination of 3 genes from this set. All p-values reported are calculated using the Fisher exact test (FDR&lt;5%). *, **, and *** indicate significance levels below 0.05, 0.005, and 0.0005, respectively. 
         FIG.  3 C  is a graph showing predictive performance of the 10 validated preterm biomarkers in unique combinations of 3 genes from  FIG.  3 B . Area under the curve (AUC) values are highlighted both for the discovery (Pennsylvania and Denmark) and validation (Alabama) cohorts. 
         FIG.  4    shows data from representative gene expression arrays of placenta or immune genes. Gene-specific inter-patient monthly averages±standard error of the mean (SEM) plotted over the course of gestation (shaded in gray). t represents genes for which data for only 21 patients was available. 
         FIG.  5    shows a random forest model built using 9 placental genes outperforming a random forest model built using 51 genes of placental, immune and tissue-specific organ origin to predict gestational age by root mean squared error (RMSE). 
         FIGS.  6 A and  6 B  show solid lines and shading indicating a linear fit and 95% confidence intervals, respectively.  FIG.  6 A  shows an exemplary random forest model prediction of gestational age for training data (n=21, R=0.91, P&lt;2.2×10 −16 , cross-validation) and  FIG.  6 B  shows an exemplary random forest model prediction of gestational age for validation data (n=10, R=0.90, P&lt;2.2×10 −16 ) 
         FIGS.  7 A and  7 B  show solid lines and shading indicating a linear fit and 95% confidence intervals, respectively. Training and validation data are reported above each graph. Random forest model prediction of gestational age and time to delivery for normal and preterm samples reveals that although the model works well for prediction of gestational age for normal deliveries (RMSE=4.5) and preterm deliveries (RMSE=4.7) ( FIG.  7 A ), it fails to accurately predict time to delivery in the preterm cases (RMSE=10.5 weeks) ( FIG.  7 B ); while accurately predicting time to delivery for normal deliveries ( FIG.  7 B ). 
         FIG.  8    shows RT-qPCR measurements agree with previously determined RNA-Seq values. 
         FIG.  9    shows C t  counts for each gene under evaluation are back-calculated from C t  values using a standard curve generated using a common set of external RNA controls developed by the External RNA Controls Consortium (ERCC). The control consists of a set of unlabeled, polyadenylated transcripts designed to be added to an RNA analysis experiment after sample isolation and prior to interrogation. ERCC Spike-In Control Mixes are commercially available, pre-formulated blends of 92 transcripts, designed to be 250 to 2,000 nucleotides in length, which mimic natural eukaryotic mRNAs (e.g., ERCC RNA Spike-In Mix, Invitrogen, CA, Catalog No. 4456740). 
         FIGS.  10 A- 10 D  provide an exemplary list of genes found to be significantly different between spontaneous preterm delivery and normal delivery samples using three statistical analyses. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     1. INTRODUCTION 
     We have discovered a panel of genetic biomarkers for non-invasively predicting gestational age or time to delivery of a fetus in a pregnant woman. We have also discovered an orthogonal set of genetic biomarkers for non-invasively predicting whether a woman is at risk for preterm delivery of a fetus. The discovery that a set of genetic markers for predicting gestational age or time to delivery of a fetus is significant, in part, because of the potential advantages of replacing ultrasounds as the gold standard for predicting gestational age and thus avoiding substantial health care expenses associated with ultrasounds and sonographers. Additionally, the discovery that a set of genetic markers for predicting whether a woman is at risk for preterm delivery is also significant, in part, because of the potential advantages of prophylactically treating women at risk from preterm delivery and thus negating substantial health care expenses associated with neonatal intensive care units (NICU&#39;s). 
     We performed a high time-resolution study of normal human development by measuring cfRNA in blood from pregnant women longitudinally during each week of pregnancy. Analysis of tissue-specific transcripts in these samples enabled us to follow fetal and placental development with high resolution and sensitivity, and also to detect gene-specific response of the maternal immune system to pregnancy. The data from this study establish a “clock” for normal human development and enable a direct molecular approach to establish expected delivery date with comparable accuracy to ultrasound at a fraction of the cost. We also identified an orthogonal gene set that accurately discriminates women at risk of preterm delivery up to two months in advance of labor, forming the basis of a screening or diagnostic test for risk of prematurity. 
     2. DEFINITIONS 
     As used herein, the terms “cell free RNA” or “cfRNA” refer to RNA, especially mRNA, expressed by cells of the mother, fetus and/or placenta and recoverable from the non-cellular fraction of maternal blood, and includes fragments of full-length RNA transcripts. In some embodiments “cfRNA” does not include rRNA. In some embodiments “cfRNA” does not include miRNA. In some embodiments “cfRNA” refers to mRNA. Cf RNA can also be recovered from maternal urine. 
     As used herein, the terms “placental gene,” “placental gene product,” “placental cfRNA,” or “placental protein” refer to a gene or corresponding gene product that is expressed in the placenta but not expressed (or expressed at significantly lower levels) by maternal or fetal tissues. Publicly available resources exist to identify placental genes including databases such as Tissue-Specific Gene Expression and Regulation (TiGER) which identifies 377 RefSeq (NCBI Reference Sequence Database) genes as being preferentially expressed in the placenta (http://bioinfo.wilmer.jhu.edu/tiger). Other databases such as Expression Atlas (https://www.ebi.ac.uk/gxa/home) can also be used to identify placental genes. Placental gene products include mRNA and protein. 
     As used herein, the term “expression profile,” refers to the level of expression of one or a plurality of gene products obtained from a maternal sample. The gene products may be cfRNAs or proteins. For gene products recovered from maternal plasma, expression levels may be expressed as the number of transcripts of a specified RNA per mL maternal plasma, mass of a specified polypeptide per mL maternal plasma, transcript count calculated from RNA-Seq, or any other suitable units. Analogous units may be used for gene products obtained from other maternal samples, such as urine. Expression of gene products may be determined using any suitable method (e.g., as described below). Measured values are typically normalized to account for variations in the quantity and quality of the sample, reverse-transcription efficiency, and the like. When an expression profile reflects expression from multiple different gene products (e.g., different cfRNA transcripts) the gene products may be given different weights when generating or comparing expression profiles or reference profiles. For example, when comparing an expression profile comprising cfRNA 1 and cfRNA 2 in a sample from a pregnant woman with a reference profile (discussed below), a 2-fold difference in values for cfRNA 1 may be given more weight than a 2-fold difference in values for cfRNA 2 in determining a degree of similarity or difference between the expression profile and the reference profile. An expression profile from a maternal (e.g., patient) sample is sometimes referred to as a “maternal expression profile” and a maternal expression profile from a sample collected at a specified time may be referred to as a “[time] maternal expression profile,” e.g., a “24 week maternal expression profile.” 
     As used herein, a “reference profile” is an expression profile derived from a reference population. For illustration, examples of reference populations are pregnant women, pregnant women who delivered at term, or pregnant women who delivered prematurely. In some embodiments the reference population is a subpopulation of pregnant women characterized by maternal age (e.g., women 20-25 years old who delivered at term), race or ethnicity (e.g., African-American women who delivered at term), and the like. A reference profile is generated by combining expression profiles of a statistically significant number of women in the population and, for a specified gene product, may reflect the mean transcript level in the population, the median transcript level in the population, or may be determined using any of a number of methods known in the fields of epidemiology and medicine. A reference population will typically comprise at least 10 subjects (e.g., 10-200 subjects), sometimes 50 or more subjects, and sometimes 1000 or more subjects. 
     As used herein, the term “profile panel” refers to the set of gene products measured in a particular assay. For example, in an assay for six (6) different cfRNAs (“RNAs A-F”), those six cfRNAs would be the profile panel. Likewise, in an assay for six (6) different proteins from maternal plasma or urine, those six proteins would be the profile panel. As another illustration, in an assay in which expression data are collected for transcripts of a large number of genes (e.g., the entire transcriptome, or a large number of placental gene transcripts) the subset used for estimating gestational age or time to delivery, or assessing risk of preterm delivery may be referred to as the profile panel. It will be recognized that measurements of RNAs or proteins not included in the panel may be used as controls, to normalize measurements within or across samples, or for similar uses. In some embodiments a profile panel may include a set of gene products that includes both cfRNAs and proteins. A profile panel is sometimes referred to as a “panel.” 
     As used herein, the terms “preterm pregnancy,” “preterm delivery,” “full-term pregnancy,” “full-term delivery,” and “normal term pregnancy” have their normal meanings. Full-term refers to delivery after the fetus reached a gestational age of 37 weeks and preterm refers to delivery prior to the fetus reaching a gestational age of 37 weeks. In some contexts preterm refers to delivery in the period from 16 weeks to 35 weeks gestational age or 24 weeks to 30 weeks gestational age. Preterm populations used in the studies discussed below (see Examples) delivered a fetus prior to 29 weeks gestational age in one case (Pennsylvania cohort) and 33 weeks gestational age in another (Alabama cohort). See  FIG.  1   . 
     As used herein, “maternal sample” refers sample of a body fluid obtained from a pregnant woman. The body fluid is typically serum, plasma, or urine, and is usually serum. In some embodiments a sample of a different body fluid may be used, such as saliva, cerebrospinal fluid, pleural effusions, and the like. Maternal samples may be obtained at multiple different time points during pregnancy and stored (e.g., frozen) until assayed. It will be appreciated that the date of collection of a maternal sample is an integral property of the sample. 
     As used herein, “time to delivery” refers to the number of weeks from a specified time (present time, date of maternal sample collection) to the delivery date or predicted delivery date. Time to delivery is calculated as (gestational age at delivery) minus (gestational age at sample collection). 
     As used herein, the terms “protein” and “polypeptide” are used interchangeably. Reference to a protein obtained from a maternal sample does not necessarily imply that the protein is a full-length gene expression product. Portions, fragments, and cleavage products may be detected and identifed according to the invention. 
     3. ILLUSTRATIVE METHODS AND EMBODIMENTS USING CELL-FREE RNA EXPRESSION PROFILES 
     The invention relates to discovery of a high resolution molecular clock for fetal development and the invention of methods to establish time to delivery, fetal gestational age, and risk of preterm delivery. In one aspect, methods and materials for estimating gestational age or time to delivery of a fetus using expression profiles of placental gene(s) are described. In another aspect, methods and materials for assessing risk of preterm delivery are described. 
     For illustration and not limitation, gestational age or time to delivery may be determined by (a) generating an expression profile using cfRNA (or protein) from a maternal sample and (b) comparing the expression profile with one or more reference profiles that reflect an expression profile characteristic of a defined gestational age. For illustration, the maternal expression profile is compared to 37 reference profiles (characteristic of 1 through 37 weeks of gestational age) and gestational age or time to delivery is estimated based on the relatedness of the maternal expression profile to one of the 37 reference profiles. For illustration and not limitation, risk of preterm delivery may be determined by (a) generating an expression profile using cfRNA (or protein) from a maternal sample and (b) determining whether the expression profile is or is not characteristic of a population with a history of preterm delivery and/or whether the expression profile is or is not characteristic of a population with a history of full-term delivery. In another approach, machine learning (e.g., random forest regression, support vector machines, elastic net, lasso) is used to predict gestational age, time to delivery, and risk of prematurity based on the maternal expression profile generated from a maternal sample. 
     3.1 Obtaining the Maternal Sample 
     A maternal sample (e.g., plasma or urine) may be collected and cfRNA may be isolated from the sample immediately or after storage. See Example 1 below. Art-known methods may be employed to guard the RNA fraction against degradation including, for example, use of special collection tubes (e.g. PAXgene RNA tubes from Preanalytix, Tempus Blood RNA tubes from Applied Biosystems) or additives (e.g. RNAlater from Ambion, RNAsin from Promega) that stabilize the RNA fraction. 
     Multiple maternal samples may be collected. For example, maternal samples can be collected each trimester, or monthly for a period during the course of pregnancy (e.g., months 3-8). When indicated, maternal samples may be collected more frequently. For example, gestational age or time to delivery may be monitored frequently (e.g., biweekly) as a method for monitoring fetal health. 
     As another example, a woman identified at 24 weeks as at risk of preterm delivery may elect biweekly assays to monitor risk. In cases in which intervention to avoid preterm delivery (e.g., progesterone supplementation) has been used, a maternal sample may be obtained after the initiation of the intervention to assess whether the intervention has changed the maternal expression profile. Remarkably, methods of the invention may be used to accurately discriminate women at risk of preterm delivery up to two months in advance of labor. See Example 6. In some embodiments of the invention a maternal sample is obtained more than 28 days prior to the preterm delivery. In some embodiments of the invention a maternal sample is obtained more than 45 days prior to the preterm delivery. In some embodiments a maternal sample is obtained after the second month and prior to the eighth month of pregnancy. In some embodiments a maternal sample is obtained during the second trimester of pregnancy In some embodiments a maternal sample is obtained during the third trimester of pregnancy. As discussed above, in many cases a maternal sample may be obtained and assayed more than once during the course of a pregnancy. 
     3.2 Isolation of cfRNA 
     Cell-free RNA can be isolated from a maternal sample using techniques well known in the art. See Example 1 below. Isolation of cfRNA from blood or blood fractions is described in Qin et al.,  BMC Res. Notes.,  26; 6:380 (2013) and Mersy et al.,  Clin. Chem.,  61(12)1515-23 (2015), both of which are incorporated herein by reference. Kits for isolating cfRNA from blood are known and are commercially available (e.g., PaxGene Blood RNA kit (Qiagen, Catalog No. 762164). Kits for isolating cfRNA from plasma/serum are known and are commercially available (e.g., Plasma/Serum RNA Purification Kit from Norgen Biotek Corporation, Canada, Catalog No.: 56900 and Quick-cfRNA™ Serum &amp; Plasma from Zymo Research, Catalog No.: R1059; NextPrep Magnazol cfRNA Isolation Kit (Bioo Scientific); Quick-cfRNA™ Serum &amp; Plasma Kit (Zymo Research), and the QIAamp® Circulating Nucleic Acid Kit (Qiagen). 
     Isolation of cfRNA from urine has been described (see, e.g., Zhao et al., 2015,  Int J. Cancer,  1; 136(11):2610-5, incorporated herein by reference, describing use of cfRNA for identification of biomarkers and monitoring disease status). Kits for isolating cfRNA from urine are known and are commercially available (e.g., Urine Cell Free Circulating RNA Purification Kit from Norgen Biotek Corporation, Canada, Catalog No.: 56900). 
     3.3 Quantification of cfRNA Transcripts 
     Quantification of specific transcripts from a cell free RNA sample can be accomplished in a variety of ways including, but not limited to, array-based methods, amplification-based methods (e.g., RT-qPCR), and high-throughput sequencing (RNA-Seq). The methods of the invention are not limited to a particular method of quantitation. 
     3.3.1 RT-qPCR Assays 
     RT-qPCR assays are described in Example 1, below. Briefly, RNA is transcribed into complementary DNA (cDNA) by reverse transcriptase from total RNA or messenger RNA (mRNA). Alternatively, cDNA is generated using template-specific primers specific for selected RNA transcripts (e.g., one of more of SEQ ID NOS:1-19). The cDNA is then used as the template for the qPCR reaction. 
     RT-qPCR can be performed in a one-step or a two-step assay. One-step assays combine reverse transcription and PCR in a single tube and buffer, using a reverse transcriptase along with a DNA polymerase. One-step RT-qPCR only utilizes sequence-specific primers. In two-step assays, the reverse transcription and PCR steps are performed in separate tubes, with different optimized buffers, reaction conditions, and priming strategies (such as random primers, oligo-(dT) or sequence specific primers in the reverse transcription followed by sequence specific primers in the qPCR step. As described above, it will be apparent that reference to RT-qPCR herein includes either a one or two step RT-qPCR assay. 
     RT-qPCR can be performed using various buffers and optimizations. See Example 1 below. Isolation of cfRNA from blood and subsequent analysis by RT-qPCR is known in the art (for example, see US Patent Publication No.: 20140199681, incorporated herein by reference). Kits for performing one step RT-qPCR are known and are commercially available (e.g., TaqPath™ 1-step RT-qPCR Master Mix, CG (Thermo Fisher Scientific, Catalog No. A15299). Kits for performing two step RT-qPCR are known and are commercially available (e.g., Maxima First Strand cDNA Synthesis Kit for RT-qPCR (Thermo Fisher Scientific, Catalog No. K1641). 
     3.3.2 RNA-Seq Assays 
     RNA-Seq (RNA-sequencing) assays also known as whole transcriptome shotgun sequencing uses next-generation sequencing (NGS) to reveal the presence and quantity of RNA in a sample at a given point in time (see, Zhong et al.  Nat. Rev. Gen.  10 (1): 57-63 (2009), incorporated herein by reference). RNA-Seq assays are described in Example 1, below. RNA-Seq facilitates the ability to look at changes in gene expression over time or differences in gene expression in different groups or treatments (see, Maher et al.  Nature.  458 (7234): 97-101 (2009), incorporated herein by reference). 
     The following sets forth an exemplary method to analyze cfRNAs isolated from a maternal body fluid sample. Briefly, cfRNAs are isolated from a maternal sample, for example using sequence specific primers, oligo(dT) or random primers to generate cDNA molecules. In one approach cDNA is generated using template-specific primers specific for selected RNA transcripts (e.g., corresponding to genes listed in TABLES 1 and 2; one of more of SEQ ID NOS:1-19). The cDNA molecules can be fragmented and optimized such that sequencing linkers are added to the 3′ and 5′ ends of the cDNA molecules to produce a sequencing library. Fragmentation is typically not needed for cfRNA. The optimized cDNAs are then sequenced using an NGS sequencing platform. Suitable kits for amplifying cDNA and analyzing sequencing products in accordance with the methods of the invention include, for example, the Ovation™ RNA-Seq System (NuGen). Other methods for preparing RNA-Seq libraries for use with a sequencing platform are known such as Podnar et al., 2014, “Next-Generation Sequencing RNA-Seq Library Construction”  Curr Protoc Mol Biol.  2014 Apr. 14; 106:4.21.1-19. doi: 10.1002/0471142727.mb0421s106; Schuierer et al., 2017, “A comprehensive assessment of RNA-Seq protocols for degraded and low-quantity samples.  BMC Genomics.  2017 Jun 5; 18(1):442. doi: 10.1186/s12864-017-3827-y; Hrdlickova R, 2017, RNA-Seq methods for transcriptome analysis, Wiley  Interdiscip Rev RNA.  2017 January; 8(1). doi: 10.1002/wrna.1364), all of which are incorporated herein by reference. 
     Sequencing libraries suitable for use with RNA-Seq assays can include cDNAs derived from cfRNAs isolated from a maternal sample. It will also be apparent that the sequencing libraries can include cDNAs derived from other RNA species (e.g., miRNAs) that may have been collected during total RNA isolation rather than a cfRNA isolation procedure. Accordingly, either a partial or complete transcriptome analysis can be performed on the RNA content obtained from the maternal sample. In one embodiment, it is preferred that only cfRNAs obtained from the maternal sample are used as the input material for preparing cDNAs suitable for RNA-Seq. 
     3.4 Profile Panels 
     The inventors have discovered that certain combinations of gene products are of particular use in practicing the invention. That is, certain combinations of gene products have been identified as sufficient or preferred for providing accurate estimates of gestational age, time to delivery or predicting likelihood of preterm delivery. For example, as described in Example 4, a subset of 9 placental genes provided more predictive power for estimating gestational age or time to delivery than a larger gene panel. 
     It will be appreciated that, although certain features of panels are discussed in this section, the invention is not limited to these particular described embodiments. It also will be understood that although this section describes panels by reference to cfRNA transcript expression, panels based on expression levels of circulating proteins encoded by the those gene subsets may also be used to determine gestational age or time to delivery and identify women at risk of preterm delivery. See Section 4, below. 
     In some approaches, multiple different profile panels are used during the course of a woman&#39;s pregnancy. For example, a first profile panel may be used in the second trimester and a different profile panel may be used in the third trimester. 
     3.4.1 Profile Panels for Determining Gestational Age or Time to Delivery 
     In one aspect, the invention provides a method for estimating gestational age or time to delivery of a fetus by analyzing a maternal sample to determine an expression profile of placental genes (e.g., cfRNA or protein encoded by a placental gene). Suitable panels may be selected based on the information provided in this disclosure. In one embodiment the panel includes one, at least 2, or at least 3 placental genes. In some embodiments, the profile panel can include at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 placental genes. In some embodiments, the profile panel can include exactly 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 placental genes. In some embodiments the profile panel includes fewer than 100 genes, e.g., fewer than 100 placental genes, sometimes fewer than 50 placental genes, sometimes fewer than 20 placental genes, sometimes fewer than 15 placental genes, sometimes fewer than 10 placental genes, and sometimes fewer than 5 placental genes. 
     In some embodiments the expression level of each of the placental genes in the profile panel changes during the course of pregnancy. See Examples below. Thus, in one embodiment, the expression level of at least one placental gene in the panel is higher in the first trimester compared to the third trimester. In some embodiments the expression levels of most or all placental genes in the panel are higher in the first trimester compared to the third trimester. In some embodiments, the expression level of at least one placental gene is lower in the first trimester compared to the third trimester. In some embodiments the expression levels of most or all placental genes in the panel are lower in the first trimester compared to the third trimester 
     In some embodiments at least one placental gene is selected from genes in TABLE 1. In some embodiments all of the placental genes in a profile panel are genes listed TABLE 1. 
     In some embodiments the expression profile includes at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, or 9 genes selected from CGA [SEQ ID NO:1], CAPN6 [SEQ ID NO:2], CGB [SEQ ID NO:3], ALPP [SEQ ID NO:4], CSHL1 [SEQ ID NO:5], PLAC4 [SEQ ID NO:6], PSG7 [SEQ ID NO:7], PAPPA [SEQ ID NO:8], and LGALS14 [SEQ ID NO:9]. In some embodiments the expression profile includes 1, 2, 3, 4, 5, 6, 7, 8, or 9 genes selected from CGA [SEQ ID NO:1], CAPN6 [SEQ ID NO:2], CGB [SEQ ID NO:3], ALPP [SEQ ID NO:4], CSHL1 [SEQ ID NO:5], PLAC4 [SEQ ID NO:6], PSG7 [SEQ ID NO:7], PAPPA [SEQ ID NO:8], and LGALS14 [SEQ ID NO:9]. In one approach the set of placental genes includes at least one gene other than CGA and CGB. In one approach, the profile panel comprises from three (3) to nine (9) cfRNAs selected from SEQ ID NOS:1-9. 
     In one embodiment gestational age is determined using a profile panel profile of 9 genes: CGA, CAPN6, CGB, ALPP, CSHL1, PLAC4, PSG7, PAPPA, and LGALS14. We trained several distinct models on subpopulations of women (i.e., nulliparous or multiparous women, women carrying male or female fetuses) to determine the importance of the 9 genes that compose the transcriptomic signature identified. Training 4 distinct models for women carrying male or female fetuses and nulliparous or multiparous women revealed that 2 of the 9 genes identified in the main text were sufficient to (CGA, CSHL1) or female (CGA, CAPN6) fetuses and multiparous (CGA, CSHL1) women. However, all 9 genes were necessary to optimally predict time until delivery for nulliparous women, highlighting the importance of the transcriptomic signature identified. In some embodiments of the invention the panel comprises CGA and CSHL1 or CGA and CAPN6. 
     The nine transcripts used to predict gestational age were weighted by the model in the following order of importance (from most to least): CGA, CAPN6, CGB, ALPP, CSHL1, PLAC4, PSG7, PAPPA, and LGALS14. Thus, in some embodiments the determined level of expression for individual genes are given different weights (or coefficients) when compared to expression in a reference profile. For example, when all 9, or a subset comprising fewer than 9 genes in this group (e.g., 2, 3, 4, 5, 6, 7 or 8) expression values for each gene are ranked CGA&gt;CAPN6&gt;CGB&gt;ALPP&gt;CSHL1&gt;PLAC4&gt;PSG7&gt;PAPPA&gt;LGALS14. 
     In one embodiment the panel includes one, at least 2, or at least 3 genes from TABLE 1. In some embodiments, the profile panel can include at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 genes from TABLE 1. In some embodiments, the profile panel can include exactly 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 genes from TABLE 1. In some embodiments the profile panel includes fewer than 100 genes, sometimes fewer than 50 genes, sometimes fewer than 20 genes, sometimes fewer than 15 genes, sometimes fewer than 10 genes, and sometimes fewer than 5 genes. In certain approaches the profile panel comprises a number of genes in the range 1-100 genes, 1-50 genes, 1-25 genes, 3-100 genes, 3-50 genes, 3-25 genes, or 3-10 genes. 
     In some versions the placental genes are selected from genes in TABLE 1. In some embodiments, the placental genes are selected from CGA, CAPN6, CGB, ALPP, CSHL1, PLAC4, PSG7, PAPPA, and LGALS14. In some embodiments, the genes include at least one gene other than CGA. In some embodiments, the genes include at least two, three, four, five, six, seven or eight genes other than CGA. In some embodiments, the genes include at least one gene other than CGB. In some embodiments, the genes include at least two, three, four, five, six, seven or eight genes other than CGB. In some embodiments, the genes include at least one gene other than CGA and CGB. In some embodiments, the method includes determining the expression profile for three (3) to nine placental genes. 
     3.4.2 Profile Panels for Determining Risk of Preterm Delivery 
     In one aspect, the invention provides a method for estimating risk of preterm delivery by analyzing a maternal sample to determine an expression profile. In one embodiment, the profile panel used for such a determination comprises one or more cfRNA transcripts with higher expression levels in a preterm population than in a term population. In one embodiment, a preterm population refers to a set of women who delivered a fetus prior to 37 weeks gestational age. In another embodiment, a preterm population refers to women who delivered a fetus prior to 33 weeks gestational age. In another embodiment, a preterm population refers to women who delivered a fetus prior to 29 weeks gestational age. In yet another embodiment, a preterm population refers to women who delivered a fetus between 12 and 33 weeks gestational age. In another embodiment, a preterm population refers to a set of women who delivered a fetus between 16 and 29 weeks gestational age. In an embodiment, a preterm population refers to a set of women who delivered a fetus between 16 and 33 weeks gestational age. As noted above, one preterm population used in the Examples consisted of women who delivered a fetus prior to 29 weeks gestational age and this population (or subpopulations thereof) is preferred for making reference profiles characteristic of high risk of prematurity. The Examples also show that biomarkers discovered in a population of women who delivered a fetus prior to 29 weeks are applicable in a population of women who delivered a fetus prior to 33 weeks gestational age. 
     In one approach the profile panel includes 1 or more, preferably 3 or more, genes listed in TABLE 2. 
     In one approach the profile panel includes three (3) or more genes are selected from the ten transcript panel CLCN3 [SEQ ID NO:10], DAPP1 [SEQ ID NO:11], POLE2 [SEQ ID NO:12], PPBP [SEQ ID NO:13], LYPLAL1 [SEQ ID NO:14], MAP3K7CL [SEQ ID NO:15], MOB1B [SEQ ID NO:16], RAB27B [SEQ ID NO:17], RGS18 [SEQ ID NO:18], and TBC1D15 [SEQ ID NO:19]. In one approach the profile panel comprises three (3) or more genes. In one approach the profile panel comprises three (3) or more genes selected from SEQ ID NOS:10-19. In one approach the profile panel comprises exactly three (3) genes selected from SEQ ID NOS:10-19. In some embodiments the panel comprises only genes selected from SEQ ID NOS:10-19. For example, in various embodiments, the profile panel will comprise the following combinations: (i) CLCN3, DAPP1, POLE2; (ii) DAPP1, POLE2, PPBP; (iii) POLE2, PPBP, LYPLAL1; (iv) PPBP, LYPLAL1, MAP3K7CL; (v) LYPLAL1, MAP3K7CL, MOB1B; (vi) MAP3K7CL, MOB1B, RAB27B; (vii) MOB1B, RAB27B, RGS18; and (viii) RAB27B, RGS18, TBC1D15. It will be appreciated that the full list of combinations of 3 genes selected from SEQ ID NOS:10-19 is easily generated, and this paragraph is intended to convey possession of each said combination of 3 genes. 
     In one approach the profile panel includes three (3) or more genes are selected from the seven transcript panel CLCN3 [SEQ ID NO:10], DAPP1 [SEQ ID NO:11], PPBP [SEQ ID NO:13], MAP3K7CL [SEQ ID NO:15], MOB1B [SEQ ID NO:16], RAB27B [SEQ ID NO:17], and RGS18 [SEQ ID NO:18]. In one approach the profile panel comprises three (3) or more genes. In one approach the profile panel comprises three (3) or more genes selected from SEQ ID NOS:10, 11, 13, and 15-18. In one approach the profile panel comprises exactly three (3) genes selected from SEQ ID NOS: 10, 11, 13, and 15-18. In some embodiments the panel comprises only genes selected from SEQ ID NOS: 10, 11, 13, 15, and 16-18. 
     In one approach the profile panel comprises exactly three genes selected from TABLE 2. In one approach the profile panel comprises exactly three genes selected from SEQ ID NO:10-19. In one approach the profile panel comprises exactly three genes selected from SEQ ID NOS: 10, 11, 13, 15, and 16-18. 
     The seven transcripts used to identify women at elevated risk or preterm delivery were weighted by the model in the following order of importance (from highest to lowest): RAB27B&gt;PPBP&gt;DAPP1&gt;RGS18&gt;(MOB1B, MAP3K7CL, and CLCN3), where MOB1B, MAP3K7CL, and CLCN3 are equally ranked. Thus, in some embodiments the determined level of expression for individual genes are given different weights (or coefficients) when compared to expression in a reference profile. For example, when all 7, or a subset comprising fewer than 7 genes in this group (e.g., 2, 3, 4, 5, 6) expression values for each gene are ranked): RAB27B&gt;PPBP&gt;DAPP1&gt;RGS18&gt;(MOB1B, MAP3K7CL, and CLCN3). 
     In one aspect, the invention provides a method for determining risk of preterm delivery by analyzing a maternal sample to determine an expression profile of a set of genes (e.g., cfRNA or protein) listed in TABLE 2, such as SEQ ID NOS: 10, 11, 13, 15, and 16-18. In one embodiment the panel includes one, at least 2, or at least 3 genes from TABLE 2. In some embodiments, the profile panel can include at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 genes from TABLE 2. In some embodiments, the profile panel can include exactly 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 genes from TABLE 2. In some embodiments the profile panel includes fewer than 100 genes, sometimes fewer than 50 genes, sometimes fewer than 20 genes, sometimes fewer than 15 genes, sometimes fewer than 10 genes, and sometimes fewer than 5 genes. In certain approaches the profile panel comprises a number of genes in the range 1-100 genes, 1-50 genes, 1-25 genes, 3-100 genes, 3-50 genes, 3-25 genes, or 3-10 genes. In one approach at least one of the genes in the profile panel does not listed in FIG. 3A and/or FIG. 3B and/or FIG. 4 of US Patent Publication No. 2013/0252835. 
     In one approach a maternal sample is obtained at a specified week of pregnancy and the maternal expression profile is compared to a time matched reference profile, wherein the time matched reference profile is characteristic of a full-term pregnancy profile at the specified week of pregnancy. In one approach a maternal sample is obtained at a specified trimester (e.g, first, second or third trimester) of pregnancy and the maternal expression profile is compared to a time matched reference profile, wherein the time matched reference profile is characteristic of a full-term pregnancy profile at the specified trimester of pregnancy. Significant deviations of the maternal profile from the reference profile is indicative that the woman as at elevated risk of preterm delivery. It will be immediately apparent that, in an alternative approach, a maternal sample is obtained at a specified week of pregnancy and the maternal expression profile is compared to a time matched reference profile, wherein the time matched reference profile is characteristic of a preterm pregnancy profile at the specified week of pregnancy. Significant similarities between the maternal profile and the reference profile is indicative that the woman as at elevated risk of preterm delivery. In one approach a machine learning model is used to compare the maternal profile and the reference profile. 
     4. ILLUSTRATIVE METHODS AND EMBODIMENTS USING CIRCULATING PROTEIN EXPRESSION 
     4.1 Isolation Of Proteins from Maternal Blood or Urine 
     Proteins can be isolated from a maternal sample using methods well known in the art. In one appropach total protein is from a maternal blood fraction or urine and assayed for the presence and/or quantity of particular proteins. In one approach an assay is carried out using a protein fraction (e.g., a fraction enriched for protein(s) of interest. In one approach an assay is carried out using one or more purified proteins. Isolation and fractionation of proteins can be performed using fractionation by molecular weight, protein charge, solubility/hydrophobicity, protein isoelectric point (pI), affinity purification (e.g., using a an antiligand, such as an antibody or aptamer, specific from a protein among other methods. Kits for isolating proteins from blood are known and are commercially available (e.g., Total Protein Assay Kit from ITSIBiosciences, Catalog No.: K-0014-20). Kits for isolating proteins from plasma/serum are known and are commercially available (e.g., Antibody Serum Purification Kit (Protein A) from Abcam, Catalog No.: ab109209). Kits for isolating protein and RNA from the sample are also known (e.g., Protein and RNA Isolation System (PARIS) from Thermo Fisher Scientific, Catalog No. AM1921). 
     4.2 Detecting Proteins from a Maternal Sample 
     Specific proteins from a maternal sample can be identifed and/or quantified using well know methods, including enzyme-linked immunoadsorbent assay (ELISA); radioimmunoassay (RA) (see, e.g., Anthony et al.,  Ann. Clin. Biochem.,  34:276-280 (1997) describing detection of low levels of protein undetectable using comparable ELISA conditions, incorporated herein by reference); proximity ligation and proximity extension assays (see, e.g., US Pat. Pub. Nos. 20170211133; 20160376642; 20160369321; 20160289750: 20140194311; 20140170654; 20130323729; and 20020064779, incorporated herein by reference), protein binding arrays (e.g., antibody or aptamer arrays), mass spectroscopy (see, e.g., Han, X. et al.(2008), incorporated herein by reference. Mass Spectrometry for Proteomics. Current Opinion in Chemical Biology, 12(5), 483-490. http://doi.org/10.1016/j.cbpa.2008.07.024; Serang, O et al (2012). A review of statistical methods for protein identification using tandem mass spectrometry. Statistics and Its Interface, 5(1), 3-20, incorporated herein by reference). Any suitable method may be used. 
     Protein binding arrays may be used to detect and quantitate proteins, including but not limited to antibody based arrays and aptamer based arrays (see, e.g., Gold L, et al. (2010) Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery. PLoS ONES(12): e15004. https://doi.org/10.1371/journal.pone.0015004, incorporated herein by reference). An antibody array (also known as antibody microarray) is a specific form of protein array. In this technology, a collection of capture antibodies are fixed on a solid surface such as glass, plastic, membrane, or silicon chip, and the interaction between the antibody and its target antigen is detected (see, e.g., U.S. Pat. Nos. 4,591,570; 4,829,010; and 5,100,777, all of which are incorporated herein by reference). Antibody arrays can be used to detect protein expression from various biological fluids including serum, plasma, urine and cell or tissue lysates (see, Knickerbocker T., MacBeath G. Detecting and Quantifying Multiple Proteins in Clinical Samples in High-Throughput Using Antibody Microarrays. In: Wu C. (eds) Protein Microarray for Disease Analysis. Methods in Molecular Biology (Methods and Protocols), vol 723. Humana Press (2011), incorporated herein by reference). 
     Kits for performing antibody arrays are known and are commercially available (e.g., custom designed antibody arrays or predetermined antibody arrays from RayBiotech, Norcross, Ga.). 
     5. STATISTICAL ANALYSIS 
     A maternal expression profile may be compared with a reference profile(s) in a variety of ways. In one approach, a comparison between two data sets is performed to determine whether one data set differs or is similar to another data set, e.g., to within statistical significance. In one embodiment, a first data set can comprise a maternal expression profile, and a second data set comprises a reference profile, where the first and second data sets include one or more data points (for example, median values) for gene expression data for one or more genes, collected over one or more time points during pregnancy (e.g., once a week or once a trimester during the course of the pregnancy). In some embodiments, the second data set comprises a plurality of data points from a preterm maternal sample or a maternal sample having a known gestational age. 
     Accordingly, a maternal data set can be a measured value of an expression level of one or more genes, where the expression level can be determined from individual expression values for each of the genes, e.g., as an average, weighted average, or median of the individual expression levels. In other embodiments, the individual expression levels can be treated as different dimensions of a multi-dimensional data point, e.g., for use in clustering. For determining a gestational age or time to delivery, the comparison can be between a measured expression level(s) of a maternal sample and the reference expression level(s) of each of a plurality of reference having different known gestational ages, thereby identifying a group or representative data point that is closest (e.g., least difference in a distance between the measured expression level(s) and the reference expression level(s)). The known gestational age of the closest reference sample (or representative data point of a group of reference samples all having a same gestational age) can be used as the gestational age or time to delivery of the maternal sample. Such a comparison can be performed by comprising the measured expression level(s) to a gestational function that is determined from the reference samples, e.g., a linear function that defines a functional relationship between the expression level(s) (e.g., in a multi-dimensional space when individual expression levels correspond to different dimensions or in a 2D-plot when individual expression levels are combined to provide a single metric). 
     In embodiments where a discrimination is made between term and preterm samples, the comparison can involve determining whether the measured expression level(s) are more similar to preterm reference level(s) or term reference level(s). Such a comparison can involve determining which cluster of reference levels is closest to the measured expression level(s). One or more values may be used for determining whether the measured expression level(s) are sufficiently close (e.g., as measured by a distance or a weight distance where differences along one dimension are weighted differently) for the measured level(s) to be considered part of either cluster of term or preterm samples. An indeterminate classification may result if the expression level(s) are not sufficiently close. A threshold can be used to determine whether the measured expression levels are sufficiently close to reference expression levels of a term or preterm population. A threshold can be selected based on a desired sensitivity and specificity, as will be apparent to one skilled in the art. 
     To determine the reference level(s), a set of training samples can be labeled with different classifications, e.g., term or preterm. Then, the reference levels can be chosen as being representative of a classification or as values that separate the different classifications, e.g., as cutoffs for assigning different classifications to a new sample. A machine learning technique can analyze different expression levels of different genes to determine which set of expression levels (features) provide the best discrimination for an optimized set of reference levels. A tradeoff between specificity and sensitivity can be optimized, e.g., by a ROC (receiver operating characteristic) curve. In some embodiments, a plurality of training samples, each labeled as preterm or full-term, can be obtained. In some embodiments, training samples are labeled as nulliparous, multiparous women, carrying male fetus, carrying female fetus, or the like. One or more measured expression levels for the panel of genes can be obtained for each of the plurality of training samples. Using the machine learning technique (e.g., by optimizing a cost function as defined by the model), the one or more reference expression levels can be iteratively adjusted to increase a number of the training samples that are classified correctly as a result of comparing the one or more measured expression levels to the one or more reference expression levels. 
     In some aspects, the first and second data sets can be analyzed to establish relative differences or similarities (e.g., fold increase or fold decrease) between the data sets (e.g., the expression level(s) of the data sets). Such a procedure can be performed when a single expression level is determine for a panel of genes. In another aspect, a pairwise comparison of expression level(s) at each time point for each gene across the duration of pregnancy can be used to identify which reference level(s) are most similar, where each set of reference level(s) can correspond to a different gestational age. In some embodiments, the pairwise comparison (e.g., pairwise between expression levels of different genes and/or between reference level(s) at different times) can include statistical analysis via a range of statistical methodologies, including but not limited to Fisher&#39;s exact test, Wilcox rank test, permutation test, linear regression, generalized linear models and quasi-likelihood tests coupled with the appropriate multiple hypothesis correction (e.g., Benjamini Hochberg). 
     In one embodiment, differentiating gene activity (e.g., between preterm and term maternal samples, see Example 1 and  FIGS.  11 A- 11 D ) across the pregnancy can include using a quantile adjusted conditional maximum likelihood method, a generalized linear model (GLM) likelihood ratio test, and/or a quasi-likelihood F-test implemented in R using the edgeR software (Bioconductor, available at https://bioconductor.org/packages/release/bioc/html/edgeR.html). 
     In another aspect, a sample data set can be analyzed using a random forest model (see, e.g., Chen and Ishwaran,  Genomics,  99:323-329 (2012), incorporated herein by reference) that was generated using the second data set. See Examples. Random forest is a form of machine learning that selects training sets randomly for building multiple models (e.g., decision trees or regression models) and uses the outputs of this ensemble of models to determine a final output (e.g., via majority voting for a term/preterm classification or an average when determining gestational age or time to delivery). Each model can have the same or different features (e.g., expression levels of genes), but have different reference levels as determined from the different training sets that are randomly selected. It will be recognized that other techniques of machine learning can be used to compare two data sets, including but not limited to, support vector machines, elastic net, lasso or neural networks. It will also be apparent that machine learning models (e.g., supervised machine learning; see, for example Mohri et al. (2012)  Foundations of Machine Learning,  The MIT Press, incorporated herein by reference) can be developed to account for particular attributes of a population such as ethnicity and that multiple models can be prepared based on different needs (e.g., an Eastern European model versus a North African model). 
     In one aspect, a machine learning model (e.g., to predict gestational age or time to delivery) can be prepared as follows: 
     (1) Curate a labeled training set (e.g., where gestational age of each sample is known); 
     (2) Iterate through selecting features of interest (e.g., recursive feature selection); 
     (3) Build a regression model (e.g., random forest) based on the selected features; and 
     (4) Select a regression model and feature subset using cross validation data (e.g., by withholding part of the training set and determining how accurately the regression model evaluated the withheld data). 
     In one embodiment, once the regression model is prepared, it can be saved and used for future data interpretations. In other embodiments, a single regression model can be determined, e.g., by fitting a line or a curve to a set of measured expression level(s) that are measured at known gestational ages. The regression model can be considered a gestational function, e.g., when a model (e.g., a linear or non-linear function) is fit to expression levels of a plurality of calibration samples having measured expression levels and of which a gestational age is known. Accordingly, the comparison of the maternal expression profile to the reference profile can be performed by comparing the maternal expression profile to a gestational function that provides a gestational age based on an input of one or more expression levels. 
     In another aspect, the first and second data sets can be analyzed using SAMS (Scoring Algorithm of Molecular Subphenotypes) available at http://statweb.stanford.edu/˜tibs/SAM/ (see, Tusher et al.,  PNAS,  98:5116-5121 (2001), incorporated herein by reference). SAMS is a classification algorithm of gene expression data generated from the calculation of two scores (e.g., an up score and a down score). In one embodiment, a maternal expression profile data set of the instant invention (e.g., cfRNAs) can be compared to a reference expression profile data set and a maternal sample having an up score above the median value (as compared to the reference expression profile) and a down score above the median value (as compared to the reference expression profile) can be classified as statistically significant (see., e.g., Herazo-Maya,  Lancet Respir Med,  September 20, (2017) doi:org/10.1016/52213-2600(17)30349-1 and Dinu et al.,  BMC Bioinformatics,  8:242 (2007), both incorporated herein by reference). Other evaluations of a first data set and a second data set using SAMS can be performed according to the SAMS user manual (available at http://www-stat.stanford.edu/˜tibs/SAM/sam.pdf). 
     Various additional statistical analyses exist for the comparison of a first and second data set directed to gene expression data (e.g., preterm data set versus a maternal sample) including for example, methods set forth by Efron and Tibshirani (On Testing the Significance of Sets of Genes.  Ann Appl. Stat.,  1. 107-129 (2007) and Zhao et al. (Gene expression profiling predicts survival in conventional renal cell carcinoma, PLOS Medicine, 3. E13. 13. 10.1371/journal.pmed.0030013. (2006), both incorporated herein by reference). 
     As discussed above, maternal expression profiles may be compared to reference profiles and a measure of similarity or difference may be made. In one approach, comparing a maternal expression profile to a reference profile includes compiling gene expression data (e.g., the number or relative number of transcripts of a specified cfRNA sequence on a computer-readable medium) and processing said data on said computer to identify degrees of similarity and difference between said profiles. 
     6. MEDICAL INTERVENTIONS FOR WOMEN AT RISK OF PRETERM DELIVERY 
     Women identified as at risk for preterm delivery may elect medical interventions (e.g., progesterone supplementation, cervical cerclage), behavioral changes (smoking cessation), or ultrasound imaging to monitor and reduce the likelihood of preterm delivery or to extend the pregnancy for as long as possible. See Newnham et al. “Strategies to Prevent Preterm Birth.”  Frontiers in Immunology  5 (2014):584, incorporated herein by reference. Progesterone may be used to treat and/or prevent the onset of preterm labor in women identified as at risk for preterm delivery. In some embodiments, a pregnant woman may be administered an amount of progesterone, e.g., as a vaginal gel, that is sufficient to prolong gestation by delaying the shortening or effacing of cervix. The administration can be as infrequent as weekly, or as often as 4 times daily. Antibiotic treatment (amoxicillin, ampicillin, erythromycin, azithromycin, and cephalosporin) is indicated in some women with premature rupture of the membranes (PROM), a precursor of premature delivery, and may be administered to women identified as at risk for preterm delivery. When a woman is identified as at risk of preterm delivery the medical provider may recommend an ultrasound examination at least once per four week period, biweekely, or weekly. 
     7. THERANOSTIC AND PROGNOSTIC USES OF THE INVENTION FOR WOMEN AT RISK OF PRETERM DELIVERY 
     In some embodiments, the methods described herein are used for theranosis. In one approach a first maternal expression profile is obtained from a woman at risk of preterm delivery at a first point in time, medically appropriate steps (e.g., medical interventions) are initiated or carried out, and then a second maternal expression profile is obtained from the woman at a second point in time. Each maternal expression profile is compared to an appropriate reference profile (e.g., time matched, population matched, etc.). If the difference between the second maternal expression profile and the appropriate corresponding reference profile is less than the difference between the first maternal expression profile and its appropriate corresponding reference profile this is an indication that the steps carried out have a beneficial therapeutic effect. In some cases, the first and second maternal expression profiles are compared to the same reference profile. In one approach the process is carried out without any medical intervention, in which case a spontaneous improvement may be observed. 
     In some embodiments, the methods described herein are used for prognosis. It is believed that certain maternal expression profiles are indicative of particular prognoses. For example, certain maternal expression profiles may be used to estimate time until preterm delivery (absent intervention). Reference profiles for this purpose can be generated from sub-populations grouped by specific pregnancy outcomes (dates of prematurity), by genetic risk, or by phenotypic factors such as age and previous pregnancy history. The methods disclosed herein may also be used for identifying and monitoring fetuses having congenital defects; in some cases the methods may be used to inform decisions about in utero treatment. Maternal expression profiles can be used to estimate time to delivery and gestational age for the fetus, and the results used for providing advice or treatment for either the mother or the fetus. Similarly, with appropriately chosen genes such profiles can be used to estimate the risk of adverse events such as preterm delivery. 
     8. COMPUTER IMPLEMENTED METHODS &amp; DATABASE OF REFERENCE VALUES 
     Methods of the invention may be implemented using a computer-based system. As used herein, “a computer-based system” refers to the hardware means, software means, and data storage means used to analyze the information of the present invention. The minimum hardware of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means, and data storage means. A skilled artisan can readily appreciate that any one of the currently available computer-based system are suitable for use in the present invention. The data storage means may comprise any manufacture comprising a recording of the present information as described above, or a memory access means that can access such a manufacture. 
     In some embodiments, a database comprising reference profiles is used in methods of the invention. In some embodiments, a database comprising expression data from a plurality of women, and optionally different subpopulations of women, is provided. Accordingly, aspects of the invention provide systems and methods for the use and development of a database. In some approaches the database is used in combination with an algorithm that enables generation of new reference profiles selected based on characteristics of an individual woman. 
     Any of the computer systems mentioned herein may utilize any suitable number of subsystems. In some embodiments, a computer system includes a single computer apparatus, where the subsystems can be the components of the computer apparatus. In other embodiments, a computer system can include multiple computer apparatuses, each being a subsystem, with internal components. A computer system can include desktop and laptop computers, tablets, mobile phones and other mobile devices. 
     A computer system can include a plurality of the same components or subsystems, e.g., connected together by external interface, by an internal interface, or via removable storage devices that can be connected and removed from one component to another component. In some embodiments, computer systems, subsystem, or apparatuses can communicate over a network. In such instances, one computer can be considered a client and another computer a server, where each can be part of a same computer system. A client and a server can each include multiple systems, subsystems, or components. 
     Aspects of embodiments can be implemented in the form of control logic using hardware circuitry (e.g. an application specific integrated circuit or field programmable gate array) and/or using computer software with a generally programmable processor in a modular or integrated manner. As used herein, a processor can include a single-core processor, multi-core processor on a same integrated chip, or multiple processing units on a single circuit board or networked, as well as dedicated hardware. Based on the disclosure and teachings provided herein, a person of ordinary skill in the art will know and appreciate other ways and/or methods to implement embodiments of the present invention using hardware and a combination of hardware and software. 
     Any of the software components or functions described in this application may be implemented as software code to be executed by a processor using any suitable computer language such as, for example, Java, C, C++, C#, Objective-C, Swift, or scripting language such as Perl or Python using, for example, conventional or object-oriented techniques. The software code may be stored as a series of instructions or commands on a computer readable medium for storage and/or transmission. A suitable non-transitory computer readable medium can include random access memory (RAM), a read only memory (ROM), a magnetic medium such as a hard-drive or a floppy disk, or an optical medium such as a compact disk (CD) or DVD (digital versatile disk), flash memory, and the like. The computer readable medium may be any combination of such storage or transmission devices. 
     The databases may be provided in a variety of forms or media to facilitate their use. “Media” refers to a manufacture that contains the expression information of the present invention. The databases of the present invention can be recorded on computer readable media, e.g. any medium that can be read and accessed directly by a computer (e.g., an internet database). Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media. One of skill in the art can readily appreciate how any of the presently known computer readable media can be used to create a manufacture comprising a recording of the present database information. “Recorded” refers to a process for storing information on computer readable medium, using any such methods as known in the art. Any convenient data storage structure may be chosen, based on the means used to access the stored information. A variety of data processor programs and formats can be used for storage, e.g. word processing text file, database format, etc. 
     Such programs may also be encoded and transmitted using carrier signals adapted for transmission via wired, optical, and/or wireless networks conforming to a variety of protocols, including the Internet. As such, a computer readable medium may be created using a data signal encoded with such programs. Computer readable media encoded with the program code may be packaged with a compatible device or provided separately from other devices (e.g., via Internet download). Any such computer readable medium may reside on or within a single computer product (e.g. a hard drive, a CD, or an entire computer system), and may be present on or within different computer products within a system or network. A computer system may include a monitor, printer, or other suitable display for providing any of the results mentioned herein to a user. 
     Any of the methods described herein may be totally or partially performed with a computer system including one or more processors, which can be configured to perform the steps. Thus, embodiments can be directed to computer systems configured to perform the steps of any of the methods described herein, potentially with different components performing a respective step or a respective group of steps. Although presented as numbered steps, steps of methods herein can be performed at a same time or at different times or in a different order. Additionally, portions of these steps may be used with portions of other steps from other methods. Also, all or portions of a step may be optional. Additionally, any of the steps of any of the methods can be performed with modules, units, circuits, or other means of a system for performing these steps. 
     9. PRIMERS, PROBES, AND COMPOSITIONS 
     Primers and probes that specifically hybridize to or amplify cfRNA from placental genes (including genes in TABLE 1) and other informative genes (including genes in TABLE 1 and TABLE 2) may be used in the practice of aspects of the invention. In particular, useful primers and probes include those that specifically hybridize to or amplify SEQ ID NOS: 1-19. These primers and probes are used for amplification (including multiplex PCR, multiplex RT-qPCR, or other amplification methods), for reverse transcription, for construction of sequencing libraries (e.g., RNA-seq libraries), for addition of adaptor sequences, for hybrid capture of RNAs of interest, for construction nucleic acid arrays, for primer extension and for other uses known to the practitioner with knowledge of the art. It is well within the ability of persons of ordinary skill in the art to design probes and primers for their intended uses, taking into account methods of amplification (e.g., addition of adaptors or universal primers), target sequence composition, base composition, avoiding artifacts such as primer dimer formation, as well as the fragmented nature of cfRNA. 
     For example, it is within the ability of persons of ordinary skill in the art to use SEQ ID NOS:1-19 to design primers, primers pairs, and probes that are specific for each gene and work for their intended purposes (e.g., use in a multiplex reaction). It will be appreciated that for each RNA transcript there are many different primers and combinations of primers that can amplify at least a portion of the transcript. A person of skill in the art can therefore design primer combinations to amplify informative sequences of any of SEQ ID NOS:1-19 or any combination thereof, as well as other gene sequences identified in TABLES 1 and 2. Exemplary primers and probes are described in TABLES 3-5. Probes may be nucleic acid probes, such as RNA or DNA probes. Primers or probes may be immobilized (e.g., for capture based enrichment) or detectably labeled (e.g., with fluorescent, enzymatic, or chemiluminescent moieties or the like). 
     9.1 Gestational Age or Time to Delivery Compositions 
     In one aspect, the invention provides primers for multiplex amplification of at least 3 and not more than 50, optionally no more than 25, optionally no more than 10 genes, selected from genes in TABLE 1. In some embodiments, the invention provides primers for multiplex amplification of at least 3 mRNA transcripts provided in TABLE 1. In another embodiment, the invention provides primers for multiplex amplification of any combination of at least 3 mRNA transcripts selected from SEQ ID NOS:1-9. In one embodiment, the primers are for multiplex amplification, wherein the primers comprise at least one pair, and optionally three or more primer pairs. Exemplary primer pairs are provided in TABLE 3. In another embodiment, the primers for multiplex amplification comprise at least three and no more than 100 primer pairs, optionally no more than 50, optionally no more than 25, optionally no more than 10 primer pairs selected from any of the primer pairs provided in TABLE 3. 
     In a related aspect, the invention provides compositions comprising primer(s) or primer pair(s) as described above. The composition may be an admixture. The composition may be a solution. The composition may additionally contain one or more of (a) maternal cfRNA, (b) buffer, (c) enzymes (e.g., one or a combination of reverse transcriptase, DNA polymerase, RNA or DNA ligase), (d) dNTPs. 
     In one aspect a composition is provided, comprising (1) cfRNAs with cfRNA sequences corresponding to at least 2 genes in TABLE 1, or amplicons of, or cDNAs from, said cfRNA sequences and (2) primers for amplifying said cfRNA sequences or amplicons or cDNAs, or probes for detecting said cfRNA sequences or amplicons or cDNAs, with the proviso that the composition does not comprise primers for amplifying more than a threshold number of different genes, amplicons or cDNAs; and does not comprise probes for detecting more than the threshold number of different cfRNA sequences or amplicons or cDNAs. In one embodiment the composition does not comprise cfRNAs with cfRNA sequences corresponding to more than the a threshold number of different genes from the human genome, or amplicons of, or cDNAs from more than the threshold number of different genes. In some embodiments the threshold number is 200. In some embodiments the threshold number is 150. In some embodiments the threshold number is 100. In some embodiments the threshold number is 50. In some embodiments the threshold number is 25. 
     In a related aspect, the invention provides nucleic acid arrays comprising primer(s), primer pair(s), or probes as described above. 
     9.2 Preterm Risk Compositions 
     In one aspect, the invention provides primers for multiplex amplification of at least 3 and no more than 100 genes, optionally no more than 50, optionally no more than 25, optionally no more than 10 genes, selected from genes in TABLE 2. In some embodiments, the invention provides primers for multiplex amplification of at least 3 mRNA transcripts provided in TABLE 2 (i.e., RefSeq identifiers). In another embodiment, the invention provides primers for multiplex amplification of any combination of at least 3 mRNA transcripts selected from SEQ ID NOS:10-19, or, alternatively at least 3 mRNA transcripts selected from SEQ ID NOS: 10, 11, 13, and 15-18. In one embodiment, the primers are for multiplex amplification, wherein the primers comprise at least one pair, and optionally three or more primer pairs. Exemplary primer pairs are provided in TABLE 3. In another embodiment, the primers for multiplex amplification comprise at least three and no more than 100 primer pairs, optionally no more than 50, optionally no more than 25, optionally no more than 10 pairs selected from any of the primer pairs provided in TABLE 3. 
     In a related aspect, the invention provides compositions comprising primer(s) or primer pair(s) as described above. The composition may be an admixture. The composition may be a solution. The composition may additionally contain one or more of (a) maternal cfRNA, (b) buffer, (c) enzymes (e.g., reverse transcriptase, DNA polymerase, RNA or DNA ligase), (d) dNTPs. 
     In a related aspect, the invention provides kits comprising primer(s) or primer pair(s) as described above packaged together. In one approach, a mixture of different primers are combined in a single mixture. In another approach, primers specific for individual cfRNAs are packaged together in separate vials. The kit may additionally contain one or more of (a) maternal cfRNA, (b) buffer, (c) enzymes (e.g., reverse transcriptase, DNA polymerase, RNA or DNA ligase), (d) dNTPs. 
     In one aspect a composition is provided, comprising (1) cfRNAs with cfRNA sequences corresponding to at least 2 genes in TABLE 2, or amplicons of, or cDNAs from, said cfRNA sequences and (2) primers for amplifying said cfRNA sequences or amplicons or cDNAs, or probes for detecting said cfRNA sequences or amplicons or cDNAs, with the proviso that the composition does not comprise primers for amplifying more than a threshold number of different genes, amplicons or cDNAs; and does not comprise probes for detecting more than the threshold number of different cfRNA sequences or amplicons or cDNAs. In one embodiment the composition does not comprise cfRNAs with cfRNA sequences corresponding to more than the a threshold number of different genes from the human genome, or amplicons of, or cDNAs from more than the threshold number of different genes. In some embodiments the threshold number is 200. In some embodiments the threshold number is 150. In some embodiments the threshold number is 100. In some embodiments the threshold number is 50. In some embodiments the threshold number is 25. 
     In a related aspect, the invention provides nucleic acid arrays comprising primer(s) or primer pair(s) as described above. 
     10. METHODS 
     This section describes implementation of the methods for determination of gestational age and risk of preterm delivery. Examples in this section are intended as illustrations and are in no sense limiting. 
     In one approach a maternal sample(s) is collected, frozen, and shipped to a centralized laboratory for analysis. In one approach methods of the invention are carried out in a local medical facility (e.g., hospital lab) optionally using a kit for isolation of cfRNA, production of cDNA, qPCR and/or sequencing. In one approach the kit includes reagent for cfRNA isolation. The use of a standardized kit is advantageous in ensuring uniformity of sample collection, cfRNA isolation, and analysis by qPCR or transcriptome sequencing. The kit may contain reagents for cfRNA, production of cDNA, qPCR and/or sequencing as well as primers or probes described herein for determining expression levels of cfRNA transcripts or combinations of transcripts described herein. In one approach cfRNA, cDNA, or a library is produced and shipped to a centralized laboratory for analysis. 
     In one approach a maternal sample(s) is collected and an expression profile is determined using a distributed system including client systems and server systems communicating over a computer network server-client, frozen, and shipped to a centralized laboratory for analysis. The server system may comprise databases of reference profiles and may receive data (e.g., expression profile information) from a client system. The expression profile information from the patient is compared to the reference profile using a computer product, e.g., comprising a computer readable medium storing a plurality of instructions for controlling a computer system to perform a method of the invention. the method of any one of the preceding claims. The databases of reference profiles may be produced using the machine learning approaches described herein. Advantageously, as expression profiles from individual patients is collected that information may be used as training data. This may be particularly useful when training and validation data are collected from demographically distinct patient populations (e.g., populations identified by age, race or ethnicity, geographical location, or other criteria). 
     Patient expression profiles will be most useful when they are tied to particular outcomes (e.g., term delivery or preterm delivery) or gestational age at birth. Thus, in one aspect the invention involves (1) collecting cfRNA from a pregnant woman one or multiple times during pregnancy, determining an expression profile using the cfRNA (i.e., an expression profile corresponding to a set of genes identified herein, e.g., genes from TABLE 1, TABLE 2, or TABLE 6 or combinations or subsets described herein); and recording the expression profile, e.g., on a suitable non-transitory computer readable medium; and then (2) determining the delivery date for the woman, categorizing the delivery as term or preterm (and if preterm, by how many days) or otherwise characterizing the outcome of the pregnancy, and (3) associating the information in (2) with the expression profiles in (1), e.g., by linking the information and expression profile(s) in the computer readable medium. 
     Determination of Gestational Age 
     In one approach a method performed using a computer for estimating gestational age of a fetus is provided comprising: (a) obtaining one or more expression profiles from a maternal sample of a pregnant woman carrying a fetus, wherein the expression profile(s) corresponds to the expression of cfRNA transcripts from a first panel of genes; (b) comparing, using a computer system, the expression profile(s) to one or more reference profile(s) characteristic of a defined gestational age(s) to estimate the gestational age of the fetus, wherein the reference profile(s) characteristic of the defined gestational age(s) are determined using a machine learning model that analyzes first training samples that are cfRNA expression profiles labeled with a defined gestational age; (c) updating, using the computer system, the reference profile(s) by: (1) receiving second training samples, wherein the second training samples are cfRNA expression profiles labeled with a defined gestational age, and (2) iteratively adjusting the reference profile(s) via a machine learning model to increase the number of the first and second training samples that are classified correctly. The reference profiles can form a line or curve or be discrete values. In some embodiments the first panel of genes comprises any combination of genes disclosed herein as predictive of gestational age, including placental genes, placental genes listed in Table 1, and at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, or 9 genes selected from CGA [SEQ ID NO:1], CAPN6 [SEQ ID NO:2], CGB [SEQ ID NO:3], ALPP [SEQ ID NO:4], CSHL1 [SEQ ID NO:5], PLAC4 [SEQ ID NO:6], PSG7 [SEQ ID NO:7], PAPPA [SEQ ID NO:8], and LGALS14 [SEQ ID NO:9]. 
     Also provided is a computer system comprising: (a) a database comprising reference profile(s), each including a level of expression in a population of pregnant women of cfRNA transcripts corresponding to a first panel of genes and corresponding to a defined gestational age; (b) a user interface configured to interact with a client computer over a network and to receive expression profile(s) including the level of expression in a pregnant woman carrying a fetus of cfRNA transcripts corresponding to the first panel of genes; and (c) one or more processors configured to analyze the reference profile and expression profile, including comparing the reference profile(s) and expression profile(s) to determine gestational age of the fetus; and (d) a network interface that transmits the gestational age of the fetus to the client computer. In one embodiment the the reference profile(s) and expression profile(s) comprise expression levels of a panel of cfRNAs in any combination disclosed herein, including transcripts from placental genes; placental genes listed in Table 1; and at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, or 9 genes selected from CGA [SEQ ID NO:1], CAPN6 [SEQ ID NO:2], CGB [SEQ ID NO:3], ALPP [SEQ ID NO:4], CSHL1 [SEQ ID NO:5], PLAC4 [SEQ ID NO:6], PSG7 [SEQ ID NO:7], PAPPA [SEQ ID NO:8], and LGALS14 [SEQ ID NO:9]. 
     Risk of Preterm Delivery 
     In one approach a method performed using a computer for assessing risk of preterm delivery by a pregnant woman is provided comprising: (a) obtaining one or more expression profiles from a maternal sample of a pregnant woman, wherein the expression profile(s) corresponds to the expression of a plurality of cfRNA transcripts from a first panel of genes; (b) comparing, using a computer system, the expression profile(s) to one or more reference profile(s) characteristic of a woman with (a) a high risk of preterm delivery or (b) a low risk of preterm delivery, or characteristic of a woman with a defined length of pregnancy, wherein the reference profiles are determined using a machine learning model that analyzes first training samples that are cfRNA expression profiles preterm or full-term, or labeled with a length of pregnancy (c) updating, using the computer system, the reference profile(s) by: (1) receiving second training samples, wherein the second training samples are cfRNA expression profiles labeled as preterm or full-term or labeled with a length of pregnancy, and (2) iteratively adjusting the reference profile(s) via a machine learning model to increase the number of the first and second training samples that are classified correctly. The reference profiles can form a line or curve or be discrete values. In some embodiments the first panel of genes comprises any combination of any combination of genes disclosed herein as predictive of risk of premature delivery, including genes listed in Table 1, and at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, or 9 genes selected from CGA [SEQ ID NO:1], CAPN6 [SEQ ID NO:2], CGB [SEQ ID NO:3], ALPP [SEQ ID NO:4], CSHL1 [SEQ ID NO:5], PLAC4 [SEQ ID NO:6], PSG7 [SEQ ID NO:7], PAPPA [SEQ ID NO:8], and LGALS14 [SEQ ID NO:9] or at least least 2, at least 3, at least 4, at least 5, at least 6, or 7 genes selected from CLCN3 [SEQ ID NO:10], DAPP1 [SEQ ID NO:11], PPBP [SEQ ID NO:13], MAP3K7CL [SEQ ID NO:15], MOB1B [SEQ ID NO:16], RAB27B [SEQ ID NO:17], and RGS18 [SEQ ID NO:18]. In some embodiments the first panel of genes comprises at least one combination selected from (1) RGS18; DAPP1; PPBP; (2) RGS18; RAB27B; PPBP; (3) RGS18; MOB1B; PPBP; (4) RGS18; PPBP; MAP3K7CL; (5) RGS18; PPBP; CLCN3; (6) DAPP1; RAB27B; PPBP; (7) DAPP1; MOB1B; PPBP; (8) DAPP1; PPBP; CLCN3; (9) RAB27B; MOB1B; PPBP; (10) RAB27B; PPBP; MAP3K7CL; (11) RAB27B; PPBP; CLCN3; (12) MOB1B; PPBP; MAP3K7CL; and (13) MOB1B; PPBP; CLCN3. 
     For determining risk of preterm delivery maternal samples can be labeled “preterm” and “term”; or with the gestational age of the child at birth; or with the length of the pregnancy (e.g., week of delivery), combinations of these, or labels suitable for quantitatively or qualitatively distinguishing a full-term delivery from a preterm delivery. 
     Also provided is a computer system comprising: (a) a database comprising reference profile(s), each including a level of expression in a population of pregnant women of cfRNA transcripts corresponding to a first panel of genes and risk of preterm delivery; (b) a user interface interface configured to interact with a client computer over a network and to receive expression profile(s) including the level of expression in a pregnant woman of cfRNA transcripts corresponding to the first panel of genes; and (c) one or more processors configured to analyze the reference profile and expression profile, including comparing the reference profile(s) and expression profile(s) to determine the risk of preterm delivery; and (d) a network interface that transmits the risk of preterm delivery to the client computer. In some embodiments the reference profile(s) and expression profile(s) comprise expression levels of a panel of cfRNAs in any combination disclosed herein, including genes listed in Table 1 and at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, or 9 genes selected from CGA [SEQ ID NO:1], CAPN6 [SEQ ID NO:2], CGB [SEQ ID NO:3], ALPP [SEQ ID NO:4], CSHL1 [SEQ ID NO:5], PLAC4 [SEQ ID NO:6], PSG7 [SEQ ID NO:7], PAPPA [SEQ ID NO:8], and LGALS14 [SEQ ID NO:9] or at least least 2, at least 3, at least 4, at least 5, at least 6, or 7 genes selected from CLCN3 [SEQ ID NO:10], DAPP1 [SEQ ID NO:11], PPBP [SEQ ID NO:13], MAP3K7CL [SEQ ID NO:15], MOB1B [SEQ ID NO:16], RAB27B [SEQ ID NO:17], and RGS18 [SEQ ID NO:18]. 
     11. EXAMPLES 
     12.1 Example 1 
     Materials and Experimental Methods 
     Sample Collection 
     Blood samples from pregnant Danish women were collected weekly (high-resolution cohort) and at one time point during the second or third trimester from the University of Pennsylvania (preterm discovery cohort) and the University of Alabama at Birmingham (preterm validation cohort) under an Institutional Review Board-approved protocol. Women who participated in the study in Pennsylvania and Alabama were at elevated risk for spontaneous premature delivery. All women who delivered preterm except one patient from Pennsylvania (preeclampsia) experienced spontaneous preterm birth. As per the standard of care, all women with a history of preterm delivery received weekly progesterone injections. The blood samples were collected into EDTA-coated Vacutainer tubes (Becton Dickinson, NJ). Plasma was separated from blood using standard clinical blood centrifugation protocol. 
     Cell-Free RNA (cfRNA) Isolation 
     Cell-free RNA was extracted from 0.75-2 mL of plasma using Plasma/Serum Circulating RNA and Exosomal Purification kit (Norgen Biotek Corp, Canada, Catalog No. 42800). The residue of DNA was digested using Baseline-ZERO DNase (Epicentre, WI) and then cleaned by RNA Clean and Concentrator™-5 kit (Zymo Research, CA). The resulting RNA was eluted to 12 μl in elution buffer. 
     RT-qPCR Assay 
     RT-qPCR assays consist of two main reactions: reverse transcription/preamplification of extracted cfRNA and qPCR of pre-amplified cDNA. The primers for our gene panels were designed and synthesized by Fluidigm Corporation, CA (TABLE 3). Either 1-2 μl or 10 μl out of the 12 μl of total purified RNA was used for reverse transcription/preamplification reaction using the CellsDirect™ One-Step RT-qPCR Kit (Invitrogen, CA, Catalog No. 11753-100) and a pool of 96 primer pairs from TABLE 3. Preamplification was performed for 20 cycles and residual primers of the reaction were digested using exonuclease I treatment. Multiplex qPCR reactions of 96 samples for the 96 primer pairs were performed using 96×96 Dynamic Array Chip on BioMark System (Fluidigm Corp., CA). The BioMark Dynamic Array Chip loads individual samples (cDNA) and individual reagents (primer pairs) separately into wells on the Dynamic Array chip. The integrated fluidics circuit controllers push samples and reagents through channels until full; then coordinated releasing and closing of fluidic values allows mixing of samples and reagents into individual compartments within the chip. The 96×96 Dynamic Array Chip can simultaneously analyze up to 9,216 reactions. Threshold cycles (Ct values) of qPCR reactions were extracted using Fluidigm real-time PCR analysis software. 
     cfRNA-Seq Library Preparation 
     A cell-free RNA sequencing library was prepared by SMARTer Stranded Total RNAseq—Pico Input Mammalian kit (Clontech, CA, Catalog No. 634413) from 6 μl of eluted cfRNA according to the manufacturer&#39;s manual. Short read sequencing was performed on Illumina NextSeq™ (2×75 bp) platform (Illumina, CA) to the depth of more than 10 million reads per samples. 
     Statistical Analysis 
     cfRNA-Seq Differential Expression Analysis 
     28 samples (14 term and 14 preterm) cfRNA samples of the preterm discovery cohort were sequenced. The sequencing reads were mapped to human reference genome (hg38) using STAR aligner. Duplicates were removed by Picard and then unique reads were quantified using htseq-count. After preprocessing, 16 samples containing sequencing reads that mapped to more than 3000 genes were used for subsequent statistical analyses. Differentiating genes between term and preterm samples were identified using a quantile-adjusted conditional maximum likelihood method, a generalized linear model (GLM) likelihood ratio test, and a quasi-likelihood F-test implemented in R using the edgeR package. 
     RT-qPCR Sample Analysis 
     Raw C t  values were quantified in absolute terms. Absolute quantification estimated the transcript counts contained in each sample based on cycle thresholds for known quantities of ERCC ( FIG.  9   ). Estimated transcript counts were then adjusted for dilution, sample volume, and normalized by the volume of processed plasma. 
     Multivariate Random Forest Modeling 
     Recursive feature selection and model construction were performed in R using the caret package. Longitudinal data was smoothed using a 3-week centered moving average and divided into a 21 patient training set and a 10 patient validation set. Model selection was performed using 10-fold cross validation repeated 10 times. 
     Expected Delivery Date Estimation 
     Expected delivery dates were derived from random forest model predictions. Longitudinal data for this application were not smoothed using a centered moving average. For any given sampling period (second trimester (T2), third trimester (T3), or both (T2&amp;T3), time to delivery estimates were shifted to a specified reference time point and then averaged using the median to establish an expected delivery date. 
     Preterm Biomarker Candidate Selection and Validation 
     Absolute RT-qPCR values were normalized using a modified multiple of the median approach as applied in Rose and Mennuti ( Fetal Medicine, West J Med.,  1993; 159:312-317, incorporated herein by reference) that is both time and epidemiologically invariant, allowing for consistent comparisons across cohorts of different ethnicities. At-term patient medians were quantified by trimester on a cohort level for each gene. Biomarker discovery was performed using the combined criterion of an effect size and significance value threshold calculated using Hedges&#39; g and the Fisher exact test, respectively, as described in Sweeney et al. ( J. Pediatric Infect. Dis. Soc.,  2017, doi: 10.1093/jpids/pix021, incorporated herein by reference). Genes were considered significantly different between cohorts using an effect size threshold of 0.8 and a false discovery rate (FDR) of 5%. Candidate gene biomarkers were then tested in unique combinations of 3 to estimate their ability to detect both true and false positives. Combinations with a true positive rate of greater than 0.75 and a false positive rate less than 0.05 were selected for further validation using an independent cohort. The ROC curve was based on the fraction of biomarker combinations where all genes showed a fold increase of at least 2.5 over median expression. 
     11.2 Example 2 
     Longitudinal Data of Due Dates from Three Distinct Populations 
     We performed a high time-resolution study of normal human development by measuring cfRNA in blood from pregnant women longitudinally during each week of pregnancy. cfRNA provides a window into the phenotypic state of the pregnancy by providing information about gene expression in fetal, placental and maternal tissues. Koh et al. described using tissue-specific genes for direct measurement of tissue health and physiology, and that these measurements are concordant with the known physiology of pregnancy and fetal development at low time resolution (Koh et al.  PNAS,  Vol. 111, 20:7361-7366, (2014), incorporated herein by reference). Analysis of tissue-specific transcripts in the instant samples enabled us to follow fetal and placental development with high resolution and sensitivity, and also to detect gene-specific response of the maternal immune system to pregnancy. The data from the present study establishes a “clock” for normal human development and enables a direct molecular approach to establish time to delivery and gestational age using nine placental genes. We demonstrate that cfRNA samples from both the second and third trimesters of pregnancy can predict expected delivery date with comparable accuracy to ultrasound, creating the basis for a portable, inexpensive dating method. 
     We recruited 31 pregnant Danish women from the Danish National Biobank, each of whom agreed to give blood on a weekly basis, resulting in 521 total plasma samples to analyze ( FIG.  1 A ). All women delivered normally at term, defined as a gestational age at delivery of or greater than 37 weeks, and their medical records showed no unusual health changes during pregnancy (TABLE 8). Each sample was analyzed by highly multiplexed real time PCR using a panel of genes that were chosen to be specific to the placenta, fetal tissue, or the immune system. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                   
                   
                 Pennsylvania (n = 16) 
                 Alabama (n = 26) 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Denmark 
                 Preterm 
                 At-term 
                 Preterm 
                 At-term 
               
               
                 Demographics 
                 (n = 31) 
                 (n = 9) 
                 (n = 7) 
                 (n = 8) 
                 (n = 18) 
               
               
                   
               
               
                 Age (years ± SD) 
                 29.9 ± 3.2  
                   
                   
                 23.9 ± 2.8  
                 25.8 ± 4.4  
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Parity (% nulliparous) 
                 19  
                 (61.3) 
                   
                   
                 0  
                 (0) 
                 0  
                 (0) 
               
            
           
           
               
               
               
               
               
               
            
               
                 BMI (kg/m 2 , mean ± SD) 
                 22.1 ± 3.6 
                   
                   
                 28.9 ± 10.5 
                 28.6 ± 7.0  
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Ethnicity (% Hispanic) 
                 0  
                 (0) 
                   
                   
                 0  
                 (0) 
                 0  
                 (0) 
               
               
                 Caucasian (%) 
                 31  
                 (100) 
                   
                   
                 0  
                 (0) 
                 1  
                 (8) 
               
               
                 African-American (%) 
                 0  
                 (0) 
                   
                   
                 8  
                 (100) 
                 17  
                 (94) 
               
            
           
           
               
               
               
               
               
               
            
               
                 Gestational age at delivery 
                 40 ± 1.2 
                 26.7 ± 2.3 
                 39.4 ± 0.5 
                 30.8 ± 2.5 
                 38.7 ± 1.2 
               
               
                 (weeks, mean ± SD) 
                   
                   
                   
                   
                   
               
               
                 Mode of delivery 
                   
                   
                   
                   
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Spontaneous 
                 67.7 
                   
                   
                 7  
                 (88) 
                 16  
                 (29) 
               
               
                 Cesarean section 
                 12.9 
                   
                   
                 1  
                 (12) 
                 2  
                 (11) 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Gender (% male) 
                 14  
                 (45.2) 
                   
                   
                 5  
                 (63) 
                 10  
                 (58) 
               
            
           
           
               
               
               
               
               
               
            
               
                 Birth weight (kg, mean ± 
                 3.8 ± 0.6 
                   
                   
                 1.7 ± 0.7 
                 3.1 ± 0.4 
               
               
                 SD) 
               
               
                   
               
            
           
         
       
     
     11.3 Example 3 
     Gene Expression of Maternal, Placental and Fetal-Tissue Specific Genes in Maternal Plasma Samples from Normal Due Date Deliveries 
     Cell-free RNA was isolated from each of the Denmark cohort individuals blood samples as set forth in Example 1. RT-qPCR assays were performed on the isolated cfRNA essentially as set forth in Example 1. A primer pair for each of the genes set forth in  FIG.  9    was added to aliquots of the cfRNA samples and Ct values were calculated using appropriate controls. 
     Gene-specific inter-patient monthly averages±standard error of the mean (SEM) were plotted over the course of gestation ( FIG.  2 A ). The average time course of gene expression highlighted interesting behavior that differed by gene function ( FIGS.  2 A  and 4). Placental and fetal genes (blue and yellow) show a clear increase through the course of pregnancy with slightly different trajectories depending on the gene. Some of these genes plateau before delivery and one of them (CGB) decreases from a peak in the first trimester. Immune genes, which are dominated by the maternal immune system but may also include a fetal contribution, have a more complex interpretation but in general show changes in time with measurable baselines early in pregnancy and after delivery. We then calculated the correlation between gene values across all genes and all pregnancies ( FIG.  2 B ) and discovered that genes within each set (i.e. placental, immune, fetal) were highly correlated with each other. Moreover, we found that placental and fetal genes also showed a moderate degree of cross correlation, suggesting that placental cfRNA may provide an accurate estimate of fetal development and gestational age throughout pregnancy. 
     11.4 Example 4 
     Model for Prediction of Time to Delivery &amp; Comparison with Gold Standard 
     The results of the gene expression assays motivated us to apply a machine learning approach in order to build a model, which would predict gestational age or time to delivery from cfRNA measurements. We used a random forest model and were able to show that a subset of nine placental genes provided more predictive power than using the full panel of measured genes ( FIG.  5   ). Using these 9 genes (CGA, CAPN6, CGB, ALPP, CSHL1, PLAC4, PSG7, PAPPA, and LGALS14) we accurately predicted the time from sample collection until delivery (Pearson correlation r=0.91, P&lt;2.2×10 −16 ), which is an objective criterion independent of ultrasound-estimated gestational age ( FIG.  2 C ). Our model&#39;s performance improved significantly over the course of gestation (root mean squared error (RMSE)=6.0 (T1), 3.9 (T2), 3.3 (T3), 3.7 (PP) weeks). Remarkably, our model performed equally well (r=0.89, P&lt;2.2×10 −16 ) on a withheld cohort of 10 women during the validation stage (RMSE=5.4 (T1), 4.2 (T2), 3.8 (T3), 2.7 (PP) weeks) ( FIG.  2 D ). 
     We also built a separate model to predict gestational age (as estimated by ultrasound) and using the same nine placental genes, the model performed comparably well both on training (r=0.91, P&lt;2.2×10 −16 ) and validation data (r=0.90, P&lt;2.2×10 −16 ) ( FIGS.  6 A and  6 B ). 
     The random forest model selects placental genes as most predictive of time from sample collection until delivery and gestational age. Although several of these genes show similar time trajectories, their detection rate early on pregnancy varies, suggesting that redundancy may improve accuracy at early time points, when both placental and fetal cfRNA are low and lead to drop-out effects. As cfRNA increases during gestation, the accuracy of the model improves. This is in contrast with the efficacy of ultrasound dating, which relies on a constant fetal growth rate, an assumption that deteriorates over time (Savitz et al. 2002; Papageorghiou et al. 2016). 
     Further investigating drivers of the model reveals markers with known roles during pregnancy. CGA and CGB, the two main model drivers together with CAPN6, behave differently from other genes in the model. CGA and CGB are the two subunits of HCG, known to play a major role in pregnancy initiation and progression and involved in trophoblast differentiation (Jaffe et al. 1969). The trend observed for these two genes is compatible with what is known from protein levels during pregnancy (Cocquebert et al. 2012). Free CGB and PAPPA are also used as biochemical markers for at risk of Down Syndrome in the first trimester (Wald and Hackshaw 1997), and other genes selected by the model are related to trophoblast development (e.g., LGALS14, PAPPA). 
     We then used our model to estimate expected delivery date from samples taken during the second, third, or both trimesters ( FIG.  2 E ). We found that 32% (T2), 23% (T3), 45% (T2&amp;T3), and 48% (T1 Ultrasound) of patients delivered within one week of their expected delivery dates (TABLE 9). 
     
       
         
           
               
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                   
                 Δ(Observed-Expected delivery date) (%) 
               
            
           
           
               
               
               
               
               
               
            
               
                 Method 
                 &lt;−2 weeks 
                 −1 to −2 weeks 
                 ±1 week 
                 +1 to +2 weeks 
                 &gt;+2 weeks 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 cfRNA (T2) 
                 50 
                 18 
                 32 
                 0 
                 0 
               
               
                 cfRNA (T3) 
                 0 
                 6 
                 23 
                 29 
                 42 
               
               
                 cfRNA (T2 &amp; T3) 
                 19 
                 6 
                 45 
                 10 
                 20 
               
               
                 Ultrasound (T1) 
                 0 
                 26 
                 48 
                 23 
                 3 
               
               
                   
               
            
           
         
       
     
     Prior studies report that under normal circumstances it is possible to determine the week in which a woman may deliver with 57.8% accuracy using ultrasound and 48.1% using LMP (Savitz et al. 2002). Our results are not only comparable to ultrasound measurements at a fraction of the cost but also use a method that is more easily ported to resource challenged settings. 
     For gestational age prediction, we trained several distinct models on subpopulations of women (i.e., nulliparous or multiparous women, women carrying male or female fetuses) to determine the importance of the 9 genes that compose the transcriptomic signature identified. Training 4 distinct models for women carrying male or female fetuses and nulliparous or multiparous women revealed that 2 of the 9 genes identified in the main text were sufficient to predict time to delivery for women carrying male (CGA, CSHL1) (Root mean squared error (RMSE) of 5.43 and 4.80 in the second and third trimesters respectively) or female (CGA, CAPN6) fetuses (RMSE of 5.58 and 4.60 in the second and third trimesters respectively) and multiparous (CGA, CSHL1) women (RMSE of 5.22 and 4.56 in the second and third trimesters respectively). However, all 9 genes were necessary to predict time until delivery for nulliparous women (RMSE of 5.09 and 4.50 in the second and third trimesters respectively), highlighting the importance of the transcriptomic signature identified. The nine transcripts used to predict gestational age were weighted by the model in the following order of importance (from most to least): CGA, CAPN6, CGB, ALPP, CSHL1, PLAC4, PSG7, PAPPA, and LGALS14. See TABLE 10. 
                         TABLE 10                      7.70 (T1-multiparous),           5.09 (T2-nulliparous) vs 5.22 (T2-multiparous),           4.50 (T3-nulliparous) vs 4.56 (T3-multiparous), and           3.13 (PP-nulliparous) vs 4.24 (PP-multiparous) weeks.           5.58 (T2-female) vs 5.43 (T2-male),           4.60 (T3-female) vs 4.80 (T3-male), and           2.57 (PP-female) vs 2.83 (PP-male) weeks.                    
In summary, we have discovered a molecular clock of fetal development which reflects the roadmap of developmental gene expression in the placenta and fetus, and enables prediction of time to delivery, gestational age, and expected delivery date with comparable accuracy to ultrasound. Our method has several advantages to ultrasound, namely cost and applicability later during pregnancy. At a fraction of the cost of ultrasound, cfRNA measurements can be easily ported to resource challenged settings. Even in countries that regularly use ultrasound, cfRNA presents an attractive, accurate alternative to ultrasound, especially during the second and third trimesters, when ultrasound predictions deteriorate to 15 (T2) or 27 (T3) day estimates of delivery (Altman and Chitty 1997). We expect that this clock will also be useful for discovering and monitoring fetuses having congenital defects that can be treated in utero, which represents a rapidly growing part of maternal-fetal medicine.
 
     11.5 Example 5 
     Identification Of Differentially Expressed Genes Between Normal and Preterm Deliveries 
     While the first generation “clock” model is able to predict gestational age and time of delivery for a normal pregnancy, we were also interested in testing its performance on preterm delivery. We therefore used two separately recruited cohorts from communities at high risk for premature delivery recruited at the University of Pennsylvania and the University of Alabama at Birmingham to test performance on preterm pregnancies (see,  FIG.  1    and TABLE 1). We discovered that while the model validated performance on normal pregnancy (RMSE=4.3 weeks), it generally failed to predict time until delivery in preterm samples (RMSE=10.5 weeks) ( FIG.  7   ). This suggests that the model&#39;s content is reflective of the normal developmental program and may not account for the various outlier physiological events which may lead to preterm birth. In other words, from a molecular perspective, the premature fetus does not appear to have reached full gestation and therefore preterm birth is likely not caused by overmaturation signals from the fetus or placenta, which give the illusion of reaching full-term. This conclusion is supported by the observation that pharmacological agents designed to stop or slow down uterine contractions prevent a small number of preterm deliveries (Romero et al. 2014; Conde-Agudelo and Romero 2016). 
     To further investigate this question and develop a second generation “clock” model capable of predicting preterm delivery, we performed RNAseq, essentially as set forth in Example 1, on cfRNA obtained from plasma samples from term (n=7) and preterm (n=9) women collected from one of the preterm-enriched cohorts (Pennsylvania) (see,  FIG.  1    and TABLE 1) for genes, which may discriminate preterm from normal delivery. 
     Analysis of this RNAseq data suggested that nearly 40 genes could separate term from preterm with statistical significance (p&lt;0.001) (see,  FIG.  3 A  and  FIGS.  10 A- 10 D ). When recalculated to exclude one preeclamptic woman (see Examples) it was determined that 37 genes could separate term from preterm with statistical significance. 
     We then created a PCR panel with the highest scoring candidate preterm biomarkers and other immune and placental genes. We confirmed that the differential expression observed in RNAseq was also observed with this qPCR panel ( FIG.  8   ). 
     11.6 Example 6 
     Model for Prediction of Preterm Delivery 
     The top ten genes from this panel (CLCN3, DAPP1, POLE2, PPBP, LYPLAL1, MAP3K7CL, MOB1B, RAB27B, RGS18, TBC1D15) (FDR 5%, Hedge&#39;s g≥0.8) ( FIG.  3 B ), accurately classify 7 out of 9 preterm samples (78%) and misclassify only 1 of 26 at-term samples (4%) from both Pennsylvania and Denmark with a mean AUC of 0.87 ( FIG.  3 C ). 
     When used in combination, these ten genes also showed successful validation in an independent preterm-enriched cohort from Alabama, accurately classifying 4 out of 6 preterm samples (66%) and misclassifying 3 out of 18 at-term samples (17%) (see,  FIG.  1   ). 
     Moreover, this independent validation cohort shows that it is possible to discriminate preterm from term pregnancy up to 2 months in advance of labor with an AUC of 0.74 ( FIG.  3 C ). Several of the genes in the response signature were individually significantly more highly expressed in women who delivered preterm (FDR≤5%, Hedge&#39;s g≥0.8), demonstrating the robustness of their effect ( FIG.  3 B ). Our data suggests that the genes associated with spontaneous preterm birth are distinct from those found to be most predictive for gestational age and normal time to delivery. 
     In subsequent refinements we determined that one woman in the cohort experienced induced preterm birth due to preeclampsia rather than spontaneous preterm birth We removed the data points associated with her plasma sample. Rerunning the analysis with this sample removed yielded 7 transcripts (CLCN3, DAPP1, PPBP, MAP3K7CL, MOB1B, RAB27B, RGS18) as opposed to 10, that when used in combinations of 3 produced a true positive rate of greater than 75% and misclassified less than 5%. 
     As described in Example 7, below, we identified several subcombinations of the 7 transcripts that may be used to determine a woman&#39;s likelihood or risk of preterm delivery. Thus, in some approaches one or more of the following panels is used to assess the likelihood of full-term, or preterm, delivery: (1) RGS18; DAPP1; PPBP; (2) RGS18; RAB27B; PPBP; (3) RGS18; MOB1B; PPBP; (4) RGS18; PPBP; MAP3K7CL; (5) RGS18; PPBP; CLCN3; (6) DAPP1; RAB27B; PPBP; (7) DAPP1; MOB1B; PPBP; (8) DAPP1; PPBP; CLCN3; (9) RAB27B; MOB1B; PPBP; (10) RAB27B; PPBP; MAP3K7CL; (11) RAB27B; PPBP; CLCN3; (12) MOB1B; PPBP; MAP3K7CL; and (13) MOB1B; PPBP; CLCN3. 
     We found that PPBP, DAPP1, and RAB27B were all individually elevated in women who delivered preterm in both the Pennsylvania and Alabama cohorts (FDR≤5%, Hedge&#39;s g≥0.8), demonstrating the robustness of their effect. The ranking the weight order (from highest to lowest) is RAB27B&gt;PPBP&gt;DAPP1&gt;RGS18&gt;(MOB1B, MAP3K7CL, and CLCN3). 
     In summary, we have discovered and validated a set of biomarkers which enables prediction of time to delivery for patients at risk of preterm delivery. Furthermore, our preterm delivery model suggests that the physiology of preterm delivery is distinct from normal development, forming the basis for the first screening or diagnostic test for risk of prematurity. 
     11.7 Example 7 
     Gene Combinations Meeting the Criterion of 75% True Positive Rate and Less Than 5% False Positive Rate 
     Seven transcripts of interest RAB27B, PPBP, DAPP1, RGS18, MOB1B, MAP3K7CL, CLCN37 can be grouped in 35 unique combinations of genes. We filtered those combinations using the criterion of 75% true positive rate and less than 5% false positive rate. This yielded 13 combinations shown in TABLE 11. We generated an ROC curve to determine the which combinations predict risk of delivering preterm. 
                                 TABLE 11               Combination   Gene 1   Gene 2   Gene 3                   1   RGS18   DAPP1   PPBP        2   RGS18   RAB27B   PPBP        3   RGS18   MOB1B   PPBP        4   RGS18   PPBP   MAP3K7CL        5   RGS18   PPBP   CLCN3        6   DAPP1   RAB27B   PPBP        7   DAPP1   MOB1B   PPBP        8   DAPP1   PPBP   CLCN3        9   RAB27B   MOB1B   PPBP       10   RAB27B   PPBP   MAP3K7CL       11   RAB27B   PPBP   CLCN3       12   MOB1B   PPBP   MAP3K7CL       13   MOB1B   PPBP   CLCN3                    
Each of these 13 combinations of 3 genes may be used as a panel for assessing risk of preterm delivery. Thus, in some embodiments a panel comprising one or more of the following combination of genes is used to determine of the following panels Thus, in some approaches a panel comprising one or more of the following combinations of genes is used to assess the likelihood of full-term, or preterm, delivery: (1) RGS18; DAPP1; PPBP; (2) RGS18; RAB27B; PPBP; (3) RGS18; MOB1B; PPBP; (4) RGS18; PPBP; MAP3K7CL; (5) RGS18; PPBP; CLCN3; (6) DAPP1; RAB27B; PPBP; (7) DAPP1; MOB1B; PPBP; (8) DAPP1; PPBP; CLCN3; (9) RAB27B; MOB1B; PPBP; (10) RAB27B; PPBP; MAP3K7CL; (11) RAB27B; PPBP; CLCN3; (12) MOB1B; PPBP; MAP3K7CL; and (13) MOB1B; PPBP; CLCN3.
 
     11.8 Example 8 
     Body Mass Index (BMI) Does Not Affect Cell-Free RNA (cfRNA) Levels 
     We have tested for the effect of BMI on circulating cfRNA levels using estimated transcript counts of GAPDH per milliliter of plasma and found no significant difference between underweight (BMI&lt;18.5), normal weight (18.5≤BMI&lt;25), overweight (25≤BMI&lt;30), and obese (BMI≥30) individuals both before and after Bonferroni correction using a Wilcoxon rank sum test. 
     P-values for distinct tests of GAPDH levels before and after Bonferroni correction, respectively, were as follows: (1) underweight versus normal weight (P=0.58, 1), underweight versus overweight (P=0.12, 0.80), underweight versus obese (P=0.26, 1), normal weight versus overweight (P=0.06, 0.35), normal weight versus obese (P=0.16, 0.95), and overweight versus obese (P=0.72, 1). Similar results were obtained for placental-specific cfRNAs such as CAPN6, CGA, and CGB. 
     All comparisons were done within cohorts so that differences in BMI distribution between cohorts were not confounding. 
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     Rose, N. C., &amp; Mennuti, M. T. (1993). Maternal serum screening for neural tube defects and fetal chromosome abnormalities. The Western Journal of Medicine, 159(3), 312-317. 
     Savitz, D. A., Terry, J. W., Dole, N., Thorp, J. M., Siega-Riz, A. M., &amp; Herring, A. H. (2002). Comparison of pregnancy dating by last menstrual period, ultrasound scanning, and their combination. American Journal of Obstetrics and Gynecology, 187(6), 1660-1666. doi:10.1067/mob.2002.127601 
     Sweeney, T. E., Haynes, W. A., Vallania, F., Ioannidis, J. P., &amp; Khatri, P. (2017). Methods to increase reproducibility in differential gene expression via meta-analysis. Nucleic Acids Research, 45(1), e1. doi:10.1093/nar/gkw797 
     Wald, N. J., &amp; Hackshaw, A. K. (1997). Combining ultrasound and biochemistry in first-trimester screening for Down&#39;s syndrome. Prenatal Diagnosis, 17(9), 821-829. doi:10.1002/(SICI)1097-0223(199709)17:9&lt;821::AID-PD154&gt;3.0.CO; 2-5 
     Ward, K., Argyle, V., Meade, M., &amp; Nelson, L. (2005). The heritability of preterm delivery. Obstetrics and Gynecology, 106(6), 1235-1239. doi:10.1097/01.AOG.0000189091.35982.85 
     Whitworth, M., Bricker, L., &amp; Mullan, C. (2015). Ultrasound for fetal assessment in early pregnancy. Cochrane Database of Systematic Reviews, (7), CD007058. doi:10.1002/14651858.CD007058.pub3 
     Yefet, E., Kuzmin, O., Schwartz, N., Basson, F., &amp; Nachum, Z. (2017). Predictive Value of Second-Trimester Biomarkers and Maternal Features for Adverse Pregnancy Outcomes. Fetal Diagnosis and Therapy. doi:10.1159/000458409 
     York, T. P., Strauss, J. F., Neale, M. C., &amp; Eaves, L. J. (2009). Estimating fetal and maternal genetic contributions to premature birth from multiparous pregnancy histories of twins using MCMC and maximum-likelihood approaches. Twin Research and Human Genetics, 12(4), 333-342. doi:10.1375/twin.12.4.333 
     Zhang, G., et al. (2017). Genetic Associations with Gestational Duration and Spontaneous Preterm Birth. The New England Journal of Medicine, 377(12), 1156-1167. doi:10.1056/NEJMoa1612665 
     Rose and Mennuti ( Fetal Medicine, West J Med.,  1993; 159:312-317) 
     Sweeney et al. ( J. Pediatric Infect. Dis. Soc.,  2017, doi: 10.1093/jpids/pix021.) 
     13. TABLES 1-5 
       
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 PREDICTING TIME TO DELIVERY 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                   
                 Tissue 
                   
                   
               
               
                 Gene 
                 RefSeq 
                 Gene ID 
                 Specificity 
                 Tissue 
                 Function 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 CGA 
                 NM_001252383.1 
                 1081 
                 Yes 
                 Placenta 
                 Subunit of HCG 
               
               
                 CAPN6 
                 NM_014289.3 
                 827 
                 Yes 
                 Placenta 
                 Calcium-dependent 
               
               
                   
                   
                   
                   
                   
                 cysteine protease 
               
               
                 CGB 
                 NM_000737.3 
                 1082 
                 Yes 
                 Placenta 
                 Subunit of HCG 
               
               
                 LGALS14 
                 NM_020129.2 
                 56891 
                 Yes 
                 Placenta 
                 Carbohydrate 
               
               
                   
                   
                   
                   
                   
                 recognition 
               
               
                 PSG7 
                 NM_002783.2 
                 5676 
                 Yes 
                 Placenta 
                 Immunoglobin-like 
               
               
                   
                   
                   
                   
                   
                 proteins, known to be 
               
               
                   
                   
                   
                   
                   
                 released into maternal 
               
               
                   
                   
                   
                   
                   
                 circulation 
               
               
                 ALPP 
                 NM_001632.3 
                 250 
                 Yes 
                 Placenta 
                 Alkaline phosphatase 
               
               
                 CSHL1 
                 NM_001318.2 
                 1444 
                 Yes 
                 Placenta 
                 Growth control, located 
               
               
                   
                   
                   
                   
                   
                 at growth hormone 
               
               
                   
                   
                   
                   
                   
                 locus, expressed in 
               
               
                   
                   
                   
                   
                   
                 placental villi 
               
               
                 PAPPA 
                 NM_002581.3 
                 5069 
                 Yes 
                 Placenta 
                 Metalloproteinase which 
               
               
                   
                   
                   
                   
                   
                 cleaves insulin growth 
               
               
                   
                   
                   
                   
                   
                 factors that can then 
               
               
                   
                   
                   
                   
                   
                 bind IGF receptors 
               
               
                 PLAC4 
                 NM_182832.2 
                 191585 
                 Yes 
                 Placenta 
                 Expressed in placental 
               
               
                   
                   
                   
                   
                   
                 syncytiotrophoblasts, 
               
               
                   
                   
                   
                   
                   
                 associated with 
               
               
                   
                   
                   
                   
                   
                 preeclampsia and 
               
               
                   
                   
                   
                   
                   
                 trisomy 21 
               
               
                 ACTB 
                 NM_001101.3 
                 60 
                 No 
                   
                   
               
               
                 HSD3B1 
                 NM_000862.2 
                 3283 
                 Yes 
                 Placenta 
                   
               
               
                 S100A8 
                 NM_002964.4 
                 6279 
                 Yes 
                 Immune 
                 Immune indicates bone 
               
               
                   
                   
                   
                   
                   
                 marrow specificity 
               
               
                 HAL 
                 NM_002108.2 
                 15109 
                 No 
                   
                   
               
               
                 HSPB8 
                 NM_014365.2 
                 26353 
                 No 
                   
                   
               
               
                 VGLL1 
                 NM_016267.3 
                 51442 
                 Yes 
                 Placenta 
                   
               
               
                 S100A9 
                 NM_002965.3 
                 6280 
                 Yes 
                 Immune 
                 Immune indicates bone 
               
               
                   
                   
                   
                   
                   
                 marrow specificity 
               
               
                 ITIH2 
                 NM_002216.2 
                 3698 
                 Yes 
                 Liver 
                   
               
               
                 ANXA3 
                 NM_005139.2 
                 306 
                 Yes 
                 Immune 
                   
               
               
                 S100P 
                 NM_005980.2 
                 6286 
                 No 
                   
                   
               
               
                 KNG1 
                 NM_000893.3 
                 3827 
                 Yes 
                 Liver 
                   
               
               
                 CYP3A7 
                 NM_000765.3 
                 1551 
                 Yes 
                 Liver 
                   
               
               
                 CSH1 
                 NM_001317.5 
                 1442 
                 Yes 
                 Placenta 
                   
               
               
                 CAMP 
                 NM_004345.4 
                 820 
                 Yes 
                 Immune 
                 Immune indicates bone 
               
               
                   
                   
                   
                   
                   
                 marrow specificity 
               
               
                 OTC 
                 NM_000531.5 
                 5009 
                 Yes 
                 Liver 
                   
               
               
                 DCX 
                 NM_000555.3 
                 1641 
                 Yes 
                 Brain 
                   
               
               
                 FSTL3 
                 NM_005860.2 
                 10272 
                 Yes 
                 Placenta 
                   
               
               
                 CSH2 
                 NM_022644.3 
                 1443 
                 Yes 
                 Placenta 
                   
               
               
                 PLAC1 
                 NM_021796.3 
                 10761 
                 Yes 
                 Placenta 
                   
               
               
                 DEFA4 
                 NM_001925.1 
                 1669 
                 Yes 
                 Immune 
                 Immune indicates bone 
               
               
                   
                   
                   
                   
                   
                 marrow specificity 
               
               
                 FABP1 
                 NM_001443.1 
                 2168 
                 Yes 
                 Liver 
                   
               
               
                 SERPINA7 
                 NM_000354.5 
                 6906 
                 Yes 
                 Liver 
                   
               
               
                 FRZB 
                 NM_001463.3 
                 2487 
                 No 
                   
                   
               
               
                 SLC2A2 
                 NM_000340.1 
                 6514 
                 Yes 
                 Liver 
                   
               
               
                 LTF 
                 NM_001199149.1 
                 4057 
                 Yes 
                 Immune 
                 Immune indicates bone 
               
               
                   
                   
                   
                   
                   
                 marrow specificity 
               
               
                 FGA 
                 NM_000508.3 
                 2243 
                 Yes 
                 Liver 
                   
               
               
                 SLC4A1 
                 NM_000342.3 
                 6521 
                 Yes 
                 Immune 
                 Immune indicates bone 
               
               
                   
                   
                   
                   
                   
                 marrow specificity 
               
               
                 GNAZ 
                 NM_002073.2 
                 2781 
                 No 
                   
                   
               
               
                 ADAM12 
                 NM_003474.4 
                 8038 
                 Yes 
                 Placenta 
                   
               
               
                 GH2 
                 NM_022557.3 
                 2689 
                 Yes 
                 Placenta 
                   
               
               
                 PSG1 
                 NM_006905.2 
                 5669 
                 Yes 
                 Placenta 
                   
               
               
                 MMP8 
                 NM_002424.2 
                 4317 
                 Yes 
                 Immune 
                 Immune indicates bone 
               
               
                   
                   
                   
                   
                   
                 marrow specificity 
               
               
                 FGB 
                 NM_005141.4 
                 2244 
                 Yes 
                 Liver 
                   
               
               
                 ARG1 
                 NM_001244438.1 
                 383 
                 Yes 
                 Liver 
                   
               
               
                 MEF2C 
                 NM_001131005.2 
                 4208 
                 No 
                   
                   
               
               
                 HSD17B1 
                 NM_000413.2 
                 3292 
                 Yes 
                 Placenta 
                   
               
               
                 PSG4 
                 NM_002780.4 
                 5672 
                 Yes 
                 Placenta 
                   
               
               
                 PGLYRP1 
                 NM_005091.2 
                 8993 
                 Yes 
                 Immune 
                 Immune indicates bone 
               
               
                   
                   
                   
                   
                   
                 marrow specificity 
               
               
                 SLC38A4 
                 NM_018018.4 
                 55089 
                 Yes 
                 Liver 
                   
               
               
                 EPB42 
                 NM_000119.2 
                 2038 
                 Yes 
                 Immune 
                 Immune indicates bone 
               
               
                   
                   
                   
                   
                   
                 marrow specificity 
               
               
                 PTGER3 
                 NM_198717.1 
                 5733 
                 No 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 PREDICTING PRETERM DELIVERY 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                   
                 Tissue 
                   
                   
                   
               
               
                 Gene 
                 RefSeq 
                 Gene ID 
                 Specificity 
                 Tissue 
                 “Druggable?” 
                 Function 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 TBC1D15 
                 NM_001146214 
                 64786 
                 No 
                   
                 Yes - involved in 
                 Encodes Ras- 
               
               
                   
                   
                   
                   
                   
                 signalling 
                 like protein. 
               
               
                   
                   
                   
                   
                   
                   
                 Regulator of 
               
               
                   
                   
                   
                   
                   
                   
                 intracellular 
               
               
                   
                   
                   
                   
                   
                   
                 traffic 
               
               
                 RGS18 
                 NM_130782 
                 64407 
                 No 
                   
                 Yes - involved in 
                 Regulator of 
               
               
                   
                   
                   
                   
                   
                 signalling 
                 G-protein 
               
               
                   
                   
                   
                   
                   
                   
                 signaling 
               
               
                 DAPP1 
                 NM_001306151 
                 27071 
                 No 
                   
                 Yes - involved in 
                 B-cell receptor 
               
               
                   
                   
                   
                   
                   
                 signalling 
                 signaling 
               
               
                   
                   
                   
                   
                   
                   
                 pathway 
               
               
                 RAB27B 
                 NM_004163 
                 5874 
                 No 
                   
                 Yes - involved in 
                 Prenylated, 
               
               
                   
                   
                   
                   
                   
                 signalling 
                 membrane 
               
               
                   
                   
                   
                   
                   
                   
                 bound 
               
               
                   
                   
                   
                   
                   
                   
                 proteins 
               
               
                   
                   
                   
                   
                   
                   
                 involved in 
               
               
                   
                   
                   
                   
                   
                   
                 vesicular 
               
               
                   
                   
                   
                   
                   
                   
                 fusion and 
               
               
                   
                   
                   
                   
                   
                   
                 trafficking 
               
               
                 MOB1B 
                 NM_001244766 
                 92597 
                 No 
                   
                 Yes - involved in cell 
                 Kinase 
               
               
                   
                   
                   
                   
                   
                 cycle 
                 essential for 
               
               
                   
                   
                   
                   
                   
                   
                 spindle pole 
               
               
                   
                   
                   
                   
                   
                   
                 body 
               
               
                   
                   
                   
                   
                   
                   
                 duplicaiton 
               
               
                   
                   
                   
                   
                   
                   
                 and mitotic 
               
               
                   
                   
                   
                   
                   
                   
                 checkpoint 
               
               
                   
                   
                   
                   
                   
                   
                 regulation 
               
               
                 PPBP 
                 NM_002704 
                 5473 
                 Yes 
                 Immune 
                 Unclear 
                 Platelet 
               
               
                   
                   
                   
                   
                   
                   
                 dereived 
               
               
                   
                   
                   
                   
                   
                   
                 growth factor 
               
               
                 LYPLAL1 
                 NM_138794 
                 127018 
                 No 
                   
                 Unclear 
                 Unknown, 
               
               
                   
                   
                   
                   
                   
                   
                 links to 
               
               
                   
                   
                   
                   
                   
                   
                 childhood 
               
               
                   
                   
                   
                   
                   
                   
                 obesity and 
               
               
                   
                   
                   
                   
                   
                   
                 hypertension 
               
               
                 MAP3K7CL 
                 NM_001286617 
                 56911 
                 No 
                   
                 Unclear 
                 Unknown 
               
               
                 CLCN3 
                 NM_173872 
                 1182 
                 No 
                   
                 Probably not given 
                 Voltage-gated 
               
               
                   
                   
                   
                   
                   
                 its ubiquitous 
                 chloride 
               
               
                   
                   
                   
                   
                   
                 nature across cell 
                 channel 
               
               
                   
                   
                   
                   
                   
                 types 
                 present in all 
               
               
                   
                   
                   
                   
                   
                   
                 cell types 
               
               
                 POLE2 
                 NM_002692 
                 5427 
                 No 
                   
                 Yes - involved in cell 
                 Involved in 
               
               
                   
                   
                   
                   
                   
                 cycle 
                 DNA repair 
               
               
                   
                   
                   
                   
                   
                   
                 and 
               
               
                   
                   
                   
                   
                   
                   
                 replication 
               
               
                 CGB 
                 NM_000737.3 
                 1082 
                 Yes 
                 Placenta 
               
               
                 PKHD1L1 
                 NM_177531 
                 93035 
                 Yes 
                 Thyroid 
               
               
                 APLF 
                 NM_173545 
                 200558 
                 No 
               
               
                 DGCR14 
                 NR_134304 
                 8220 
                 Yes 
                 Testis 
               
               
                 MMD 
                 NM_012329 
                 23531 
                 Yes 
                 Fat 
               
               
                 VCAN 
                 NM_004385 
                 1462 
                 No 
               
               
                 P2RY12 
                 NM_022788 
                 64805 
                 Yes 
                 Brain 
               
               
                 RAB11A 
                 NM_004663 
                 8766 
                 No 
               
               
                 FRMD4B 
                 NM_015123 
                 23150 
                 No 
               
               
                 PLAC4 
                 NM_182832.2 
                 191585 
                 Yes 
                 Placenta 
               
               
                 ADAM12 
                 NM_003474.4 
                 8038 
                 Yes 
                 Placenta 
               
               
                 CYP3A7 
                 NM_000765.3 
                 1551 
                 Yes 
                 Liver 
               
               
                 VGLL1 
                 NM_016267.3 
                 51442 
                 Yes 
                 Placenta 
               
               
                 GH2 
                 NM_022557.3 
                 2689 
                 Yes 
                 Placenta 
               
               
                 CAPN6 
                 NM_014289.3 
                 827 
                 Yes 
                 Placenta 
               
               
                 PSG4 
                 NM_002780.4 
                 5672 
                 Yes 
                 Placenta 
               
               
                 RPL23AP7 
                 NR_024528 
                 118433 
                 No 
               
               
                 ANXA3 
                 NM_005139.2 
                 306 
                 Yes 
                 Immune 
               
               
                 HSPB8 
                 NM_014365.2 
                 26353 
                 No 
               
               
                 PKHD1L1 
                 NM_177531 
                 93035 
                 Yes 
                 Thyroid 
               
               
                 AVPR1A 
                 NM_000706 
                 552 
                 No 
               
               
                 KLF9 
                 NM_001206 
                 687 
                 No 
               
               
                 CSHL1 
                 NM_001318.2 
                 1444 
                 Yes 
                 Placenta 
               
               
                 PSG7 
                 NM_002783.2 
                 5676 
                 Yes 
                 Placenta 
               
               
                 CGA 
                 NM_001252383.1 
                 1081 
                 Yes 
                 Placenta 
               
               
                 PAPPA 
                 NM_002581.3 
                 5069 
                 Yes 
                 Placenta 
               
               
                 PSG1 
                 NM_006905.2 
                 5669 
                 Yes 
                 Placenta 
               
               
                 CSH2 
                 NM_022644.3 
                 1443 
                 Yes 
                 Placenta 
               
               
                 LGALS14 
                 NM_020129.2 
                 56891 
                 Yes 
                 Placenta 
               
               
                 KRT8 
                 NR_045962 
                 3856 
                 No 
               
               
                 CD180 
                 NM_005582 
                 4064 
                 No 
               
               
                 NFATC2 
                 NM_012340 
                 4773 
                 No 
               
               
                 PLAC1 
                 NM_021796.3 
                 10761 
                 Yes 
                 Placenta 
               
               
                 RAP1GAP 
                 NM_001145657 
                 5909 
                 No 
               
               
                 CAMP 
                 NM_004345.4 
                 820 
                 Yes 
                 Immune 
               
               
                 ENAH 
                 NM_001008493 
                 55740 
                 No 
               
               
                 CPVL 
                 NM_019029 
                 54504 
                 No 
               
               
                 ELANE 
                 NM_001972 
                 1991 
                 Yes 
                 Immune 
               
               
                 LTF 
                 NM_001199149.1 
                 4057 
                 Yes 
                 Immune 
               
               
                 PGLYRP1 
                 NM_005091.2 
                 8993 
                 Yes 
                 Immune 
               
               
                 FAM212B-AS1 
                 NR_038951 
                 100506343 
                 No 
               
               
                 Immune 
                 indicates 
                 bone 
                 marrow 
                 specificity 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Exemplary primer pairs. 
               
            
           
           
               
               
               
               
               
            
               
                   
                 SEQ 
                   
                   
                 SEQ 
               
               
                   
                 ID 
                   
                   
                 ID 
               
               
                 Gene 
                 NO: 
                 Forward Primer 
                 Reverse Primer 
                 NO: 
               
               
                   
               
               
                 ACTB 
                  20 
                 CCAACCGCGAGAAGATGAC 
                 TAGCACAGCCTGGATAGCAA 
                  21 
               
               
                   
               
               
                 ADAM12 
                  22 
                 TGAGAAAGGAGGCTGCATCA 
                 CTGCTGCAACTGCTGAACA 
                  23 
               
               
                   
               
               
                 AFP 
                  24 
                 GCCTCTTCCAGAAACTAGGAGAA 
                 GGGGCTTTCTTTGTGTAAGCAA 
                  25 
               
               
                   
               
               
                 ALPP 
                  26 
                 GACAGCTGCCAGGATCCTAA 
                 GTCTGGCACATGTTTGTCTACA 
                  27 
               
               
                   
               
               
                 ANXA1 
                  28 
                 AAGTGCGCCACAAGCAAA 
                 TGCCTTATGGCGAGTTCCA 
                  29 
               
               
                   
               
               
                 ANXA3 
                  30 
                 CAGCGGCAGCTGATTGTTAA 
                 CAGAGAGATCACCCTTCAAGTCA 
                  31 
               
               
                   
               
               
                 APLF 
                  32 
                 ACCCAGATGACTCCCACAAA 
                 CAAGGATTGGCTGCTGCTTA 
                  33 
               
               
                   
               
               
                 APOA4 
                  34 
                 AAGGCCGTGGTCCTGAC 
                 TCAGCTGGCTGAAGTAGTCC 
                  35 
               
               
                   
               
               
                 ARG1 
                  36 
                 GCAAGGTGGCAGAAGTCAA 
                 ATGGCCAGAGATGCTTCCA 
                  37 
               
               
                   
               
               
                 AVPR1A 
                  38 
                 GCGCCTTTCTTCATCATCCA 
                 GATGGTGATGGTAGGGTTTTCC 
                  39 
               
               
                   
               
               
                 BPI 
                  40 
                 TCCTGGAACTGAAGCACTCA 
                 GCAGCACAAGAATGGGTACA 
                  41 
               
               
                   
               
               
                 CALCB 
                  42 
                 CCCCTTCCTGGCTCTCAGTA 
                 GGTCTGGGCTGCTCTCCA 
                  43 
               
               
                   
               
               
                 CAMP 
                  44 
                 GGACAGTGACCCTCAACCA 
                 CAGCAGGGCAAATCTCTTGTTA 
                  45 
               
               
                   
               
               
                 CAPN6 
                  46 
                 TGGAAAGGTGGTGTGGAAAC 
                 GTCAGCTGGTGGTTGCTAA 
                  47 
               
               
                   
               
               
                 CCL20 
                  48 
                 TGATGTCAGTGCTGCTACTCC 
                 CTGTGTATCCAAGACAGCAGTCA 
                  49 
               
               
                   
               
               
                 CD160 
                  50 
                 CTCAGTTCAGGCTTCCTACA 
                 TCTTTTGGCACAAGGCTTAC 
                  51 
               
               
                   
               
               
                 CD180 
                  52 
                 CACAATAGAACCTTCAGCAGAC 
                 GAAAAGTGTCTTCATGTATCCAGTTA 
                  53 
               
               
                   
               
               
                 CD2 
                  54 
                 ATTCCAGCTTCAACCCCTCA 
                 ATGACTAGGTGCCTGGGAAC 
                  55 
               
               
                   
               
               
                 CD24 
                  56 
                 CCAACTAATGCCACCACCAA 
                 CGAAGAGACTGGCTGTTGAC 
                  57 
               
               
                   
               
               
                 CD5 
                  58 
                 CCCCTTGCCTACAAGAAGCTA 
                 TCCCGTTGGGCCAATCC 
                  59 
               
               
                   
               
               
                 CDK5R1 
                  60 
                 AGCAAGAACGCCAAGGACAA 
                 CGGCCACGATTCTCTTCCAA 
                  61 
               
               
                   
               
               
                 CEACAM6 
                  62 
                 AGATTGCATGTCCCCTGGAA 
                 GGGTGGGTTCCAGAAGGTTA 
                  63 
               
               
                   
               
               
                 CEACAM8 
                  64 
                 TATGCCTGCCACACCACTAA 
                 GCCAGGAGAACTTCCTTGTACTA 
                  65 
               
               
                   
               
               
                 CGA 
                  66 
                 TCAACCGCCCTGAACACA 
                 ACACCGACAATGTGACCAGAA 
                  67 
               
               
                   
               
               
                 CGB 
                  68 
                 AGCCTTCCAAGCCCATCC 
                 TGCGGATTGAGAAGCCTTTA 
                  69 
               
               
                   
               
               
                 CLCN3 
                  70 
                 CGTGGTCAGGATGGCTAGTA 
                 CCAATCGGCAGCAATGTCTA 
                  71 
               
               
                   
               
               
                 CNOT7 
                  72 
                 GTCCTCTGTGAAGGGGTCAAA 
                 TCTTCAGGCAAGTTAGAGTTGGTTA 
                  73 
               
               
                   
               
               
                 COL17A1 
                  74 
                 TGACAACCCAGAGCTCATCC 
                 GGACGCCATGTTGTTTGGAA 
                  75 
               
               
                   
               
               
                 COL21A1 
                  76 
                 CGTCCAGGTGTCAGAGGATTA 
                 ACCTTGTTCTCCAGGATACCC 
                  77 
               
               
                   
               
               
                 CPVL 
                  78 
                 TGAAGTGGCTGGTTACATCC 
                 AGAGGCTGGTCATAGGGTAA 
                  79 
               
               
                   
               
               
                 CRP 
                  80 
                 GTCTTGACCAGCCTCTCTCA 
                 ACGGTGCTTTGAGGGATACA 
                  81 
               
               
                   
               
               
                 CSH1 
                  82 
                 ACAAGAGACCGGCTCTAGGA 
                 TTGCCACTAGGTGAGCTGTC 
                  83 
               
               
                   
               
               
                 CSH2 
                  84 
                 CGTTCCGTTATCCAGGCTTTT 
                 ACTCCTGGTAGGTGTCAATGG 
                  85 
               
               
                   
               
               
                 CSHL1 
                  86 
                 TTAGAGCTGCTCCACATCTCC 
                 ACCAGGTTGTTGGTGAAGGTA 
                  87 
               
               
                   
               
               
                 CUX2 
                  88 
                 TCCATCACCAAGAGGGTGAA 
                 CAGGATGCTTTCCCCAAACA 
                  89 
               
               
                   
               
               
                 CYP3A7 
                  90 
                 ACGTGCATTGTGCTCTCTCA 
                 CAGCACTGATTTGGTCATCTCC 
                  91 
               
               
                   
               
               
                 DAPP1 
                  92 
                 TGGGCACCAAAGAAGGTTA 
                 TTCCTGTGCAGAGTAAACCA 
                  93 
               
               
                   
               
               
                 DCX 
                  94 
                 ATCTCTACGCCCACCAGTCC 
                 AGCGAGTCCGAGTCATCCAA 
                  95 
               
               
                   
               
               
                 DEFA3 
                  96 
                 GACGAAAGCTTGGCTCCAAA 
                 GTTCCATAGCGACGTTCTCC 
                  97 
               
               
                   
               
               
                 DEFA4 
                  98 
                 TGGGATAAAAGCTCTGCTCTTCA 
                 TGTTCGCCGGCAGAATACTA 
                  99 
               
               
                   
               
               
                 DGCR14 
                 100 
                 ACAAGGCCAAGAATTCCCTCA 
                 TGCCGGGGCTTCTTAAACA 
                 101 
               
               
                   
               
               
                 DLX2 
                 102 
                 TTCGTCCCCAGCCAACAA 
                 TGGCTTCCCGTTCACTATCC 
                 103 
               
               
                   
               
               
                 EGFR 
                 104 
                 GCAGTGACTTTCTCAGCAACA 
                 TTGGGACAGCTTGGATCACA 
                 105 
               
               
                   
               
               
                 ELANE 
                 106 
                 CTCTGCCGTCGCAGCAA 
                 TGGATTAGCCCGTTGCAGAC 
                 107 
               
               
                   
               
               
                 ENAH 
                 108 
                 GCCGGAGCAAAACTTAGGAAA 
                 AGGCGGAGTTCACACCAATA 
                 109 
               
               
                   
               
               
                 EPB42 
                 110 
                 GCCAAGCTCTGGAGGAAGAA 
                 GAGAAGAACAGGCCGATGGTTA 
                 111 
               
               
                   
               
               
                 EPOR 
                 112 
                 ATCCTGGTGCTGCTGAC 
                 GGCCAGATCTTCTGCTTCA 
                 113 
               
               
                   
               
               
                 EPX 
                 114 
                 AGTTCAGAAGAGCCCGAGAC 
                 GCGCTGTCTTTTGGTGAAAAC 
                 115 
               
               
                   
               
               
                 EVX1 
                 116 
                 TACCGGGAGAACTACGTATCCA 
                 ATGCGCCGGTTCTGGAA 
                 117 
               
               
                   
               
               
                 FABP1 
                 118 
                 AGGAATGTGAGCTGGAGACA 
                 TTGTCACCTTCCAACTGAACC 
                 119 
               
               
                   
               
               
                 FABP7 
                 120 
                 GCTACCTGGAAGCTGACCAA 
                 CCACCTGCCTAGTGGCAAA 
                 121 
               
               
                   
               
               
                 FAM212B-AS1 
                 122 
                 GGAAAGGGGTGGATGTGTCA 
                 CACCCAGGATGTCCTTGTTCTA 
                 123 
               
               
                   
               
               
                 FGA 
                 124 
                 ATGTTAGAGCTCAGTTGGTTGATA 
                 TACTGCATGACCCTCGACAA 
                 125 
               
               
                   
               
               
                 FGB 
                 126 
                 ATATTGTCGCACCCCATGCA 
                 ACCTCCTTTCCTGATAATTTCCTCAC 
                 127 
               
               
                   
               
               
                 FOXG1 
                 128 
                 GCCAGCAGCACTTTGAGTTA 
                 TGAGTCAACACGGAGCTGTA 
                 129 
               
               
                   
               
               
                 FRMD4B 
                 130 
                 GAAACCCAGCCAGAAAGCAA 
                 AGGTGGTGGTGTCAGACAAA 
                 131 
               
               
                   
               
               
                 FRZB 
                 132 
                 CCTCTGCCCTCCACTTAATGTTA 
                 CAGCTATAGAGCCTTCCACCAA 
                 133 
               
               
                   
               
               
                 FSTL3 
                 134 
                 CCGGACCTGAGCGTCATGTA 
                 GCACACCACGTGCTCACA 
                 135 
               
               
                   
               
               
                 GAPDH 
                 136 
                 GAACGGGAAGCTTGTCATCAA 
                 ATCGCCCCACTTGATTTTGG 
                 137 
               
               
                   
               
               
                 GCA 
                 138 
                 TCAGTTTGGAAACCTGCAGAA 
                 GCTGCCCATAGCTCTTTGAA 
                 139 
               
               
                   
               
               
                 GH2 
                 140 
                 CCCGTCGCCTGTACCA 
                 TGTTGGAATAGACTCTGAGAAGCA 
                 141 
               
               
                   
               
               
                 GNAZ 
                 142 
                 CGGCTACGACCTGAAACTCTA 
                 TGAGTGAGGTGTTGATGAACCA 
                 143 
               
               
                   
               
               
                 GPR116 
                 144 
                 CCAGAGGCAGTGCAAACATAA 
                 AGAAATTGGGTCCGGGGTTA 
                 145 
               
               
                   
               
               
                 GRHL2 
                 146 
                 ACTCCGGACAGCACATACA 
                 CCAACTGAAGCACTCCGAAA 
                 147 
               
               
                   
               
               
                 GSN 
                 148 
                 AAGACCTGGCAACGGATGAC 
                 TTGAGAATCCTTTCCAACCCAGAC 
                 149 
               
               
                   
               
               
                 GYPB 
                 150 
                 ACAACTTGTCCATCGTTTCAC 
                 ACCAGCCATCACACACAA 
                 151 
               
               
                   
               
               
                 HAL 
                 152 
                 AGAACTGAACAGCGCAACA 
                 GCTGGGTATTCACCATGGAA 
                 153 
               
               
                   
               
               
                 HBG2 
                 154 
                 GGTGACCGTTTTGGCAATCC 
                 CACTGGCCACTCCAGTCAC 
                 155 
               
               
                   
               
               
                 HIST1H2BM 
                 156 
                 GCCTGGCGCATTACAACAA 
                 CAATTCCCCGGGTAGCAGTA 
                 157 
               
               
                   
               
               
                 HMGB3 
                 158 
                 CGGCAAAGCTGAAGGAGAAGTA 
                 CAGGACCCTTTGCACCATCA 
                 159 
               
               
                   
               
               
                 HMGN2 
                 160 
                 ACACAGTGCTAGGTGCAGTTA 
                 TCCATACTCCCAGCCTTTCAC 
                 161 
               
               
                   
               
               
                 HS6ST1 
                 162 
                 AAGTTCATCCGGCCCTTCA 
                 GGTGTCTTCATCCACCTCCA 
                 163 
               
               
                   
               
               
                 HSD17B1 
                 164 
                 TGGACGTAAGGGACTCAAAATCC 
                 CCCAGGCCTGCGTTACA 
                 165 
               
               
                   
               
               
                 HSD3B1 
                 166 
                 TGTGCCTTACGACCCATGTA 
                 GTTGTTCAGGGCCTCGTTTA 
                 167 
               
               
                   
               
               
                 HSPB8 
                 168 
                 GCAAGAAGGTGGCATTGTTTCTA 
                 TCTGGGGAAAGTGAGGCAAA 
                 169 
               
               
                   
               
               
                 ITIH2 
                 170 
                 AGAGAAGAGAAGGCTGGTGAAC 
                 TCCAGGTTGTCAGGAGCAAA 
                 171 
               
               
                   
               
               
                 KLF9 
                 172 
                 TCCCATCTCAAAGCCCATTACA 
                 CTCGTCTGAGCGGGAGAA 
                 173 
               
               
                   
               
               
                 KNG1 
                 174 
                 CTGGCAGGACTGTGAGTACAA 
                 ATTTCGTACTGCTCCTCTTCCC 
                 175 
               
               
                   
               
               
                 KRT8 
                 176 
                 TGACCGACGAGATCAACTTCC 
                 TGTGCCTTGACCTCAGCAA 
                 177 
               
               
                   
               
               
                 KRT81 
                 178 
                 TGAAGGCATTGGGGCTGTG 
                 AGCCTGACACGCAGAGGT 
                 179 
               
               
                   
               
               
                 LGALS14 
                 180 
                 TGTGCATCTATGTGCGTCAC 
                 GGAATCGATGGGCAAAGTTGTA 
                 181 
               
               
                   
               
               
                 LHX2 
                 182 
                 CAAAAGACGGGCCTCACCAA 
                 CGTAAGAGGTTGCGCCTGAA 
                 183 
               
               
                   
               
               
                 LIPC 
                 184 
                 CATCGGTGGAACGCACAA 
                 GGGCACTTCCCTCAAACAAA 
                 185 
               
               
                   
               
               
                 LRRN3 
                 186 
                 GCCTTGGTTGGACTGGAAAA 
                 TTTGAAGAGCAACATGGGGTAC 
                 187 
               
               
                   
               
               
                 LTF 
                 188 
                 CTCCCAGGAACCGTACTTCA 
                 CTCTGATAAAAGCCACGTCTCC 
                 189 
               
               
                   
               
               
                 LYPLAL1 
                 190 
                 CATCAAGATGTGGCAGGAGTA 
                 TGCAGTACCATGACACTGAAATA 
                 191 
               
               
                   
               
               
                 MAP3K7CL 
                 192 
                 GACTCCATTCCTTTGGTTTTTTCC 
                 CCATGGATTCCTCGGAGTCA 
                 193 
               
               
                   
               
               
                 MEF2C 
                 194 
                 TGGTCTGATGGGTGGAGACC 
                 TGAGTTTCGGGGATTGCCATAC 
                 195 
               
               
                   
               
               
                 MMD 
                 196 
                 TCTCACAATGGGATTCTCTCCA 
                 CAGGCAAGTTCCTGAAGTCC 
                 197 
               
               
                   
               
               
                 MMP8 
                 198 
                 TGCCGAAGAAACATGGACCAA 
                 AGCCCCAAAGAATGGCCAAA 
                 199 
               
               
                   
               
               
                 MN1 
                 200 
                 AGAAGGCCAAACCCCAGAA 
                 ATGCTGAGGCCTTGTTTGC 
                 201 
               
               
                   
               
               
                 MOB1B 
                 202 
                 GAGAGTTGTCCAGTGATGTCA 
                 GTCCTGAACCCAAGTCATCA 
                 203 
               
               
                   
               
               
                 MPO 
                 204 
                 CATCGGTACCCAGTTCAGGAA 
                 TGCTGCATGCTGAACACAC 
                 205 
               
               
                   
               
               
                 NFATC1 
                 206 
                 TCCTCTCCAACACCAAAGTCC 
                 AGGATTCCGGCACAGTCAA 
                 207 
               
               
                   
               
               
                 NFATC2 
                 208 
                 TGGAAGCCACGGTGGATAA 
                 TGTGCGGATATGCTTGTTCC 
                 209 
               
               
                   
               
               
                 NPY1R 
                 210 
                 TCTGCTCCCTTCCATTCCC 
                 GAATTCTTCATTCCCTTGAACTGAAC 
                 211 
               
               
                   
               
               
                 NTSR1 
                 212 
                 CGCCTCATGTTCTGCTACA 
                 TAGAAGAGTGCGTTGGTCAC 
                 213 
               
               
                   
               
               
                 OAZ1 
                 214 
                 CGAGCCGACCATGTCTTCA 
                 AAGCTGAAGGTTCGGAGCAA 
                 215 
               
               
                   
               
               
                 OTC 
                 216 
                 CCAGGCTTTCCAAGGTTACCA 
                 TGGCTTTCTGGGCAAGCA 
                 217 
               
               
                   
               
               
                 P2RY12 
                 218 
                 ACTGGATACATTCAAACCCTCCA 
                 TGGTGCACAGACTGGTGTTA 
                 219 
               
               
                   
               
               
                 PAPPA 
                 220 
                 GTACTGTGGCGATGGCATTATAC 
                 AGAAAAGGGAGCAGCCATCA 
                 221 
               
               
                   
               
               
                 PAPPA2 
                 222 
                 ACAGTGGAAGCCTGGGTTAA 
                 ACAGTGTGGGAGCAGTTATCA 
                 223 
               
               
                   
               
               
                 PCDH11X 
                 224 
                 CTGGCATCCAGTTGACGAAA 
                 CATCAGGGCCTAGCAGGTAA 
                 225 
               
               
                   
               
               
                 PGLYRP1 
                 226 
                 GTGCAGCACTACCACATGAA 
                 TATACGAGCCCGTCTTCTCC 
                 227 
               
               
                   
               
               
                 PKHD1L1 
                 228 
                 GCCAGCTGCTATATCACACAAA 
                 AAACCCAGGGCTACTTCCAA 
                 229 
               
               
                   
               
               
                 PLAC1 
                 230 
                 GCCACATTTCAAAGGAAACTGAC 
                 TCCCTGCAGCCAATCAGATA 
                 231 
               
               
                   
               
               
                 PLAC4 
                 232 
                 CCACCAAGAAGCCACTTTCC 
                 TACCAGCAATGCCAGGGTTA 
                 233 
               
               
                   
               
               
                 POLE2 
                 234 
                 AGAAACTGCGTCCGTTTTCC 
                 GGAGTCAGATGTCCTTGGGATAA 
                 235 
               
               
                   
               
               
                 POU3F2 
                 236 
                 CGGATCAAACTGGGATTTACCC 
                 CGAGAACACGTTGCCATACA 
                 237 
               
               
                   
               
               
                 PPBP 
                 238 
                 TCTGGCTTCCTCCACCAAA 
                 CAGCGGAGTTCAGCATACAA 
                 239 
               
               
                   
               
               
                 PRDX5 
                 240 
                 GTTCGGCTCCTGGCTGAT 
                 CAAAGATGGACACCAGCGAATC 
                 241 
               
               
                   
               
               
                 PRG2 
                 242 
                 GGGGCAGTTTCTGCTCTTCA 
                 TCATCCTCAGGCAGCGTCTTA 
                 243 
               
               
                   
               
               
                 PSG1 
                 244 
                 GCAGGATCCTACACCTTACACA 
                 TGCTGGAGATGGAGGGCTTA 
                 245 
               
               
                   
               
               
                 PSG2 
                 246 
                 CTGGCGAGGAAAGCTCCA 
                 CAGAAATGACATCACAGCTGCTA 
                 247 
               
               
                   
               
               
                 PSG4 
                 248 
                 CTCCCCAGCATTTACCCTTCA 
                 GGTTAGACTCGGCGAAGCA 
                 249 
               
               
                   
               
               
                 PSG7 
                 250 
                 ACCCAGTCACCCTGAATGTC 
                 GCAGGACAAGTAGAGGTTTTGTC 
                 251 
               
               
                   
               
               
                 PTGER3 
                 252 
                 GTCGGTCTGCTGGTCTCC 
                 TGTGTCTTGCAGTGCTCAAC 
                 253 
               
               
                   
               
               
                 RAB11A 
                 254 
                 AGGCACAGATATGGGACACA 
                 ATAAGGCACCTACAGCTCCA 
                 255 
               
               
                   
               
               
                 RAB27B 
                 256 
                 ACCAGATCAGAGGGAAGTCA 
                 CAGTTGCTGCACTTGTTTCA 
                 257 
               
               
                   
               
               
                 RAP1GAP 
                 258 
                 GGAAGCAGGATGGATGAACA 
                 CTCGGGTATGGAATGTAGTCC 
                 259 
               
               
                   
               
               
                 RGS18 
                 260 
                 TGAAGACACCCGCTCCAGTA 
                 CCCCATTTCACTGCCTCTTCA 
                 261 
               
               
                   
               
               
                 RHCE 
                 262 
                 TGGGAAGGTGGTCATCACAC 
                 CAGCACCCGCTGAGATCA 
                 263 
               
               
                   
               
               
                 RNASE2 
                 264 
                 GCCAAGATCCCATCTCTCCA 
                 AGGCACTTCAGCTCAGGAAA 
                 265 
               
               
                   
               
               
                 RPL23AP7 
                 266 
                 CTGGCTGTGGGTGTGGTACT 
                 CGCTCCACTCCCTCTAGGC 
                 267 
               
               
                   
               
               
                 S100A8 
                 268 
                 GCTAGAGACCGAGTGTCCTCA 
                 CCAGAATGAGGAACTCCTGGAA 
                 269 
               
               
                   
               
               
                 S100A9 
                 270 
                 TCAAAGAGCTGGTGCGAAAA 
                 ATTTGTGTCCAGGTCCTCCA 
                 271 
               
               
                   
               
               
                 S100P 
                 272 
                 GAAGGAGCTACCAGGCTTCC 
                 AGCAATTTATCCACGGCATCC 
                 273 
               
               
                   
               
               
                 SAMD9 
                 274 
                 CTTCGAGAAGTCTTGCAACC 
                 GCCAGAATAAGAGGGAAGCTA 
                 275 
               
               
                   
               
               
                 SATB2 
                 276 
                 TTTGCCAAAGTGGCTGCAAA 
                 TTTCTGGGCTTGGGTTCTCC 
                 277 
               
               
                   
               
               
                 SEMA3B 
                 278 
                 TGCACCAGTGGGTGTCATA 
                 GTGGAACTGAAGGTGCCAAA 
                 279 
               
               
                   
               
               
                 SERPINA7 
                 280 
                 AGAAGTGGAACCGCTTACTACA 
                 AGTGTGGCTCCAAGGTCATA 
                 281 
               
               
                   
               
               
                 SLC12A8 
                 282 
                 GCTGCCATCGTGTATTTCTACA 
                 AGACCTCATCCACCGGAAAA 
                 283 
               
               
                   
               
               
                 SLC2A2 
                 284 
                 GGGAGCACTTGGCACTTTTCA 
                 GCAGGATGTGCCACAGATCA 
                 285 
               
               
                   
               
               
                 SLC38A4 
                 286 
                 GGTCCTTCCCATCTACAGTGAA 
                 AGCATCCCCGTGATGGAAATA 
                 287 
               
               
                   
               
               
                 SLC4A1 
                 288 
                 TGCTGCCGCTCATCTTCA 
                 CAAAGGTTGCCTTGGCATCA 
                 289 
               
               
                   
               
               
                 SLITRK3 
                 290 
                 GACCTGGCGCTCCAGTTTA 
                 CCTCTGTGAAGCATCTCAGCTA 
                 291 
               
               
                   
               
               
                 TBC1D15 
                 292 
                 AAGACGGCTTGATTTCAGGAA 
                 GCATCATCCAATGGTCTCCA 
                 293 
               
               
                   
               
               
                 TFIP11 
                 294 
                 TGTTAAGCAGGACGACTTTCC 
                 CCTTTCTGGCTGGGCTTAAA 
                 295 
               
               
                   
               
               
                 VCAN 
                 296 
                 GGTGCCTCTGCCTTCCAA 
                 TTGTGCCAGCCATAGTCACA 
                 297 
               
               
                   
               
               
                 VGLL1 
                 298 
                 AGAGTGAAGGTGTGATGCTGAA 
                 GCACGGTTTGTGACAGGTAC 
                 299 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Key: “Forward” Forward primer comprises sequence corresponding to bases a-b of SEQ ID NO: X. E.g., Forward 
               
               
                 primer comprises bases 30-45 of SEQ ID NO: 1. “Reverse” Reverse primer comprises reverse complement of sequence 
               
               
                 corresponding to bases c-d of SEQ ID NO: X.E.g., Reverse primer comprises reverse complement of bases 500-520 of SEQ ID NO: 1. 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 Exemplary 
                 Exemplary 
                 Exemplary 
               
               
                   
                 SEQ ID 
                 Primer Pair A 
                 Primer Pair B 
                 Primer Pair C 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Gene 
                 NO: X 
                 FORWARD 
                 REVERSE 
                 FORWARD 
                 REVERSE 
                 FORWARD 
                 REVERSE 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 CGA mRNA transcript 861 bp 
                 1 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 CAPN6 mRNA transcript 3604 bp 
                 2 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 CGB mRNA transcript 933 bp 
                 3 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 ALPP mRNA transcript 2883 bp 
                 4 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 CSHL1 mRNA transcript 661 bp 
                 5 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 PLAC4 mRNA transcript 10009 bp 
                 6 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 PSG7 mRNA transcript 2046 bp 
                 7 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 PAPPA mRNA transcript 11025 bp 
                 8 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 LGALS14 mRNA transcript 794 bp 
                 9 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 CLCN3 mRNA transcript 6299 bp 
                 10 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 DAPP1 mRNA transcript 3006 bp 
                 11 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 POLE2 mRNA transcript 1861 bp 
                 12 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 PPBP mRNA transcript 1307 bp 
                 13 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 LYPLAL1 mRNA transcript 1922 bp 
                 14 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 MAP3K7CL mRNA transcript 2269 bp 
                 15 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 MOB1B mRNA transcript 7091 bp 
                 16 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 RAB27B mRNA transcript 7003 bp 
                 17 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 RGS18 mRNA transcript 2158 bp 
                 18 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                 TBC1D15 mRNA transcript 5852 bp 
                 19 
                 30-45 
                 500-520 
                 45-60 
                 400-420 
                 100-120 
                 600-620 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Key: Probe comprises sequence corresponding to bases a-b of  
               
               
                 SEQ ID NO: X. or the complement thereof 
               
            
           
           
               
               
               
               
               
            
               
                   
                 SEQ ID 
                 Exemplary 
                 Exemplary 
                 Exemplary 
               
               
                 Gene 
                 NO: X 
                 Probe A 
                 Probe B 
                 Probe C 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 CGA mRNA transcript 861 bp 
                 1 
                 100-140 
                 200-240 
                 300-340 
               
               
                 CAPN6 mRNA transcript 3604 bp 
                 2 
                 100-140 
                 200-240 
                 300-340 
               
               
                 CGB mRNA transcript 933 bp 
                 3 
                 100-140 
                 200-240 
                 300-340 
               
               
                 ALPP mRNA transcript 2883 bp 
                 4 
                 100-140 
                 200-240 
                 300-340 
               
               
                 CSHL1 mRNA transcript 661 bp 
                 5 
                 100-140 
                 200-240 
                 300-340 
               
               
                 PLAC4 mRNA transcript 10009 bp 
                 6 
                 100-140 
                 200-240 
                 300-340 
               
               
                 PSG7 mRNA transcript 2046 bp 
                 7 
                 100-140 
                 200-240 
                 300-340 
               
               
                 PAPPA mRNA transcript 11025 bp 
                 8 
                 100-140 
                 200-240 
                 300-340 
               
               
                 LGALS14 mRNA transcript 794 bp 
                 9 
                 100-140 
                 200-240 
                 300-340 
               
               
                 CLCN3 mRNA transcript 6299 bp 
                 10 
                 100-140 
                 200-240 
                 300-340 
               
               
                 DAPP1 mRNA transcript 3006 bp 
                 11 
                 100-140 
                 200-240 
                 300-340 
               
               
                 POLE2 mRNA transcript 1861 bp 
                 12 
                 100-140 
                 200-240 
                 300-340 
               
               
                 PPBP mRNA transcript 1307 bp 
                 13 
                 100-140 
                 200-240 
                 300-340 
               
               
                 LYPLAL1 mRNA transcript 1922 bp 
                 14 
                 100-140 
                 200-240 
                 300-340 
               
               
                 MAP3K7CL mRNA transcript 2269 bp 
                 15 
                 100-140 
                 200-240 
                 300-340 
               
               
                 MOB1B mRNA transcript 7091 bp 
                 16 
                 100-140 
                 200-240 
                 300-340 
               
               
                 RAB27B mRNA transcript 7003 bp 
                 17 
                 100-140 
                 200-240 
                 300-340 
               
               
                 RGS18 mRNA transcript 2158 bp 
                 18 
                 100-140 
                 200-240 
                 300-340 
               
               
                 TBC1D15 mRNA transcript 5852 bp 
                 19 
                 100-140 
                 200-240 
                 300-340 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 LIST OF EXEMPLARY mRNA TRANSCRIPTS: 
               
            
           
           
               
               
               
            
               
                 SEQ ID 
                   
                   
               
               
                 NO: 
                 Specification Identity 
                 Accession No. 
               
               
                   
               
               
                  1 
                 CGA mRNA transcript 861 bp 
                 NM_001252383.1 
               
               
                  2 
                 CAPN6 mRNA transcript 3604 bp 
                 NM_014289.3 
               
               
                  3 
                 CGB mRNA transcript 933 bp 
                 NM_000737.3 
               
               
                  4 
                 ALPP mRNA transcript 2883 bp 
                 NM_001632.3 
               
               
                  5 
                 CSHL1 mRNA transcript 661 bp 
                 NM_001318.2 
               
               
                  6 
                 PLAC4 mRNA transcript 10009 bp 
                 NM_182832.2 
               
               
                  7 
                 PSG7 mRNA transcript 2046 bp 
                 NM_002783.2 
               
               
                  8 
                 PAPPA mRNA transcript 11025 bp 
                 NM_002581.3 
               
               
                  9 
                 LGALS14 mRNA transcript 794 bp 
                 NM_020129.2 
               
               
                 10 
                 CLCN3 mRNA transcript 6299 bp 
                 NM_173872 
               
               
                 11 
                 DAPP1 mRNA transcript 3006 bp 
                 NM_001306151 
               
               
                 12 
                 POLE2 mRNA transcript 1861 bp 
                 NM_002692 
               
               
                 13 
                 PPBP mRNA transcript 1307 bp 
                 NM_002704 
               
               
                 14 
                 LYPLAL1 mRNA transcript 1922 bp 
                 NM_138794 
               
               
                 15 
                 MAP3K7CL mRNA transcript 2269 bp 
                 NM_001286617 
               
               
                 16 
                 MOB1B mRNA transcript 7091 bp 
                 NM_001244766 
               
               
                 17 
                 RAB27B mRNA transcript 7003 bp 
                 NM_004163 
               
               
                 18 
                 RGS18 mRNA transcript 2158 bp 
                 NM_130782 
               
               
                 19 
                 TBC1D15 mRNA transcript 5852 bp 
                 NM_001146214 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
               
                   
               
               
                 SEQUENCES OF EXEMPLARY mRNA TRANSCRIPTS: 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 CGA mRNA transcript 861 bp 
               
               
                 SEQ ID NO: 1 
               
            
           
           
               
               
            
               
                     1 
                 acactctgct ggtataaaag caggtgagga cttcattaac tgcagttact gagaactcat 
               
               
                   
               
               
                    61 
                 aagacgaagc taaaatccct cttcggatcc acagtcaacc gccctgaaca catcctgcaa 
               
               
                   
               
               
                   121 
                 aaagcccaga gaaaggagcg ccatggatta ctacagaaaa tatgcagcta tctttctggt 
               
               
                   
               
               
                   181 
                 cacattgtcg gtgtttctgc atgttctcca ttccgctcct gatgtgcagg agacagggtt 
               
               
                   
               
               
                   241 
                 tcaccatgtt gcccaggctg ctctcaaact cctgagctca agcaatccac ccactaaggc 
               
               
                   
               
               
                   301 
                 ctcccaaagt gctaggatta cagattgccc agaatgcacg ctacaggaaa acccattctt 
               
               
                   
               
               
                   361 
                 ctcccagccg ggtgccccaa tacttcagtg catgggctgc tgcttctcta gagcatatcc 
               
               
                   
               
               
                   421 
                 cactccacta aggtccaaga agacgatgtt ggtccaaaag aacgtcacct cagagtccac 
               
               
                   
               
               
                   481 
                 ttgctgtgta gctaaatcat ataacagggt cacagtaatg gggggtttca aagtggagaa 
               
               
                   
               
               
                   541 
                 ccacacggcg tgccactgca gtacttgtta ttatcacaaa tcttaaatgt tttaccaagt 
               
               
                   
               
               
                   601 
                 gctgtcttga tgactgctga ttttctggaa tggaaaatta agttgtttag tgtttatggc 
               
               
                   
               
               
                   661 
                 tttgtgagat aaaactctcc ttttccttac cataccactt tgacacgctt caaggatata 
               
               
                   
               
               
                   721 
                 ctgcagcttt actgccttcc tccttatcct acagtacaat cagcagtcta gttcttttca 
               
               
                   
               
               
                   781 
                 tttggaatga atacagcatt tagcttgttc cactgcaaat aaagcctttt aaatcatcat 
               
               
                   
               
               
                   841 
                 tcaaaaaaaa aaaaaaaaaa a 
               
               
                   
               
            
           
           
               
            
               
                 CAPN6 mRNA transcript 3604 bp 
               
               
                 SEQ ID NO: 2 
               
            
           
           
               
               
            
               
                     1 
                 gagcagagct tggtacagcc caaatagttt tcaggttaag aaagccagaa tctttgttca 
               
               
                   
               
               
                    61 
                 gccacactga ctgaacagac ttttagtggg gttacctggc taacagcagc agcggcaacg 
               
               
                   
               
               
                   121 
                 gcagcagcag cagcagcagc agcagcagca gcagcagggc tcctgggata actcaggcat 
               
               
                   
               
               
                   181 
                 agttcaacac tatgggtcct cctctgaagc tcttcaaaaa ccagaaatac caggaactga 
               
               
                   
               
               
                   241 
                 agcaggaatg catcaaagac agcagacttt tctgtgatcc aacatttctg cctgagaatg 
               
               
                   
               
               
                   301 
                 attctctttt ctacaaccga ctgcttcctg gaaaggtggt gtggaaacgt ccccaggaca 
               
               
                   
               
               
                   361 
                 tctgtgatga cccccatctg attgtgggca acattagcaa ccaccagctg acccaaggga 
               
               
                   
               
               
                   421 
                 gactggggca caagccaatg gtttctgcat tttcctgttt ggctgttcag gagtctcatt 
               
               
                   
               
               
                   481 
                 ggacaaagac aattcccaac cataaggaac aggaatggga ccctcaaaaa acagaaaaat 
               
               
                   
               
               
                   541 
                 acgctgggat atttcacttt cgtttctggc attttggaga atggactgaa gtggtgattg 
               
               
                   
               
               
                   601 
                 atgacttgtt gcccaccatt aacggagatc tggtcttctc tttctccact tccatgaatg 
               
               
                   
               
               
                   661 
                 agttttggaa tgctctgctg gaaaaagctt atgcaaagct gctaggctgt tatgaggccc 
               
               
                   
               
               
                   721 
                 tggatggttt gaccatcact gatattattg tggacttcac gggcacattg gctgaaactg 
               
               
                   
               
               
                   781 
                 ttgacatgca gaaaggaaga tacactgagc ttgttgagga gaagtacaag ctattcggag 
               
               
                   
               
               
                   841 
                 aactgtacaa aacatttacc aaaggtggtc tgatctgctg ttccattgag tctcccaatc 
               
               
                   
               
               
                   901 
                 aggaggagca agaagttgaa actgattggg gtctgctgaa gggccatacc tataccatga 
               
               
                   
               
               
                   961 
                 ctgatattcg caaaattcgt cttggagaga gacttgtgga agtcttcagt gctgagaagg 
               
               
                   
               
               
                  1021 
                 tgtatatggt tcgcctgaga aaccccttgg gaagacagga atggagtggc ccctggagtg 
               
               
                   
               
               
                  1081 
                 aaatttctga agagtggcag caactgactg catcagatcg caagaacctg gggcttgtta 
               
               
                   
               
               
                  1141 
                 tgtctgatga tggagagttt tggatgagct tggaggactt ttgccgcaac tttcacaaac 
               
               
                   
               
               
                  1201 
                 tgaatgtctg ccgcaatgtg aacaacccta tttttggccg aaaggagctg gaatcggtgt 
               
               
                   
               
               
                  1261 
                 tgggatgctg gactgtggat gatgatcccc tgatgaaccg ctcaggaggc tgctataaca 
               
               
                   
               
               
                  1321 
                 accgtgatac cttcctgcag aatccccagt acatcttcac tgtgcctgag gatgggcaca 
               
               
                   
               
               
                  1381 
                 aggtcattat gtcactgcag cagaaggacc tgcgcactta ccgccgaatg ggaagacctg 
               
               
                   
               
               
                  1441 
                 acaattacat cattggcttt gagctcttca aggtggagat gaaccgcaaa ttccgcctcc 
               
               
                   
               
               
                  1501 
                 accacctcta catccaggag cgtgctggga cttccaccta tattgacacc cgcacagtgt 
               
               
                   
               
               
                  1561 
                 ttctgagcaa gtacctgaag aagggcaact atgtgcttgt cccaaccatg ttccagcatg 
               
               
                   
               
               
                  1621 
                 gtcgcaccag cgagtttctc ctgagaatct tctctgaagt gcctgtccag ctcagggaac 
               
               
                   
               
               
                  1681 
                 tgactctgga catgcccaaa atgtcctgct ggaacctggc tcgtggctac ccgaaagtag 
               
               
                   
               
               
                  1741 
                 ttactcagat cactgttcac agtgctgagg acctggagaa gaagtatgcc aatgaaactg 
               
               
                   
               
               
                  1801 
                 taaacccata tttggtcatc aaatgtggaa aggaggaagt ccgttctcct gtccagaaga 
               
               
                   
               
               
                  1861 
                 atacagttca tgccattttt gacacccagg ccattttcta cagaaggacc actgacattc 
               
               
                   
               
               
                  1921 
                 ctattatagt acaggtctgg aacagccgaa aattctgtga tcagttcttg gggcaggtta 
               
               
                   
               
               
                  1981 
                 ctctggatgc tgaccccagc gactgccgtg atctgaagtc tctgtacctg cgtaagaagg 
               
               
                   
               
               
                  2041 
                 gtggtccaac tgccaaagtc aagcaaggcc acatcagctt caaggttatt tccagcgatg 
               
               
                   
               
               
                  2101 
                 atctcactga gctctaaatc tgcaatccca gagaatcctg acaaagcgtg ccaccctttt 
               
               
                   
               
               
                  2161 
                 attttccgtc aggtgccagg tcttagttaa gattcacaat ctttagaaag aatgagattc 
               
               
                   
               
               
                  2221 
                 acaataatta actcttcctc tcttctgata aattccccat acctcccaat ccaagtagca 
               
               
                   
               
               
                  2281 
                 tctgtagcta cataacctat atacctccag cagctggaca tggggaggcg acagtcctat 
               
               
                   
               
               
                  2341 
                 ctagacatca tacacatttg ccaagaaagg atctctgggg cttccggggg tgagattcaa 
               
               
                   
               
               
                  2401 
                 gcaggacaat aacaagaggc tggacaccct acagatgtct ttgatgtttt cagttgtttg 
               
               
                   
               
               
                  2461 
                 atatatctcc cctgtagggc atgttgagga aggaggaggg ctgatcaagg ccaagctggt 
               
               
                   
               
               
                  2521 
                 ctagcctgac atcctagctc ctgactgaac actatagact tcccagcagc atttcaccca 
               
               
                   
               
               
                  2581 
                 gcagccagag ccggctttaa gtccccaacc cttacagaca ccactgccac caccaccaac 
               
               
                   
               
               
                  2641 
                 cacgaccacc accaccacca ccactcacca ccatcatcac ctccggaaag tgtagtcctg 
               
               
                   
               
               
                  2701 
                 ccctaaccca agtcaccccc gacagtaaat tttaccttca tgttgagaaa gcttcctggt 
               
               
                   
               
               
                  2761 
                 gcttaatcaa gagctggagt tcaatgagtc ctagacagtg agaggggcct gagcttcagc 
               
               
                   
               
               
                  2821 
                 tcaatggaag cctgctgtgt gccacaagac ggaaaagtgg aagaagctgc agtgggagac 
               
               
                   
               
               
                  2881 
                 aaagcctcgg tcccccaccc atccacacac acctacactc acacacgcgc acatgggcgc 
               
               
                   
               
               
                  2941 
                 gcacgaacta ccattcaggc agtcagtggg caagaggaaa gataagtaag taccatacac 
               
               
                   
               
               
                  3001 
                 acctaaaaga tgagagaatt catccagaca tattacagcc agtttggggc ccctgactgc 
               
               
                   
               
               
                  3061 
                 aatgtgaaac ctctcgctgc tgctaggttt acaaacaagc ccattgtcct gtgcctccta 
               
               
                   
               
               
                  3121 
                 atatcatttg tactgaagac cccatctggg gacttgagac tttggtccca gcccagactc 
               
               
                   
               
               
                  3181 
                 ctcagacttt tctctcagtt gggatgcttc actcgctggg ggtgtttgtt tgccctctca 
               
               
                   
               
               
                  3241 
                 tttttcagta cttctacaga attttctcta gagtcagtca ttatgaaatg tacttccctc 
               
               
                   
               
               
                  3301 
                 catcttaacc tatcaacttt ctgcccctcc ttcaaggccc agtataaatg ccacctcctc 
               
               
                   
               
               
                  3361 
                 catgaagcct tccctaattc caccccaaac ccccaccttc aacaatattt caacgcttct 
               
               
                   
               
               
                  3421 
                 gcaatgatga aaaagaaaca tagttgtagt acttagccta cctagaccag caagcattca 
               
               
                   
               
               
                  3481 
                 tttttagctc gctcattttt taccatgttt tccagtctgt ttaacttctg cagtgccttc 
               
               
                   
               
               
                  3541 
                 actacactgc cttacataaa ccaaatcaca ataaagttca tattcagtac attgaaaaaa 
               
               
                   
               
               
                  3601 
                 aaaa 
               
               
                   
               
            
           
           
               
            
               
                 CGB mRNA transcript 933 bp 
               
               
                 SEQ ID NO: 3 
               
            
           
           
               
               
            
               
                     1 
                 tgcaggaaag cctcaagtag aggagggttg aggcttcagt ccagcacctt tctcgggtca 
               
               
                   
               
               
                    61 
                 cggcctcctc ctggctccca ggaccccacc ataggcagag gcaggccttc ctacacccta 
               
               
                   
               
               
                   121 
                 ctccctgtgc ctccagcctc gactagtccc tagcactcga cgactgagtc tctgaggtca 
               
               
                   
               
               
                   181 
                 cttcaccgtg gtctccgcct cacccttggc gctggaccag tgagaggaga gggctggggc 
               
               
                   
               
               
                   241 
                 gctccgctga gccactcctg cgcccccctg gccttgtcta cctcttgccc cccgaggggt 
               
               
                   
               
               
                   301 
                 tagtgtcgag ctcaccccag catcctatca cctcctggtg gccttgccgc ccccacaacc 
               
               
                   
               
               
                   361 
                 ccgaggtata aagccaggta cacgaggcag gggacgcacc aaggatggag atgttccagg 
               
               
                   
               
               
                   421 
                 ggctgctgct gttgctgctg ctgagcatgg gcgggacatg ggcatccaag gagccgcttc 
               
               
                   
               
               
                   481 
                 ggccacggtg ccgccccatc aatgccaccc tggctgtgga gaaggagggc tgccccgtgt 
               
               
                   
               
               
                   541 
                 gcatcaccgt caacaccacc atctgtgccg gctactgccc caccatgacc cgcgtgctgc 
               
               
                   
               
               
                   601 
                 agggggtcct gccggccctg cctcaggtgg tgtgcaacta ccgcgatgtg cgcttcgagt 
               
               
                   
               
               
                   661 
                 ccatccggct ccctggctgc ccgcgcggcg tgaaccccgt ggtctcctac gccgtggctc 
               
               
                   
               
               
                   721 
                 tcagctgtca atgtgcactc tgccgccgca gcaccactga ctgcgggggt cccaaggacc 
               
               
                   
               
               
                   781 
                 accccttgac ctgtgatgac ccccgcttcc aggactcctc ttcctcaaag gcccctcccc 
               
               
                   
               
               
                   841 
                 ccagccttcc aagcccatcc cgactcccgg ggccctcgga caccccgatc ctcccacaat 
               
               
                   
               
               
                   901 
                 aaaggcttct caatccgcaa aaaaaaaaaa aaa 
               
               
                   
               
            
           
           
               
            
               
                 ALPP mRNA transcript 2883 bp 
               
               
                 SEQ ID NO: 4 
               
            
           
           
               
               
            
               
                     1 
                 tcagccagtg tggcttcagg tcaagaggct gggcagggtc aaggtggcaa cgaggggaga 
               
               
                   
               
               
                    61 
                 agccgggaca cagttctccc tgatttaaac ccgggcagcc tggagtgcag ctcatactcc 
               
               
                   
               
               
                   121 
                 atgcccagaa ttcctgcctc gccactgtcc tgctgccctc cagacatgct ggggccctgc 
               
               
                   
               
               
                   181 
                 atgctgctgc tgctgctgct gctgggcctg aggctacagc tctccctggg catcatccca 
               
               
                   
               
               
                   241 
                 gttgaggagg agaacccgga cttctggaac cgcgaggcag ccgaggccct gggtgccgcc 
               
               
                   
               
               
                   301 
                 aagaagctgc agcctgcaca gacagccgcc aagaacctca tcatcttcct gggcgatggg 
               
               
                   
               
               
                   361 
                 atgggggtgt ctacggtgac agctgccagg atcctaaaag ggcagaagaa ggacaaactg 
               
               
                   
               
               
                   421 
                 gggcctgaga tacccctggc catggaccgc ttcccatatg tggctctgtc caagacatac 
               
               
                   
               
               
                   481 
                 aatgtagaca aacatgtgcc agacagtgga gccacagcca cggcctacct gtgcggggtc 
               
               
                   
               
               
                   541 
                 aagggcaact tccagaccat tggcttgagt gcagccgccc gctttaacca gtgcaacacg 
               
               
                   
               
               
                   601 
                 acacgcggca acgaggtcat ctccgtgatg aatcgggcca agaaagcagg gaagtcagtg 
               
               
                   
               
               
                   661 
                 ggagtggtaa ccaccacacg agtgcagcac gcctcgccag ccggcaccta cgcccacacg 
               
               
                   
               
               
                   721 
                 gtgaaccgca actggtactc ggacgccgac gtgcctgcct ccgcccgcca ggaggggtgc 
               
               
                   
               
               
                   781 
                 caggacatcg ctacgcagct catctccaac atggacattg acgtgatcct aggtggaggc 
               
               
                   
               
               
                   841 
                 cgaaagtaca tgtttcgcat gggaacccca gaccctgagt acccagatga ctacagccaa 
               
               
                   
               
               
                   901 
                 ggtgggacca ggctggacgg gaagaatctg gtgcaggaat ggctggcgaa gcgccagggt 
               
               
                   
               
               
                   961 
                 gcccggtatg tgtggaaccg cactgagctc atgcaggctt ccctggaccc gtctgtgacc 
               
               
                   
               
               
                  1021 
                 catctcatgg gtctctttga gcctggagac atgaaatacg agatccaccg agactccaca 
               
               
                   
               
               
                  1081 
                 ctggacccct ccctgatgga gatgacagag gctgccctgc gcctgctgag caggaacccc 
               
               
                   
               
               
                  1141 
                 cgcggcttct tcctcttcgt ggagggtggt cgcatcgacc atggtcatca tgaaagcagg 
               
               
                   
               
               
                  1201 
                 gcttaccggg cactgactga gacgatcatg ttcgacgacg ccattgagag ggcgggccag 
               
               
                   
               
               
                  1261 
                 ctcaccagcg aggaggacac gctgagcctc gtcactgccg accactccca cgtcttctcc 
               
               
                   
               
               
                  1321 
                 ttcggaggct accccctgcg agggagctcc atcttcgggc tggcccctgg caaggcccgg 
               
               
                   
               
               
                  1381 
                 gacaggaagg cctacacggt cctcctatac ggaaacggtc caggctatgt gctcaaggac 
               
               
                   
               
               
                  1441 
                 ggcgcccggc cggatgttac cgagagcgag agcgggagcc ccgagtatcg gcagcagtca 
               
               
                   
               
               
                  1501 
                 gcagtgcccc tggacgaaga gacccacgca ggcgaggacg tggcggtgtt cgcgcgcggc 
               
               
                   
               
               
                  1561 
                 ccgcaggcgc acctggttca cggcgtgcag gagcagacct tcatagcgca cgtcatggcc 
               
               
                   
               
               
                  1621 
                 ttcgccgcct gcctggagcc ctacaccgcc tgcgacctgg cgccccccgc cggcaccacc 
               
               
                   
               
               
                  1681 
                 gacgccgcgc acccggggcg gtccgtggtc cccgcgttgc ttcctctgct ggccgggacc 
               
               
                   
               
               
                  1741 
                 ctgctgctgc tggagacggc cactgctccc tgagtgtccc gtccctgggg ctcctgcttc 
               
               
                   
               
               
                  1801 
                 cccatcccgg agttctcctg ctccccacct cctgtcgtcc tgcctggcct ccagcccgag 
               
               
                   
               
               
                  1861 
                 tcgtcatccc cggagtccct atacagaggt cctgccatgg aaccttcccc tccccgtgcg 
               
               
                   
               
               
                  1921 
                 ctctggggac tgagcccatg acaccaaacc tgccccttgg ctgctctcgg actccctacc 
               
               
                   
               
               
                  1981 
                 ccaaccccag ggactgcagg ttgtgccctg tggctgcctg caccccagga aaggaggggg 
               
               
                   
               
               
                  2041 
                 ctcaggccat ccagccacca cctacagccc agtgggtacc aggcaggctc ccttcctggg 
               
               
                   
               
               
                  2101 
                 gaaaagaagc acccagaccc cgcgccccgc tgatctttgc ttcagtcctt gaatcacctg 
               
               
                   
               
               
                  2161 
                 tgggacttga ggactcggga tcttcaggac gcctggagaa gggtggtttc ctgccaccct 
               
               
                   
               
               
                  2221 
                 gctggccaag gaggctcctg gggtggggat caccaggggg attttgacac agccttcggc 
               
               
                   
               
               
                  2281 
                 tgccccccac taagctaatt ccacacccct gtaccccccc agggggccct ctgcctcatg 
               
               
                   
               
               
                  2341 
                 gcaaaggctt gccccaaatc tcaacttctc agacgttcca tacccccaca tgccaatttc 
               
               
                   
               
               
                  2401 
                 agcacccaac tgagatccga ggagctcctg ggaagccctg ggtgcaggac actggtcgag 
               
               
                   
               
               
                  2461 
                 agccaaaggt ccctccccag acatctggac actgggcata gatttctcaa gaaggaagac 
               
               
                   
               
               
                  2521 
                 tcccctgcct ccccagggcc tctgctctcc tgggagacaa agcaataata aaaggaagtg 
               
               
                   
               
               
                  2581 
                 tttgtaatcc cagcactttg ggaggccgag gtgggcggat cacgaggtca ggagatggag 
               
               
                   
               
               
                  2641 
                 accatcctgg ctaacacggt gaaacccctt atctatgcgc ctgtagtccc agctacccag 
               
               
                   
               
               
                  2701 
                 gaggctgaag caggataatc gcttgaaccc gggcggcgga gattgcagtg agccgaggtc 
               
               
                   
               
               
                  2761 
                 atgccactgc actgcagcct gggcgacaga gcgagattct gcctcaaaaa taaacaaata 
               
               
                   
               
               
                  2821 
                 aattttaaaa ataaataaat aataaaagga agtgttagac aatgtaaaaa aaaaaaaaaa 
               
               
                   
               
               
                  2881 
                 aaa 
               
               
                   
               
            
           
           
               
            
               
                 CSHL1 mRNA transcript 661 bp 
               
               
                 SEQ ID NO: 5 
               
            
           
           
               
               
            
               
                     1 
                 agcatcccaa ggcccgactc cccgcaccac tcagggtcct gtggacagct cacctagcgg 
               
               
                   
               
               
                    61 
                 caatggctgc aggaagaagc ctatatcaca aaggaacaga agtattcatt cctgcatgac 
               
               
                   
               
               
                   121 
                 tcccagacct ccttctgctt ctcagactct attccgacat cctccaacat ggaggaaacg 
               
               
                   
               
               
                   181 
                 cagcagaaat ccaacttaga gctgctccac atctccctgc tgctcatcga gtcgcggctg 
               
               
                   
               
               
                   241 
                 gagcccgtgc ggttcctcag gagtaccttc accaacaacc tggtgtatga cacctcggac 
               
               
                   
               
               
                   301 
                 agcgatgact atcacctcct aaaggaccta gaggaaggca tccaaatgct gatggggagg 
               
               
                   
               
               
                   361 
                 ctggaagacg gcagccacct gactgggcag accctcaagc agacctacag caagtttgac 
               
               
                   
               
               
                   421 
                 acaaactcgc acaaccatga cgcactgctc aagaactacg ggctgctcca ctgcttcagg 
               
               
                   
               
               
                   481 
                 aaggacatgg acaaggtcga gacattcctg cgcatggtgc agtgccgctc tgtggagggc 
               
               
                   
               
               
                   541 
                 agctgtggct tctaggggcc cgcgtggcat cctgtgaccc ctccccagtg cctctcctgg 
               
               
                   
               
               
                   601 
                 ccctgaaggt gccactccag tgcccaccag ccttgtctta ataaaattaa gttgtattgt 
               
               
                   
               
               
                   661 
                 t 
               
               
                   
               
            
           
           
               
            
               
                 PLAC4 mRNA transcript 10009 bp 
               
               
                 SEQ ID NO: 6 
               
            
           
           
               
               
            
               
                     1 
                 cgtagctcat aatccatttt tataacacct tgctatctat atttacacct ttaaagaaca 
               
               
                   
               
               
                    61 
                 cgggaattta agagggaaga gtaactaggc ttttgctaaa cttgggctaa taaaaccctc 
               
               
                   
               
               
                   121 
                 tgtagagaga tccttaatat aggcatgggg acaacaagga gtatcccaag ggactcgccg 
               
               
                   
               
               
                   181 
                 ctagggtgtc ttttaagcta ttggagcaaa ttcaaatttg gcttaaagaa aaagaaactc 
               
               
                   
               
               
                   241 
                 attttgtatt gcaacaccat ttgggttaaa tacaagttag atgacgaata tatctggcct 
               
               
                   
               
               
                   301 
                 aaacatggtt ctatatacta tagtgatatt ttacgattag gcttattttg taaaagagaa 
               
               
                   
               
               
                   361 
                 ggaaaatggg aagagatccc ttatgtacag gcttttatgg ctctatactg gatcacgtta 
               
               
                   
               
               
                   421 
                 cttccaggca ttagaatgcc atgcataagg gatccccacc tagctgctcc ccatagaaag 
               
               
                   
               
               
                   481 
                 ttcataagcc tccccagagt ctcttcagtc ccccagtcct gagtgggggt tctcgccaat 
               
               
                   
               
               
                   541 
                 tccctaatga gattccaccc caatatcatc aggcaccttt cccccttatc caactagccc 
               
               
                   
               
               
                   601 
                 tagcctatac cctctgctgc ccaagaaaat gagcccaacc agtacaccag gagtggggct 
               
               
                   
               
               
                   661 
                 ccatatcagc ccctaaggtc aagcctgtgt ccactgtgga aagtagttga tggaaatgag 
               
               
                   
               
               
                   721 
                 ggaacactca aagagtacat atgccacttt ccatgtctaa ttagacctta taaaaggaaa 
               
               
                   
               
               
                   781 
                 gaattggcca gttttcagat aaaccagaaa agcttataca agagtttgtt acgttgacta 
               
               
                   
               
               
                   841 
                 tgttcttcaa attgccacga tttacaaata ttgtcatccg cttgctgtgc tgtggggaaa 
               
               
                   
               
               
                   901 
                 aaaaagtaga ggaaaaagtg tgtggttaag ccagtcaatt atgacaaggt taaagaagta 
               
               
                   
               
               
                   961 
                 actcggggaa aagatgaaaa tcccgctctg tttcagggtc ttttagttga agcactcagg 
               
               
                   
               
               
                  1021 
                 aaatatacta atgcaggccc agacacccca gaagggcaag ctctcctggg tatacatttt 
               
               
                   
               
               
                  1081 
                 ctcattcaat cttctcctga cattaggagg aatctacaaa aagcagcaat gggaccttca 
               
               
                   
               
               
                  1141 
                 agtcctatga aacgacgctt aaacatagcc tttaaagttt acaacaacag ggacagggca 
               
               
                   
               
               
                  1201 
                 aaagagggga gtaaaaagaa atagccaaaa agtacaattg ttaacagtga ctttaagcct 
               
               
                   
               
               
                  1261 
                 ccttgcccct caggattact catcttgaga aaatgttaca aaattagcat ctgggatgcc 
               
               
                   
               
               
                  1321 
                 tagacaagac ttgatgcctg acttgctgac ccctgggcca gaatcactgc gcctactata 
               
               
                   
               
               
                  1381 
                 cgcaaaaggg cccctggcaa tgcaaatgtc ctaactgctc tggtgagaga gaacaataac 
               
               
                   
               
               
                  1441 
                 aacaaaaagc ttccatcaat actagagcta accttctcct actagcccca gtgagctgct 
               
               
                   
               
               
                  1501 
                 tagctcaagt aagtttactg tcccagagga cagctttcca cagtggcaga taagcagccg 
               
               
                   
               
               
                  1561 
                 cctgaacatt tttctttggt atttccacca ctgagtgtgc tctccagtgg cgtggggact 
               
               
                   
               
               
                  1621 
                 ccagaatctc cttttgagca atgcagtttg cttcctcccc tttttagttg atgctatggg 
               
               
                   
               
               
                  1681 
                 attccctgtc ctgccttttc ctgttttcca tacctatcgg ggcaaacaaa atttggccag 
               
               
                   
               
               
                  1741 
                 gtagatgggt cccagttctg taaataactt gaatccagtt gtcttgtata ggtcatttta 
               
               
                   
               
               
                  1801 
                 tttaatatgt ttttgggtat atgtacatgt attgtgatgt gtgttacatc tagcgtgctg 
               
               
                   
               
               
                  1861 
                 tcaaactggc ttatagataa aagaacactc atacattcaa caaataagac tactgaaagc 
               
               
                   
               
               
                  1921 
                 ttattagttt gaagagaatc ttgtatcttc taaaatttaa ctttaggatt tttacctagg 
               
               
                   
               
               
                  1981 
                 taagtcactg atgttcatag gctttaaaat ggttaaaatg gctttaaatg gtgaccagct 
               
               
                   
               
               
                  2041 
                 ttgcatggta ccttggttct cggtgatcta gataaagtta aaagtgaaat aattaaatac 
               
               
                   
               
               
                  2101 
                 acgtaaatgg gatatgctta atgtgtggtt taaaatcata aaatggtaga atggttctca 
               
               
                   
               
               
                  2161 
                 gttatagaat gacaatgtct agtgtgaagt tcatgacttc ttccttccta ggtttccata 
               
               
                   
               
               
                  2221 
                 aaatgtgcta aagaaatgta ttctttattg agaaaaaatt ttttgtctaa tccggaagtt 
               
               
                   
               
               
                  2281 
                 actaaatggg aggttcaaaa catgagtgaa ccagtgagta gaaaagagag atgtaaagaa 
               
               
                   
               
               
                  2341 
                 tattatgaat agaaaatgta ttttttgttt gttttgcaag gaaggatata aagaaagagt 
               
               
                   
               
               
                  2401 
                 aattttatat gtggaggaat cctgtatagt aaattcccta tcctagagta aaataacttt 
               
               
                   
               
               
                  2461 
                 aagaaagagg tagtatagaa catgtcagga aattcagcta tgttgtagat ggtctgtgta 
               
               
                   
               
               
                  2521 
                 agtcatctgc acagtgcatg agtgtggagg tgggcgggca ctcattggcc cttgaactcc 
               
               
                   
               
               
                  2581 
                 ttttgagcag tatggaagcc aagaactaga agccaggaaa tggggttgta aaactgattt 
               
               
                   
               
               
                  2641 
                 gtctatggat tttatgtgtt gagctgctgt ggtcttggct tgtagtaatt acctatatga 
               
               
                   
               
               
                  2701 
                 accttccccc ctccccttta gaatttagga caggttcaaa aggccctcca atataaaaat 
               
               
                   
               
               
                  2761 
                 aaaatactgt ccttccccac aaaggaaaaa atagctcccc ggttcaacca ggagacttag 
               
               
                   
               
               
                  2821 
                 tcttgctaaa accttaaaga cagggtaaag acagggatac cccaagaatc aattacaatg 
               
               
                   
               
               
                  2881 
                 aaatggaagg ggccttatca ggtattgtta agtaccccca ctgctgttaa acttcaggga 
               
               
                   
               
               
                  2941 
                 acacctactt gggcacacag atccaggact aaacctgttt cttatgagtc acaggcacaa 
               
               
                   
               
               
                  3001 
                 aggaagggca ctacaaccac aaccaatatc agtaaagctt tggaagacct ctgctaccta 
               
               
                   
               
               
                  3061 
                 tttaaaataa tcaacactca gccagaagag gtaatgtaat gctgtagatg ggaataggag 
               
               
                   
               
               
                  3121 
                 cattgatctt gctcttcttc ctgactgtag tacttccttt ctatggcttt aaccagccac 
               
               
                   
               
               
                  3181 
                 ctcctcctgg gaaacatctc ctgtgggctt gttgggtata gaagctactc taagacccaa 
               
               
                   
               
               
                  3241 
                 ccagatacca tgatgccact gttaattctg tttgctcttc taattaacct aagctagtgt 
               
               
                   
               
               
                  3301 
                 gtatgtggac agggagggtg gacaaaattc tacagtaaat atttcaaaaa ttatagcatc 
               
               
                   
               
               
                  3361 
                 atagaatcat ctttatggct gccagatttg tcatcaacac ccccaggata gacagtttca 
               
               
                   
               
               
                  3421 
                 tcttccgacc tatctggaaa atctcaggac catgtcccca gacctcctaa ctaaccatag 
               
               
                   
               
               
                  3481 
                 caccccaaaa tacccaaacc cctattgtga agtggaactc ttccccactt agtggatccc 
               
               
                   
               
               
                  3541 
                 ccctggaccc tgctgtcccc ctgccctgac cactattatc ggaatctggg aagttgggca 
               
               
                   
               
               
                  3601 
                 tctatatctc cagtgcactc ataactctaa catttgcatc cactcttgca ttaatgacac 
               
               
                   
               
               
                  3661 
                 aaaagtggaa gcttccctgc gatgctctgg tccaactcta gttgccaagt ttccaagacc 
               
               
                   
               
               
                  3721 
                 acggggaggt aaatgagatt ccatttgtga gtgaaaagac catatatggt accttctccc 
               
               
                   
               
               
                  3781 
                 ggatgggaac atacaaagga aaaacaactg cctgatctgg gaaggtgaca gtactacctt 
               
               
                   
               
               
                  3841 
                 cttctagaaa acaaagattg ttcaaccacc accatgagaa caggtggaaa atatctctat 
               
               
                   
               
               
                  3901 
                 agacccaacc tggcaatgaa gtataaacat cgcaccccgc agggcttctc ttggtgccct 
               
               
                   
               
               
                  3961 
                 agttgggttc atttttgttt gtgactatga atgggaagaa gtcacaccct gtaaccactc 
               
               
                   
               
               
                  4021 
                 caactcccta aggagtcacc tcttctttaa ggaatagctt tcccttgtat ctaaaaaact 
               
               
                   
               
               
                  4081 
                 tggaactgac atgaatgaac gttggccact cttacccctc caggggtcac aatctataac 
               
               
                   
               
               
                  4141 
                 gcctaggacc caagaatatc agaaataagt aagcaataaa actaattctg gcaggaatca 
               
               
                   
               
               
                  4201 
                 gggtggcaat aggactagca gcaccctggg gtggctttgc ctaccatgag ttaacgctaa 
               
               
                   
               
               
                  4261 
                 agaacttggc tcaaatccta gaatccttag ccaccaacgg agatcaggca ttaaagagaa 
               
               
                   
               
               
                  4321 
                 ttcaagagtt ccccagactc tggaaaatgt agttgttgat aacagactag cattggatta 
               
               
                   
               
               
                  4381 
                 tttactagct gaacaaggtg gggtcttgtg cagttattaa taaaacctgc tgcacatata 
               
               
                   
               
               
                  4441 
                 ttaactctgg acaggttgag gttaacattc aaaagatcta tgagcaagct acctagttac 
               
               
                   
               
               
                  4501 
                 atagatataa ccagggcact gcccccaact atatctggtc aaccatcaaa agtgccttcc 
               
               
                   
               
               
                  4561 
                 caagtctcac ctgtttttca cctcttctag gacctttgac aactgtcttg ttacaaatgt 
               
               
                   
               
               
                  4621 
                 ttggtccttg cttctttaac ctcttagtaa agtttgtgta ttctagatta ccacagttcc 
               
               
                   
               
               
                  4681 
                 agagacaatg ctggcacaag gcttccagcc catcctgtcc actgacacgg agaatgaaat 
               
               
                   
               
               
                  4741 
                 cgtcctgcct ctgggctcct tagatcaggt atccagagat ttttactcct ccagtgccag 
               
               
                   
               
               
                  4801 
                 gcagggccta cgtccataaa ctcagcagga agtagttacg gaaaacagat ctccgccctt 
               
               
                   
               
               
                  4861 
                 ctgcagcccc cttaagatta aggaggagta tctaatctct gaagggggaa tgaggtagga 
               
               
                   
               
               
                  4921 
                 ggtgggactc aactctggaa gtggggctca ggcactcaga ccaaactgag cactagctaa 
               
               
                   
               
               
                  4981 
                 aataggtcca gggcagatgc tagtttccat aggacacacc gacctgtgtc aagtcagttc 
               
               
                   
               
               
                  5041 
                 accatggctc tggcagcacc cagaagttac caccctcacc ctggaaatgt ctgcataaac 
               
               
                   
               
               
                  5101 
                 tgccccttca tttgcatata attaaaagtg gatacaaata ccactgcaga actgcctctg 
               
               
                   
               
               
                  5161 
                 agctgctact gtgggcgcac agcctgtagg gcagccctgc tttgcaagga gcagcgcctc 
               
               
                   
               
               
                  5221 
                 tgctgctgct gtgcacagcc ggccgcttca ataaaagttg ctaacaccac tggcttgccc 
               
               
                   
               
               
                  5281 
                 ttgagttcct tcctgggcaa agctaagaac cctcccgggc tatgcttcaa tcttagggct 
               
               
                   
               
               
                  5341 
                 cgcctgtcct gcatcactgg gatcatctcc cagtaaacta gccacactta catccatgtg 
               
               
                   
               
               
                  5401 
                 tcagggacat ttctggagaa agcagcccag gacactgttg aataaaacac acaatagtct 
               
               
                   
               
               
                  5461 
                 ctgtggtctt ctccacccca ccccacacca ggcaccctca gcttgattct cctttttaat 
               
               
                   
               
               
                  5521 
                 tgcctgtaag cagggaagca caatgttttc acattctttg taaggccttt gttctactaa 
               
               
                   
               
               
                  5581 
                 aatctaacct cagagcacaa ttttaaacta gatgaaagag ttgctgcgcc tgaagcactg 
               
               
                   
               
               
                  5641 
                 caaacacctc ctcaccacac atgtgcactc accctggaca ccctcactca ccctgacacc 
               
               
                   
               
               
                  5701 
                 ctcactcctc accctggaca ccctcactca ccccagacac cgtcactcct caccctggac 
               
               
                   
               
               
                  5761 
                 acctcactct gcaccctgga caccctcact caccctggac acgttcactc accctgacac 
               
               
                   
               
               
                  5821 
                 cctcactcac cctggacacc ctcactcacc ctggataccc tcactcctca ccctggacac 
               
               
                   
               
               
                  5881 
                 cctcactcac cctggatacc ctcactcctc accctggaca ctctcactca ccctgacacc 
               
               
                   
               
               
                  5941 
                 ctcaatcctc accctggact ccctcactcc tcaccctgga ctccctcact cctcaccctg 
               
               
                   
               
               
                  6001 
                 gacaccctca ctcctcatcc tggacaccct cactcaacct ggacaccctc actcctcacc 
               
               
                   
               
               
                  6061 
                 ctgacaccct cactcctcac cctggacacc ctcactcctc accctgacac cctcactcct 
               
               
                   
               
               
                  6121 
                 caccctggca ccctcagtca ccctgacacc ctcactcctc accctgacac cctcaagtct 
               
               
                   
               
               
                  6181 
                 tcacctccct ggctgcagcc tgggacacgc tttccctaac ttctgaaggc tcagtcctcc 
               
               
                   
               
               
                  6241 
                 tcaagccaat ctcatctcaa attgcacctc ctcagagagg tcttccataa ccgcccttat 
               
               
                   
               
               
                  6301 
                 aaagcaggat tctttcacca ataccccttc ccacatggca ctgtctcaca gcactcctct 
               
               
                   
               
               
                  6361 
                 aaaagtctgt ttacttcctt gacaatctgt cttccttata aggggaggtt ctgtaaaagc 
               
               
                   
               
               
                  6421 
                 caagactctc tctgtctagt tgactgttgc ataccagggc ttagaccaag gccctgacat 
               
               
                   
               
               
                  6481 
                 gcagtaggtg cttaatatgt tttgaggcaa ggtcttgctc tgttgcacat gctggagtgc 
               
               
                   
               
               
                  6541 
                 agtggcacaa tcgtaattca ttgcagcctt gaactcctga gctcaagtga tcctcctgcc 
               
               
                   
               
               
                  6601 
                 tcagcctcct gagtagctgg gactacaggc atgcaccacc aagcttggct aatttaaaaa 
               
               
                   
               
               
                  6661 
                 aaaaattata tagataggga cttgctatgt tgcctaggct gatcttgaac tcctaacctc 
               
               
                   
               
               
                  6721 
                 aagcaatcct cccacctcgg ccttccaaag tgctgggata ataggcatgg agccgccaca 
               
               
                   
               
               
                  6781 
                 cccagccaat gtgccgaaga aagaaagaaa aacatgctca tcctttgagt caggttcaaa 
               
               
                   
               
               
                  6841 
                 ttttttctcc tctttaaccc ccagtcactc cagttataag tgatttttaa ctcttctcac 
               
               
                   
               
               
                  6901 
                 actttaatgc atctggcaag aagatccacg tggtgttagg aacaatacag gaccttaagg 
               
               
                   
               
               
                  6961 
                 atgggggaat cagcaggtgt cagcgtgccc tgtatgctca gggcagctgt ttccactgga 
               
               
                   
               
               
                  7021 
                 cattctccct ttgcctctct gggcagcaac tcctaggcca gccgacctgc tgtgtcgagt 
               
               
                   
               
               
                  7081 
                 aaccaggatt tctcaatctt ggcatggttg ccattttgga ccagatcgtt ctttgttgtg 
               
               
                   
               
               
                  7141 
                 ggggctgccc tgtacggcaa agaatgccga gcagcacttc cagtctccac ccacaggacg 
               
               
                   
               
               
                  7201 
                 ccagtagcac cctctaagtt gtgagaactc aaaatgtccc cagaggatgc cagatgtccc 
               
               
                   
               
               
                  7261 
                 ctggggtggg gacacaatca ccccaggttg agatccatgg agccaggtct gtttgccacc 
               
               
                   
               
               
                  7321 
                 aaggggtaaa gctccattcc caccttagga gggctaggag gcagcatcgt ggggccacag 
               
               
                   
               
               
                  7381 
                 aaggcctggg tttgcagtca gaggacagga tgcacattcc ttcaagatac agacccagat 
               
               
                   
               
               
                  7441 
                 tgttgggcat ctagttcttg ggttttctgt tgttgctgtt ccgttttgtc tgtcttccct 
               
               
                   
               
               
                  7501 
                 cctttgttta ctagcagcct ggaatttgcc actttttcta aacgaagatt tatggaacac 
               
               
                   
               
               
                  7561 
                 ttaccacacg gctgacgctg cgcgaggcta aggttctaat acaccgcagc tcacttaact 
               
               
                   
               
               
                  7621 
                 ctcgcaatac cataaacgca cactgtttca tcttgaccct ttcttgggaa ggtgacagag 
               
               
                   
               
               
                  7681 
                 aggtaggagg gcaaacatct tgtgtgcccc gtcccaaggg tattactggt ggaataatat 
               
               
                   
               
               
                  7741 
                 ccgcccccca ccccagtttc taatttgctg taggctgtga cgctgtgggg caagactagg 
               
               
                   
               
               
                  7801 
                 agtcctgttg aaattaggaa taagtgtgct gtgagggaag ggctgcctta ttttagagca 
               
               
                   
               
               
                  7861 
                 cagattttct gaatatctat tttgacaggt tcgatcctct ccccttcctg ccttccttct 
               
               
                   
               
               
                  7921 
                 gtcgattttc aatgtcttga tggtgtccca cctgagtggc ctttagagat gtgagttgtg 
               
               
                   
               
               
                  7981 
                 aggcactggg gaggcaggca cacgtcctcc agcccaagac tgcctaattt aacagggatt 
               
               
                   
               
               
                  8041 
                 tctgcattct ggaacaagcc tccattttcc ccaagcagga ttactccaga gggcaaaaca 
               
               
                   
               
               
                  8101 
                 cagcccaata gtatcacatt tcctttctgc tttagcaaaa ataaccactg tctcattcat 
               
               
                   
               
               
                  8161 
                 gggaaaaggc cgccaaacaa atttgttact ggaaccattt gtaacaactt ctagtttgca 
               
               
                   
               
               
                  8221 
                 ctgccttgga gcaagcacac tttgtagagg agggatttgc agttacttgg gcaacaaggt 
               
               
                   
               
               
                  8281 
                 aaccactgat cattacagga agcttcagaa accgtgggac cagtgtagaa gaatggacta 
               
               
                   
               
               
                  8341 
                 tctgtccaaa ctaagaataa aaagaatgac acttgtattt tgtatgtctt tttcactttg 
               
               
                   
               
               
                  8401 
                 cctttctagt aattcatttt tcttgatatt tacaccttgt ggccctgtga tagactggaa 
               
               
                   
               
               
                  8461 
                 atctcaaaaa cacacgttca gcaccaagat tttcagcagc accgcctcag aatgagaccc 
               
               
                   
               
               
                  8521 
                 ctagaaaaaa ctgcgtgttt tccacttgcc caacacgagg agtttttgga acacgacctg 
               
               
                   
               
               
                  8581 
                 cttgaggtgg agattttcta gatgggcaaa gagaaggaaa cacttaacct aggaagagta 
               
               
                   
               
               
                  8641 
                 tttaggaaga agaaagaaca cagcctttct gcacaggaaa ccgccgagca gaggggcatc 
               
               
                   
               
               
                  8701 
                 tggcctctgc agtggcctcc aaatagagtc caatggctgg ggccagcgtg gctgcttaaa 
               
               
                   
               
               
                  8761 
                 ggggactcaa gggatataat aaaatgcaga ttctcaggtc ctagtgcaga caggctcacc 
               
               
                   
               
               
                  8821 
                 caataagtct ggactgcata tgggaatctc tatttctagg cccttctgca aggtattcct 
               
               
                   
               
               
                  8881 
                 gctctttcca ggaaccatcg gcagctggtt tggggaaaga agcaacgact ccaagtgtga 
               
               
                   
               
               
                  8941 
                 cctgtgagct ggcagcagcc accctcagct ctgctctcgg tcactgaatc cgattctgca 
               
               
                   
               
               
                  9001 
                 ttttaacagg accccaggtg ttgcacccac acaaagctga agcagattgg tctgggggca 
               
               
                   
               
               
                  9061 
                 aaaaattaga gctatggaga ttctctcaaa tgaaatagat gatatcattg actgttagag 
               
               
                   
               
               
                  9121 
                 cttctagaag gaatctgagg tcacttgttc aaattccctg atttacagat gaggaaacag 
               
               
                   
               
               
                  9181 
                 aggctcagac agctcaaatg acttctctcc aatacccaac attcgacaag tagcagctct 
               
               
                   
               
               
                  9241 
                 gggactagta cccaaagcac ctagctctcc aatcactgcg caagccacac aattctgtct 
               
               
                   
               
               
                  9301 
                 gcttgtcagt ggcttttctg attcaaaaaa agcttaggaa tttccccagg aggcagcacg 
               
               
                   
               
               
                  9361 
                 atgtagtggg aagggctctg gatgtctctc caaggcttct ggaattcatg cccacctcca 
               
               
                   
               
               
                  9421 
                 ccaagaagcc actttcctgc cagctacagg tgctcacctg aaaagcaagc cagaccatat 
               
               
                   
               
               
                  9481 
                 taaccctggc attgctggta cctggaagac tttctgattc aatgctttcc acctcctcct 
               
               
                   
               
               
                  9541 
                 acccctcacc acccccgtgg catgaaatcc tgggggctgc tttagaaatt gttttctttg 
               
               
                   
               
               
                  9601 
                 gctgctggtg ggggtgctgc tggtgggggt ttgcacagct ggcacactgc accagtctgg 
               
               
                   
               
               
                  9661 
                 tgggggtttg cacagctggc acactgcacc agtctcctgc ctgctgccaa caaggccatt 
               
               
                   
               
               
                  9721 
                 tcccaagcac tggctttgga gaagttgggg ctctgaagtg ggaacacaag gctgcctttt 
               
               
                   
               
               
                  9781 
                 gcaggccagg tgtaaattct ccccctgcca ctttcagcct agcgtgaaac agatggagtg 
               
               
                   
               
               
                  9841 
                 tgcattccca cttcccttta tggtaccctg gaatgatgga gctgcccagg gcatcgccac 
               
               
                   
               
               
                  9901 
                 gttactctct agacagtctc tttgtcttcc tgcaatggca gcgccgaggt tgtatatttc 
               
               
                   
               
               
                  9961 
                 taggtgcagg tatatgattg ccatataata aaaatctgaa aacatccca 
               
               
                   
               
            
           
           
               
            
               
                 PSG7 mRNA transcript 2046 bp 
               
               
                 SEQ ID NO: 7 
               
            
           
           
               
               
            
               
                     1 
                 agtgcagaag gaggaaggac agcacagctg acagccgtgc tcaggaagat tctggatcct 
               
               
                   
               
               
                    61 
                 aggctcatct ccacagagga gaacacgcag ggagcagaga ccatggggcc cctctcagcc 
               
               
                   
               
               
                   121 
                 cctccctgca cacagcatat aacctggaaa gggctcctgc tcacagcatc acttttaaac 
               
               
                   
               
               
                   181 
                 ttctggaacc cgcccaccac agcccaagtc acgattgaag cccagccacc aaaagtttcc 
               
               
                   
               
               
                   241 
                 gaggggaagg atgttcttct acttgtccac aatttgcccc agaatcttac tggctacatc 
               
               
                   
               
               
                   301 
                 tggtacaaag gacaaatcag ggacctctac cattatgtta catcatatat agtagacggt 
               
               
                   
               
               
                   361 
                 caaataatta aatatgggcc tgcatacagt ggacgagaaa cagtatattc caatgcatcc 
               
               
                   
               
               
                   421 
                 ctgctgatcc agaatgtcac ccaggaagac acaggatcct acactttaca catcataaag 
               
               
                   
               
               
                   481 
                 cgaggtgatg ggactggagg agtaactgga cgtttcacct tcaccttata cctggagact 
               
               
                   
               
               
                   541 
                 cccaaaccct ccatctccag cagcaatttc aaccccaggg aggccacgga ggctgtgatt 
               
               
                   
               
               
                   601 
                 ttaacctgtg atcctgagac tccagatgca agctacctgt ggtggatgaa tggtcagagc 
               
               
                   
               
               
                   661 
                 ctccctatga ctcacagctt gcagctgtct gaaaccaaca ggaccctcta cctatttggt 
               
               
                   
               
               
                   721 
                 gtcacaaact atactgcagg accctatgaa tgtgaaatac ggaacccagt gagtgccagc 
               
               
                   
               
               
                   781 
                 cgcagtgacc cagtcaccct gaatctcctc ccgaagctgc ccaagcccta catcaccatc 
               
               
                   
               
               
                   841 
                 aataacttaa accccaggga gaataaggat gtctcaacct tcacctgtga acctaagagt 
               
               
                   
               
               
                   901 
                 gagaactaca cctacatttg gtggctaaat ggtcagagcc tcccggtcag tcccagggta 
               
               
                   
               
               
                   961 
                 aagcgacgca ttgaaaacag gatcctcatt ctacccagtg tcacgagaaa tgaaacagga 
               
               
                   
               
               
                  1021 
                 ccctatcaat gtgaaatacg ggaccgatat ggtggcatcc gcagtgaccc agtcaccctg 
               
               
                   
               
               
                  1081 
                 aatgtcctct atggtccaga cctccccaga atttaccctt cattcaccta ttaccattca 
               
               
                   
               
               
                  1141 
                 ggacaaaacc tctacttgtc ctgctttgcg gactctaacc caccggcaca gtattcttgg 
               
               
                   
               
               
                  1201 
                 acaattaatg ggaagtttca gctatcagga caaaagcttt ctatccccca gattactaca 
               
               
                   
               
               
                  1261 
                 aagcatagcg ggctctatgc ttgctctgtt cgtaactcag ccactggcaa ggaaagctcc 
               
               
                   
               
               
                  1321 
                 aaatccgtga cagtcagagt ctctgactgg acattaccct gaattctact agttcctcca 
               
               
                   
               
               
                  1381 
                 attccatctt ctcccatgga acctcaaaga gcaagaccca ctctgttcca gaagccctat 
               
               
                   
               
               
                  1441 
                 aagtcagagt tggacaactc aatgtaaatt tcatgggaaa atccttgtac ctgatgtctg 
               
               
                   
               
               
                  1501 
                 agccactcag aactcaccaa aatgttcaac accataacaa cagctgctca aactgtaaac 
               
               
                   
               
               
                  1561 
                 aaggaaaaca agttgatgac ttcacactgt ggacagcttt tcccaagatg tcagaataag 
               
               
                   
               
               
                  1621 
                 actccccatc atgatgaggc tctcacccct cttagctgtc cttgcttgtg cctgcctctt 
               
               
                   
               
               
                  1681 
                 tcacttggca ggataatgca gtcattagaa tttcacatgt agtataggag cttctgaggg 
               
               
                   
               
               
                  1741 
                 taacaacaga gtgtcagata tgtcatctca acctcagact tttacataac atctcaggag 
               
               
                   
               
               
                  1801 
                 gaaatgtggc tctctccatc ttgcatacag ggctcccaat agaaatgaac acagagatat 
               
               
                   
               
               
                  1861 
                 tgcctgtgtg tttgcagaga agatggtttc tataaagagt aggaaagctg aaattatagt 
               
               
                   
               
               
                  1921 
                 agactcccct ttaaatgcac attgtgtgga tggctctcac catttcctaa gagatacatt 
               
               
                   
               
               
                  1981 
                 gtaaaacgtg acagtaagac tgattctagc agaataaaac atgtactaca tttgctaaaa 
               
               
                   
               
               
                  2041 
                 aaaaaa 
               
               
                   
               
            
           
           
               
            
               
                 PAPPA mRNA transcript 11025 bp 
               
               
                 SEQ ID NO: 8 
               
            
           
           
               
               
            
               
                     1 
                 gagcatcttt tggggggagg gaattcagcg gatcagtctt aagaggagct tttttttgaa 
               
               
                   
               
               
                    61 
                 gcgagaaatc atataaaata aaatgaaata aaacaaggag gaaggcaacc agctgttagg 
               
               
                   
               
               
                   121 
                 ggaaaaataa ggcagataaa ggagcgggga gagaaattaa ttgccaacca ggaggagttg 
               
               
                   
               
               
                   181 
                 ggctgtattt ttcaaaggtg gggagagtgg agcacacacc ttgaggagga aagcgagaaa 
               
               
                   
               
               
                   241 
                 gaaaagaaaa aagcaagtgg aaaggggggc tcgcccaaga agggtgaaga agcgaagaaa 
               
               
                   
               
               
                   301 
                 gtcgaggcgc cgaggctccc aaagctggca gctccgggtg gcggtgcagg ggcgaagggg 
               
               
                   
               
               
                   361 
                 gggcgggggg aaccgtcgga catgcggctc tggagttggg tgctgcacct ggggctgctg 
               
               
                   
               
               
                   421 
                 agcgccgcgc tgggctgcgg gctggccgag cgtccccgcc gggcccggag agacccgcgg 
               
               
                   
               
               
                   481 
                 gccggccgac ccccgcgccc cgccgccggc ccggccacct gcgccacccg ggcggcccgc 
               
               
                   
               
               
                   541 
                 ggccgccgcg cctcgccgcc gccgccgccg ccgccgggcg gtgcctggga agccgtgcgc 
               
               
                   
               
               
                   601 
                 gtcccccggc ggcggcagca gcgggaggcg aggggcgcca ccgaggagcc gagcccgccg 
               
               
                   
               
               
                   661 
                 agccgggcgc tctatttcag cgggcgaggc gagcagctgc gcctccgggc cgacctcgag 
               
               
                   
               
               
                   721 
                 ctgccccggg acgcgttcac gctgcaagtg tggctgcgag cggagggggg ccagaggtct 
               
               
                   
               
               
                   781 
                 ccggcagtga tcacagggct gtatgacaaa tgttcttata tctcacgtga ccgaggatgg 
               
               
                   
               
               
                   841 
                 gtcgtgggca ttcacaccat cagtgaccaa gacaacaaag acccacgcta ctttttctcc 
               
               
                   
               
               
                   901 
                 ttgaagacag accgagcccg gcaagtgacc accatcaatg cccaccgcag ctacctccca 
               
               
                   
               
               
                   961 
                 ggccagtggg tatacctagc tgccacctat gatgggcagt tcatgaagct ctatgtgaat 
               
               
                   
               
               
                  1021 
                 ggtgcccagg tggccacctc tggggaacaa gtgggtggca tattcagccc actgacccag 
               
               
                   
               
               
                  1081 
                 aagtgcaaag tgctcatgtt agggggcagt gccctgaatc acaactaccg gggctacatc 
               
               
                   
               
               
                  1141 
                 gagcacttca gtctgtggaa ggtggccagg actcagcggg agatactgtc tgacatggaa 
               
               
                   
               
               
                  1201 
                 acccatggcg cccacactgc tctacctcag ctcctcctcc aggagaactg ggacaatgtg 
               
               
                   
               
               
                  1261 
                 aagcatgcct ggtcccccat gaaggatggc agcagcccca aagtggaatt cagcaatgcc 
               
               
                   
               
               
                  1321 
                 cacggctttc tgctggacac gagtctggag cctcctctgt gcggacagac attgtgtgac 
               
               
                   
               
               
                  1381 
                 aacacagagg tcattgccag ctacaatcag ctctcaagtt tccgccagcc caaggtggtg 
               
               
                   
               
               
                  1441 
                 cgctaccgcg tggtcaacct ctatgaagat gatcataaga acccgacggt gacgcgcgag 
               
               
                   
               
               
                  1501 
                 caggtggact tccagcacca tcagctggct gaggccttca agcaatacaa catctcctgg 
               
               
                   
               
               
                  1561 
                 gagctggacg tgctggaggt gagcaactcc tcccttcgcc gccgcctcat cctggccaac 
               
               
                   
               
               
                  1621 
                 tgtgacatca gcaagattgg ggatgagaac tgtgaccccg agtgcaacca cacgctgacg 
               
               
                   
               
               
                  1681 
                 ggccacgacg gcggggattg ccgccacctg cgccaccctg ccttcgtgaa gaagcagcac 
               
               
                   
               
               
                  1741 
                 aacggggtgt gtgacatgga ctgcaactat gaacggttca actttgatgg tggagagtgc 
               
               
                   
               
               
                  1801 
                 tgtgaccctg aaatcaccaa tgtcactcag acttgctttg accccgactc tccacacaga 
               
               
                   
               
               
                  1861 
                 gcctacttgg atgttaatga gctgaagaac attcttaaat tggatggatc aacacatctc 
               
               
                   
               
               
                  1921 
                 aatattttct ttgcaaaatc ctcagaggag gagttggcag gagtagcaac ttggccatgg 
               
               
                   
               
               
                  1981 
                 gacaaggagg ccctgatgca cttaggtggc attgtcttga acccatcttt ctatggcatg 
               
               
                   
               
               
                  2041 
                 cctgggcaca cccacaccat gatccatgag attggtcaca gcctgggcct ctatcacgtc 
               
               
                   
               
               
                  2101 
                 ttccgaggca tctcagaaat ccagtcctgc agtgacccct gcatggagac agagccctcc 
               
               
                   
               
               
                  2161 
                 ttcgagactg gagacctctg caatgatacc aacccagccc ctaaacacaa gtcctgtggt 
               
               
                   
               
               
                  2221 
                 gacccagggc caggaaatga cacctgtggc tttcatagct tcttcaacac tccttacaac 
               
               
                   
               
               
                  2281 
                 aacttcatga gctatgcaga tgacgactgt acggactcct tcacgcccaa tcaagtcgcc 
               
               
                   
               
               
                  2341 
                 agaatgcact gttacctgga cctggtctac cagggctggc agccctccag gaaaccagcg 
               
               
                   
               
               
                  2401 
                 cctgttgccc tcgcccccca agttctgggc cacacaacgg actctgtgac actggagtgg 
               
               
                   
               
               
                  2461 
                 ttcccaccta tagatggcca tttctttgaa agagaattgg gatcagcatg tcatctttgc 
               
               
                   
               
               
                  2521 
                 ctggaaggga gaatcctggt gcagtatgct tccaacgctt cctccccaat gccctgcagc 
               
               
                   
               
               
                  2581 
                 ccatcaggac actggagccc tcgtgaagca gaaggtcatc ctgatgttga acagccctgt 
               
               
                   
               
               
                  2641 
                 aagtccagtg tccgcacctg gagcccaaat tcagctgtca acccacacac ggttcctcca 
               
               
                   
               
               
                  2701 
                 gcctgccctg agcctcaagg ctgctacctc gagctggagt tcctctaccc cttggtccct 
               
               
                   
               
               
                  2761 
                 gagtctctga ccatttgggt gacctttgtc tccactgact gggactctag tggagctgtc 
               
               
                   
               
               
                  2821 
                 aatgacatca aactgttggc tgtcagtggg aagaacatct ccctgggtcc tcagaatgtc 
               
               
                   
               
               
                  2881 
                 ttctgtgatg tcccactgac catcagactc tgggacgtgg gcgaggaggt gtatggcatc 
               
               
                   
               
               
                  2941 
                 caaatctaca cgctggatga gcacctggag atcgatgctg ccatgttgac ctccactgca 
               
               
                   
               
               
                  3001 
                 gacaccccac tctgtctaca gtgtaagccc ctgaagtata aggtggtccg ggaccctcct 
               
               
                   
               
               
                  3061 
                 ctccagatgg atgtggcctc catcctacat ctcaatagga aattcgtaga catggatcta 
               
               
                   
               
               
                  3121 
                 aatcttggca gtgtgtacca gtattgggtc ataactattt caggaactga agagagtgag 
               
               
                   
               
               
                  3181 
                 ccatcacctg ctgtcacata catccatgga agtgggtact gtggcgatgg cattatacaa 
               
               
                   
               
               
                  3241 
                 aaagaccaag gtgaacaatg cgacgacatg aataagatca atggtgatgg ctgctccctt 
               
               
                   
               
               
                  3301 
                 ttctgccgac aagaagtctc cttcaattgt attgatgaac ccagccggtg ctatttccat 
               
               
                   
               
               
                  3361 
                 gatggtgatg gggtatgtga ggagtttgaa caaaaaacca gcattaagga ctgtggtgtc 
               
               
                   
               
               
                  3421 
                 tacacgcccc agggattcct ggatcagtgg gcatccaatg cttcagtatc tcatcaagac 
               
               
                   
               
               
                  3481 
                 cagcaatgcc caggctgggt catcatcgga cagccagcag catcccaggt gtgtcgaacc 
               
               
                   
               
               
                  3541 
                 aaggtgatag atctcagtga aggcatttcc cagcatgcct ggtacccttg caccatcagc 
               
               
                   
               
               
                  3601 
                 tacccatatt cccagctggc tcagaccact ttttggctcc gggcgtattt ttctcaacca 
               
               
                   
               
               
                  3661 
                 atggttgccg cagctgtcat tgtccacctg gtgacggatg ggacatatta tggggaccaa 
               
               
                   
               
               
                  3721 
                 aagcaggaga ccatcagcgt gcagctgctt gataccaaag atcagagcca cgatctaggc 
               
               
                   
               
               
                  3781 
                 ctccatgtcc tgagctgcag gaacaatccc ctgattatcc ctgtggtcca tgacctcagc 
               
               
                   
               
               
                  3841 
                 cagcccttct accacagcca ggcggtacgt gtgagcttca gttcgcccct ggtcgccatc 
               
               
                   
               
               
                  3901 
                 tcgggggtgg ccctccgttc cttcgacaac tttgaccccg tcaccctgag cagctgccag 
               
               
                   
               
               
                  3961 
                 agaggggaga cctacagccc tgccgagcag agctgcgtgc acttcgcatg tgagaaaact 
               
               
                   
               
               
                  4021 
                 gactgtccag agctggctgt ggagaatgct tctctcaatt gctccagcag cgaccgctac 
               
               
                   
               
               
                  4081 
                 cacggtgccc agtgtactgt gagctgccgg acaggctacg tgctccagat acggcgggat 
               
               
                   
               
               
                  4141 
                 gatgagctga tcaagagcca gacgggaccc agcgtcacag tgacctgtac agagggcaag 
               
               
                   
               
               
                  4201 
                 tggaataagc aggtggcctg tgagccagtc gactgcagca tcccagatca ccatcaagtc 
               
               
                   
               
               
                  4261 
                 tatgctgcct ccttctcctg ccctgagggc accacctttg gcagtcaatg ttccttccag 
               
               
                   
               
               
                  4321 
                 tgccgtcacc ctgcacaatt gaaaggcaac aacagcctcc tgacctgcat ggaggatggg 
               
               
                   
               
               
                  4381 
                 ctgtggtcct tcccagaggc cctgtgtgag ctcatgtgcc tcgctccacc ccctgtgccc 
               
               
                   
               
               
                  4441 
                 aatgcagacc tccagaccgc ccggtgccga gagaataagc acaaggtggg ctccttctgc 
               
               
                   
               
               
                  4501 
                 aaatacaaat gcaagcctgg ataccatgtg cctggatcct ctcggaagtc aaagaaacgg 
               
               
                   
               
               
                  4561 
                 gccttcaaga ctcagtgtac ccaggatggc agctggcagg agggagcttg tgttcctgtg 
               
               
                   
               
               
                  4621 
                 acctgtgacc cacctccacc aaaattccat gggctctacc agtgtactaa tggcttccag 
               
               
                   
               
               
                  4681 
                 ttcaacagtg agtgtaggat caagtgtgaa gacagtgatg cctcccaggg acttgggagc 
               
               
                   
               
               
                  4741 
                 aatgtcattc attgccggaa agatggcacc tggaacggct ccttccatgt ctgccaggag 
               
               
                   
               
               
                  4801 
                 atgcaaggcc agtgctcggt tccaaacgag ctcaacagca acctcaaact gcagtgccct 
               
               
                   
               
               
                  4861 
                 gatggctatg ccatagggtc ggagtgtgcc acctcgtgcc tggaccacaa cagcgagtcc 
               
               
                   
               
               
                  4921 
                 atcatcctgc caatgaacgt gaccgtgcgt gacatccccc actggctgaa ccccacacgg 
               
               
                   
               
               
                  4981 
                 gtagagagag ttgtctgcac tgctggtctc aagtggtatc ctcaccctgc tctgattcac 
               
               
                   
               
               
                  5041 
                 tgtgtcaaag gctgtgagcc cttcatggga gacaattatt gtgatgccat caacaaccga 
               
               
                   
               
               
                  5101 
                 gccttttgca actatgacgg tggggattgc tgcacctcca cagtgaagac caaaaaggtc 
               
               
                   
               
               
                  5161 
                 accccattcc ctatgtcctg tgatctacaa ggtgactgtg cttgtcggga cccccaggcc 
               
               
                   
               
               
                  5221 
                 caagaacaca gccggaaaga cctccgggga tacagccatg gctaaggaag gacaagaagt 
               
               
                   
               
               
                  5281 
                 tgtcaaagaa ttcccaacgc caggacccac atccctttgg tattgatttc acagtcagct 
               
               
                   
               
               
                  5341 
                 gctcaacgga atggcctctc cacaccaggg atccttagca cccaaccggt ctgcctttaa 
               
               
                   
               
               
                  5401 
                 ttttacccag gaaggactca cattggggcg aatgaaccaa gtttcgccat gctggatgat 
               
               
                   
               
               
                  5461 
                 gaaatggatt cccatcccaa agtctgagat ggattgcata tacagtgtgc agtcccagag 
               
               
                   
               
               
                  5521 
                 cctcctaaaa ttctagccat ttgtcacaca accacagcaa gaaacgtgtt ctatatctag 
               
               
                   
               
               
                  5581 
                 agtgtgccca tctgtgttta gtacacatgc atgcatacac acccatacaa acatctgtgt 
               
               
                   
               
               
                  5641 
                 gagggcagtt ctggagatga gcagagagag accggaataa actcaatctt ttctttccca 
               
               
                   
               
               
                  5701 
                 agctcctagc caacactatc cttgggagaa agaaatttgc agaaactgct aagaccaagt 
               
               
                   
               
               
                  5761 
                 gtggagatgt caagctagtt cacactctga ggctcagaat atgtaggaca tgcacaattg 
               
               
                   
               
               
                  5821 
                 tgcagtcctt tgggattgga agtgaaacag tctgtgatcc cctaccttct agggaactag 
               
               
                   
               
               
                  5881 
                 gacctaggaa gaggtaaaga ttatcaggta tgcaaagcgc cccaattctt ctgctgccat 
               
               
                   
               
               
                  5941 
                 gggggatttt accccaactc cagggttcga ggccaatctg agaatggctt aggattgcaa 
               
               
                   
               
               
                  6001 
                 tgtcaaggta ttatatcagc cccttgcttg aggcttgagg tcataatatc cctctaggac 
               
               
                   
               
               
                  6061 
                 ttacctgttc ccccagatct tgccttggga ccacatttgc tgctactttt cctgctgctc 
               
               
                   
               
               
                  6121 
                 tatcctatac attgaataat ccaagatggt agaactaggt taggaaaaat tccacacaac 
               
               
                   
               
               
                  6181 
                 caaacagtct gccttaaaag tgacccacat ttttccatag ctcctcactt tttagccctt 
               
               
                   
               
               
                  6241 
                 ctgcaagaga aaaaccctca tgggtccaca tggtgagaag ttaagtttcc tgtaagtggg 
               
               
                   
               
               
                  6301 
                 cctctcaccc tggaaaggag ttgagggaca tcagatgctg gaaccctcac tgaaagtcca 
               
               
                   
               
               
                  6361 
                 gaatgtctaa gccagtgtta gattttgtaa acaagtggaa cagtgttaaa tttctatgat 
               
               
                   
               
               
                  6421 
                 gttggagcca tccagagact actggaattg tcgagacttt tggattatta tccttatcct 
               
               
                   
               
               
                  6481 
                 tatcctaatc ttcctagccc ttcaggctag agtaggcttc gatcctgaga accttgctgt 
               
               
                   
               
               
                  6541 
                 tgctctgagg agatataatt ctgggagaaa gaatctttta taagaacagt acagattgtt 
               
               
                   
               
               
                  6601 
                 ctcaagaggg ccatcagaag gaagccaaag agttcacagc ctcagcacca acaactcaac 
               
               
                   
               
               
                  6661 
                 atggtcatca tgttttctat atggtttttc cagctagcag tactcccttc catacctgtg 
               
               
                   
               
               
                  6721 
                 actgggcagt gcttttctct ctcccatgtc tagcctccaa aagttaagtg aaaattagtc 
               
               
                   
               
               
                  6781 
                 aactgcacgt ggaagccccc accactttgg ggatctcttt atttcttttc agccagggac 
               
               
                   
               
               
                  6841 
                 ctgtccactc cctttgaatt aatatgggaa gaaattaata caggatgaac tggagagaag 
               
               
                   
               
               
                  6901 
                 ggttgagtgt ggcatacttt ctgaaacctg gagctgggaa ttgcggagaa gggaaggtct 
               
               
                   
               
               
                  6961 
                 agactagtta catcacatag ggattactgt aaatcaagtc atctcaagtc tagtgaagac 
               
               
                   
               
               
                  7021 
                 agccaacaga aacaaaacct agcataggga tagaaaatac catgcacgtg tgcagcccca 
               
               
                   
               
               
                  7081 
                 cctaattcct gcatccaagg caggtgttgt taatctatca tagcacttaa aaaaaaaaaa 
               
               
                   
               
               
                  7141 
                 aaaaagagac caaaaataac tttaggaacc accatattat atcactccca atagcactga 
               
               
                   
               
               
                  7201 
                 cctggtgatc aaaaacactt gagaagacat ctattggcca tctctggcca attacactaa 
               
               
                   
               
               
                  7261 
                 gaaacatatc aaggtgcttt tggcacaggt gcccacaaat acggatgcag tgctgagata 
               
               
                   
               
               
                  7321 
                 gtttatgaga cttgtaccat ttcacaaact ctgaaattgg gttccatatt ggcaaggctg 
               
               
                   
               
               
                  7381 
                 ccacagttgt taagaataat cctctatgtt tcttcctcac aaaaccatat ctcatttata 
               
               
                   
               
               
                  7441 
                 tccagaccat tacttcacta taattacaag gacaaattat tagcaagaaa taagaatagt 
               
               
                   
               
               
                  7501 
                 attagaagaa ttgatcctat tttgaacccc tctccagtat cttcacactc ttgtcaactc 
               
               
                   
               
               
                  7561 
                 tccaggcctc tctcttgccc tgagttatca gcctgtgtgg tgttaactac cttagaaggt 
               
               
                   
               
               
                  7621 
                 acaagctaag aaatgtaaca gtatcaaccc tcccagttgc ttaattatac ccataggtaa 
               
               
                   
               
               
                  7681 
                 tacaaaaagc tctgaagacc caaagatgac attactaatg atgtgatttc aggagccaca 
               
               
                   
               
               
                  7741 
                 gaagaacctt accagcttcc ctcaaatcag tccttatcct ctttctatct tcactcccat 
               
               
                   
               
               
                  7801 
                 catcatctat tttcacacta tccagctaag caaagattcc tggaggctga cttgtatctt 
               
               
                   
               
               
                  7861 
                 cagactcaca gagtgaattc agctcttctg aatcaagacc cacccagtct ctttcattca 
               
               
                   
               
               
                  7921 
                 gacctgttgc taacaaattt atatttgcca aggatattag gcaaaagagg ctacttgatt 
               
               
                   
               
               
                  7981 
                 ggtggccaac ctcgtgccca catggaaggt atctttaata gggtcttttc aaaccttagt 
               
               
                   
               
               
                  8041 
                 ggaggagggt cagctcaatt tgggcaatgc atttgttccc agtttcattt tcttcctggg 
               
               
                   
               
               
                  8101 
                 aattaactcg tcatttcatt ccttcagtca tcttctgtgt aggtgaccgg agcactgaga 
               
               
                   
               
               
                  8161 
                 ggcagctctg atgcactatt gtgtgtcagc agctcaaagg ccctaaaaca ctgaaggttc 
               
               
                   
               
               
                  8221 
                 tgcatctgaa gtattagatt gttagcagca aaatatgaaa gatgaggtgg acagtcctct 
               
               
                   
               
               
                  8281 
                 aagccctatt tagggaagct tttccaagcc acaatcttaa ctacctaccc aaaggatttg 
               
               
                   
               
               
                  8341 
                 cattaccccc agattctgtg ccaacaacct tttaaggaaa tacagtcctt gggaaatgag 
               
               
                   
               
               
                  8401 
                 ttttgatggt gaattggggt gttaaggaag ggaaagattg tcatagatgg tagggctttg 
               
               
                   
               
               
                  8461 
                 aaaatgcagg gtatcagctg ccactcctgg cttcaacaca ttgagtcact gcctagacgg 
               
               
                   
               
               
                  8521 
                 ttctcttggt cttattccca tcctggccaa tgcttaaata ctatttgttg aaaataattc 
               
               
                   
               
               
                  8581 
                 tttgagacag atttcagcta cctcccttcc aggttcgatt taacttggtt gtaattgtca 
               
               
                   
               
               
                  8641 
                 atttgttgtt ataggtctta cctgtgtgaa agaaagaaaa agaaagaaag aaagaaagag 
               
               
                   
               
               
                  8701 
                 aaaggaaatt ataaggtcaa gttaacagtt ttgaggtttt gtgttttttt ctggaactac 
               
               
                   
               
               
                  8761 
                 ttcaagtgag aaaataaaaa aaaatggtga caaagctgta cagatagaga taatagaaga 
               
               
                   
               
               
                  8821 
                 caaagagatt aaaaggaaat aaaaatgcat gattaaaaac taagaataaa aaacctattt 
               
               
                   
               
               
                  8881 
                 ttatgtttcc taaaggaaat tgtttattct acagcctcag taggtagaca caaacataaa 
               
               
                   
               
               
                  8941 
                 gatttcccta gaagacatag agtgggattt gataacactg tctgttattt tctgtacatt 
               
               
                   
               
               
                  9001 
                 gtggtaggtc caggaaatat gacattttcc cccttgatgt gttattgttg ttgttgggtg 
               
               
                   
               
               
                  9061 
                 gggtgggcat tttgtttatt tgtttggtgg caatcagtgg tagtagggag tgggagggct 
               
               
                   
               
               
                  9121 
                 tatattggtt tttccagcta ttaaggggac atattgtgtc gttgtgcttt tcacgttata 
               
               
                   
               
               
                  9181 
                 aaatgtttat atttaccagt acagcactgg gctttataaa gactgcactc agaaccacac 
               
               
                   
               
               
                  9241 
                 tgcacagtcc agttttttaa aaagctgcta catgacagac aggtaatccc actgagtgag 
               
               
                   
               
               
                  9301 
                 ttttgagaaa caaatcaaac gaagtaaaca agaaacataa aaaccaaata gcaaatgaat 
               
               
                   
               
               
                  9361 
                 aaaagcctgt tcttgtaact tattcaactt ttgccaaatt cctaccaatc acttgctttt 
               
               
                   
               
               
                  9421 
                 taaaagaaat gtataatagc caaaagagaa attatgtccc tgttgtacag aagttagaat 
               
               
                   
               
               
                  9481 
                 ttttgactcc aggcagcagt ttgctcagtg atcttgaaca agttatccaa ttgcctctac 
               
               
                   
               
               
                  9541 
                 atttgcatca gtttctctag ctgcaaaatg gggataatac tatataccta cctcacagtg 
               
               
                   
               
               
                  9601 
                 ggagggcagg agattttgag gccctgaggt tttaggtggg ctgtgagggc caacgcttga 
               
               
                   
               
               
                  9661 
                 cacaaagtcc atgggttatt attcaagaat gcacaggccc atcggccttt tagaaagaca 
               
               
                   
               
               
                  9721 
                 agacagggag tgcttgtttg atatttcaag gaataaagcc ggagctcctg aattgtagtc 
               
               
                   
               
               
                  9781 
                 caccttaaaa gagagacctg tattggagaa tattttattt ttttggcaaa tttgatctta 
               
               
                   
               
               
                  9841 
                 ccctttacca gttctataat ttggttaaaa gctgattatg tcctacaatg tcaaagtcag 
               
               
                   
               
               
                  9901 
                 ctaactgtcg tctacttaag acttctggtc atttccaact tatagaggaa gggagtctct 
               
               
                   
               
               
                  9961 
                 aaaatctctt cttcagaagg cacctcactt ctcagactta aaattccaca tcaagtgttc 
               
               
                   
               
               
                 10021 
                 cattaaaaga agataaggca ttctgagtgc aaacaaatgg gggcttctta aactacacac 
               
               
                   
               
               
                 10081 
                 cagcagtcag tgaggaaaac tttgaacaat tattgagttg ctttcttggg tctctataat 
               
               
                   
               
               
                 10141 
                 caataacctg tctgcagata tctatctata taaagatatt atatataaat ataaatttac 
               
               
                   
               
            
           
           
               
               
               
            
               
                 10201 
                 atatatatgc acatgtatat atagttgtac atatatgtgt gtatatatat acttaaatgt 
                   
               
               
                   
               
            
           
           
               
               
            
               
                 10261 
                 aatatttaca aaataaaact gtgatctcgt ctagagaaaa tgtattcata ttacaaactg 
               
               
                   
               
               
                 10321 
                 ctcttccata tttatgtacc atattatacc tttttattat tgttataatt attatgggta 
               
               
                   
               
               
                 10381 
                 tttctaatta atatgatgtt gaaacctgtt tggcaccttc tggaagctac caaaaaaatg 
               
               
                   
               
               
                 10441 
                 acactccatt gaagtgctta aaagctgttc tcataagaat tctactggcc tattgtaaaa 
               
               
                   
               
               
                 10501 
                 aagaaaaaaa aaaagaaaaa gaagaaagac acaaagaaaa taatctaaac accaaaaact 
               
               
                   
               
               
                 10561 
                 aaacacaatt ccaatccttt ttctgtacct cacgcgcata aatttgctgc tcctattttt 
               
               
                   
               
               
                 10621 
                 ttttctgttt atgtgttttt atggatctaa gttaaatctt ttggcaatat ataaaaatgt 
               
               
                   
               
               
                 10681 
                 aaatagtaaa ctttatttat taagaatgtc atctttttta atttatattt acacaattgt 
               
               
                   
               
               
                 10741 
                 tcatctaatt tattttttct atacagtttt aaatactcag acatattttg ctgttcatga 
               
               
                   
               
               
                 10801 
                 tatttttatc ctgttctcat ggatttgttt tcccatactg ttttctctga tctcaattac 
               
               
                   
               
               
                 10861 
                 aggttggatc tcacaaataa taatgtcaga gacagaaata ttttgccact gttgattact 
               
               
                   
               
               
                 10921 
                 atactttaaa gttctatatt atgaaaatat ataatagctt gtacgcttca aaaaaaaaaa 
               
               
                   
               
               
                 10981 
                 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 
               
               
                   
               
            
           
           
               
            
               
                 LGALS14 mRNA transcript 794 bp 
               
               
                 SEQ ID NO: 9 
               
            
           
           
               
               
            
               
                     1 
                 gctgcattac agacacagac ctgcaaacat ctatggttgt gacagagttt ctttctgaca 
               
               
                   
               
               
                    61 
                 cctgagtctt tctcctgctg cacggaaagc ttgctgggag gggcttggaa tctggcatga 
               
               
                   
               
               
                   121 
                 agccaaaggg catctctgag ttgcagcatt taaatgatcc cactcagaga ttcacacaga 
               
               
                   
               
               
                   181 
                 agactggaca caattccgaa gagctgccca gaaggagaga acaatgtcat cactacccgt 
               
               
                   
               
               
                   241 
                 accatacaca ctgcctgttt ccttgcctgt tggttcgtgc gtgataatca cagggacacc 
               
               
                   
               
               
                   301 
                 gatcctcact tttgtcaagg acccacagct ggaggtgaat ttctacactg ggatggatga 
               
               
                   
               
               
                   361 
                 ggactcagat attgctttcc aattccgact gcactttggt catcctgcaa tcatgaacag 
               
               
                   
               
               
                   421 
                 ttgtgtgttt ggcatatgga gatatgagga gaaatgctac tatttaccct ttgaagatgg 
               
               
                   
               
               
                   481 
                 caaaccattt gagctgtgca tctatgtgcg tcacaaggaa tacaaggtaa tggtaaatgg 
               
               
                   
               
               
                   541 
                 ccaacgcatt tacaactttg cccatcgatt cccgccagca tctgtgaaga tgctgcaagt 
               
               
                   
               
               
                   601 
                 cttcagagat atctccctga ccagagtgct tatcagcgat tgagggagat gatcagactc 
               
               
                   
               
               
                   661 
                 ctcattgttg aggaatccct ctttctacct gaccatggga ttcccagagc ctactaacag 
               
               
                   
               
               
                   721 
                 aataatccct cctcacccct tcccctacac ttgatcatta aaacagcacc aaacttcaaa 
               
               
                   
               
               
                   781 
                 aaaaaaaaaa aaaa 
               
               
                   
               
            
           
           
               
            
               
                 CLCN3 mRNA transcript 6299 bp 
               
               
                 SEQ ID NO: 10 
               
            
           
           
               
               
            
               
                     1 
                 gtgacgtcac gcgtcgacgc tggggcgtac ctttcgggct cctgactcct gccgcttctc 
               
               
                   
               
               
                    61 
                 ttccccttcc gtgggtcagg gccggtccgg tccggaacct gcagcccctt tcccagtgtt 
               
               
                   
               
               
                   121 
                 ctagttcgcc cgtgacccgg aataatgagc aaggagggtg tggtgggttg aaagccatcc 
               
               
                   
               
               
                   181 
                 tactttactc ccgagttaga gcatggattc agttttagtc ttaaggggga agtgagattg 
               
               
                   
               
               
                   241 
                 gagattttta tttttaattt tgggcagaag caggttgact ctagggatct ccagagcgag 
               
               
                   
               
               
                   301 
                 aggatttaac ttcatgttgc tcccgtgttt gaaggaggac aataaaagtc ccaccgggca 
               
               
                   
               
               
                   361 
                 aaattttcgt aacctctgcg gtagaaaacg tcaggtatct tttaaatcgc gatagttttc 
               
               
                   
               
               
                   421 
                 gctgtgtcag gctttcttcg gtggagctcc gagggtagct aggttctagg tttgaaacag 
               
               
                   
               
               
                   481 
                 atgcagaatc caaaggcagc gcaaaaaaca gccaccgatt ttgctatgtc tctgagctgc 
               
               
                   
               
               
                   541 
                 gagataatca gacagctaaa tggagtctga gcagctgttc catagaggct actatagaaa 
               
               
                   
               
               
                   601 
                 cagctacaac agtataacaa gtgcaagtag tgatgaggaa cttttagatg gagcaggtgt 
               
               
                   
               
               
                   661 
                 tattatggac tttcaaacat ctgaagatga caatttatta gatggtgaca ctgcagttgg 
               
               
                   
               
               
                   721 
                 aactcattat acaatgacaa atggaggcag cattaacagt tctacacatt tactggatct 
               
               
                   
               
               
                   781 
                 tttggatgaa ccaattccag gtgttggtac atatgatgat ttccatacta ttgattgggt 
               
               
                   
               
               
                   841 
                 gcgagaaaaa tgtaaagaca gagaaaggca tagacggatc aacagcaaaa agaaagaatc 
               
               
                   
               
               
                   901 
                 agcatgggaa atgacaaaaa gtttgtatga tgcgtggtca ggatggctag tagtaacact 
               
               
                   
               
               
                   961 
                 aacaggattg gcatcagggg cactggccgg attaatagac attgctgccg attggatgac 
               
               
                   
               
               
                  1021 
                 tgacctaaag gagggcattt gccttagtgc gttgtggtac aaccacgaac agtgctgttg 
               
               
                   
               
               
                  1081 
                 gggatctaat gaaacaacat ttgaagagag ggataaatgt ccacagtgga aaacatgggc 
               
               
                   
               
               
                  1141 
                 agaattaatc ataggtcaag cagagggtcc tggttcttat atcatgaact acataatgta 
               
               
                   
               
               
                  1201 
                 catcttctgg gccttgagtt ttgcctttct tgcagtttcc ctggtaaagg tatttgctcc 
               
               
                   
               
               
                  1261 
                 atatgcctgt ggctctggaa ttccagagat taaaactatt ttaagtggat tcatcatcag 
               
               
                   
               
               
                  1321 
                 aggttacttg ggaaaatgga ctttaatgat taaaaccatc acattagtcc tggctgtggc 
               
               
                   
               
               
                  1381 
                 atcaggtttg agtttaggaa aagaaggtcc cctggtacat gttgcctgtt gctgcggaaa 
               
               
                   
               
               
                  1441 
                 tatcttttcc tacctctttc caaagtatag cacaaacgaa gctaaaaaaa gggaggtgct 
               
               
                   
               
               
                  1501 
                 atcagctgcc tcagctgcag gggtttctgt agcttttggt gcaccaattg gaggagttct 
               
               
                   
               
               
                  1561 
                 ttttagcctg gaagaggtta gctattattt tcctctcaaa actttatgga gatcattttt 
               
               
                   
               
               
                  1621 
                 tgctgcttta gtggctgcat ttgttttgag gtccatcaat ccatttggta acagccgtct 
               
               
                   
               
               
                  1681 
                 ggtccttttt tatgtggagt atcatacacc atggtacctt tttgaactgt ttccttttat 
               
               
                   
               
               
                  1741 
                 tcttctaggg gtatttggag ggctttgggg agcctttttc attagggcaa atattgcctg 
               
               
                   
               
               
                  1801 
                 gtgtcgtcga cgcaagtcca cgaaatttgg aaagtatccc gttctggaag tcattattgt 
               
               
                   
               
               
                  1861 
                 tgcagccatt actgctgtga tagccttccc taatccatac actaggctaa acaccagtga 
               
               
                   
               
               
                  1921 
                 actgatcaaa gagcttttta cagactgtgg tcccctggaa tcctcttctc tttgtgacta 
               
               
                   
               
               
                  1981 
                 cagaaatgac atgaatgcca gtaaaattgt cgatgacatt cctgatcgtc cagcaggcat 
               
               
                   
               
               
                  2041 
                 tggagtatat tcagctatat ggcagttatg cctggcactc atatttaaaa tcataatgac 
               
               
                   
               
               
                  2101 
                 agtattcact tttggcatca aggttccatc aggcttgttc atccccagca tggccattgg 
               
               
                   
               
               
                  2161 
                 agcgatcgca ggaaggattg tggggattgc ggtggagcag cttgcctact atcaccacga 
               
               
                   
               
               
                  2221 
                 ctggtttatc tttaaggagt ggtgtgaggt cggggctgat tgcattacac ctggccttta 
               
               
                   
               
               
                  2281 
                 tgccatggtt ggtgctgctg catgcttagg tggtgtgaca agaatgactg tctccctggt 
               
               
                   
               
               
                  2341 
                 ggttattgtt tttgagctta ctggaggctt ggaatatatt gttcccctta tggctgcagt 
               
               
                   
               
               
                  2401 
                 catgaccagt aaatgggttg gagatgcctt tggcagggaa ggcatttatg aagcacacat 
               
               
                   
               
               
                  2461 
                 ccgattaaat ggataccctt tcttggatgc aaaagaagaa ttcactcata ccaccctggc 
               
               
                   
               
               
                  2521 
                 tgctgacgtt atgagacctc gaaggaatga tcctccctta gctgtcctga cacaggacaa 
               
               
                   
               
               
                  2581 
                 tatgacagtg gatgatatag aaaacatgat taatgaaacc agctacaatg gatttcctgt 
               
               
                   
               
               
                  2641 
                 cataatgtca aaagaatctc agagattagt gggatttgcc ctcagaagag acctgacaat 
               
               
                   
               
               
                  2701 
                 tgcaatagaa agtgccagga aaaaacaaga aggtatcgtt ggcagttctc gggtgtgttt 
               
               
                   
               
               
                  2761 
                 tgcacagcac accccatctc ttccagcaga aagtcctcgg ccattgaagc ttcgaagcat 
               
               
                   
               
               
                  2821 
                 tcttgacatg agccctttta cagtgacaga ccacacccca atggagatcg tggtggatat 
               
               
                   
               
               
                  2881 
                 tttccgaaag ctgggactga ggcagtgcct tgtaactcac aatgggattg tcttggggat 
               
               
                   
               
               
                  2941 
                 catcacaaag aagaacatat tagagcatct cgagcaacta aagcagcacg tcgaaccctt 
               
               
                   
               
               
                  3001 
                 ggcgcctcct tggcattata acaaaaaaag atatcctccg gcatatggcc cagacggcaa 
               
               
                   
               
               
                  3061 
                 accaagaccc cgcttcaata atgttcaact gaatctcaca gatgaggaga gagaagaaac 
               
               
                   
               
               
                  3121 
                 ggaagaggaa gtttatttgt tgaatagcac aactctttaa cctgagggag tcatctactt 
               
               
                   
               
               
                  3181 
                 ttttttcctc ctttacaaaa aaagaaagga aatataaaag ccgggttttt gcaacatggt 
               
               
                   
               
               
                  3241 
                 ttgcaaataa tgctggtgga atggaggagt tgtttgggga gggaaaggag agagaaggaa 
               
               
                   
               
               
                  3301 
                 aggagtgagg tatttcccgt ctaacagaaa gcagcgtatc aactcctatt gttctgcact 
               
               
                   
               
               
                  3361 
                 ggatgcattc agctgaggat gtgcctgata gtgcaggctt gcgcctcaac agagatgaca 
               
               
                   
               
               
                  3421 
                 gcagagtcct cgagcacctg gcctgttgct ccaacattgc aaagacacat tatcagtccc 
               
               
                   
               
               
                  3481 
                 tatttctaga gggattactt tgaattgagc catctataaa actgcaaggt cttgcccttt 
               
               
                   
               
               
                  3541 
                 tttttaatca aaactgttct gtttaattca tgaattgtat agttaagcat tacctttcta 
               
               
                   
               
               
                  3601 
                 cattccagaa gagcctttat ttctctctct ctctctctct ctctctctct ctctactgag 
               
               
                   
               
               
                  3661 
                 ctgtaacaaa gcctctttaa atcggtgtat ccttttgaag cagtcctttc tcatattgag 
               
               
                   
               
               
                  3721 
                 atgtactgtg attttactga ggtttcatca caagaaggga gtgtttcttg tgccattaac 
               
               
                   
               
               
                  3781 
                 catgtagttt gtaccatcac taaatgcttg gaacagtaca catgcaccac aacaaaggct 
               
               
                   
               
               
                  3841 
                 catcaaacag gtaaagtctc gaaggaagcg agaacgaaat ctctcattgt gtgccgtgtg 
               
               
                   
               
               
                  3901 
                 gctcaaaacc gaaaacaatg aagcttggtt ttaaaggata aagttttctt ttttgttttc 
               
               
                   
               
               
                  3961 
                 ctctcagact ttatggataa tgtgaccggg tcttatgcaa attttctatt tctaaaacta 
               
               
                   
               
               
                  4021 
                 ctactatgat atacaagtgc tgttgagcat aattaaataa aatgctgctg ctttgacagt 
               
               
                   
               
               
                  4081 
                 aaagagaagg aagtattctg attagctgta tctggtatta attgcatgtt aaaacactgg 
               
               
                   
               
               
                  4141 
                 aatttttaaa attgaaatta gatcagtcat tcttttcttt tctcaagata tctcatggct 
               
               
                   
               
               
                  4201 
                 gacactgaag aagaaatgta attcataact tgcactaaat gtatattttt tttcttaaaa 
               
               
                   
               
               
                  4261 
                 atttaccatt cttatttata tttttatgga ttaaaattta taaaatacag atcagttaat 
               
               
                   
               
               
                  4321 
                 attgcactta agtaatttta cctttttaat gtgattttta tagaataatt cagacttaca 
               
               
                   
               
               
                  4381 
                 aatacagaga tatgaacaaa gtttacagtg ggaacaaagg tttaaaaaaa ggttgtggtt 
               
               
                   
               
               
                  4441 
                 ctctctctgt gatccagtgt gcacataaac ctttctctga tctttcactg ccatcctctg 
               
               
                   
               
               
                  4501 
                 gattatgtct tctgacctgt ccattttgac ccattaactg gaaagttgaa aaactacatt 
               
               
                   
               
               
                  4561 
                 aactggaaag ttgaaaaact acattacttt ggagaataaa accgaaagtt cgtgtatacc 
               
               
                   
               
               
                  4621 
                 ttcttaaaaa aaaaatcaaa ccaaaaatgt gaaaacaata gaattgcaaa gatagcagtt 
               
               
                   
               
               
                  4681 
                 aaaattttaa tctgaaaata acctttgaat ctcgggctag gttacgtcca tatttgaagt 
               
               
                   
               
               
                  4741 
                 ggtcagtgat ggtttgaaca ttttttgcag gatgagtgaa aatgcactgg attatatttg 
               
               
                   
               
               
                  4801 
                 ggatttttgt ttttggaatt gtctgtttta atcacagcct taattcacaa ttggcaaagg 
               
               
                   
               
               
                  4861 
                 cagtttactc aaaggactgg gctaaatatt ctgtaattat gcatttttga taggaaaatg 
               
               
                   
               
               
                  4921 
                 aaatttttgc aaacagacat tttctttttt tttggctgga gtgcagtggg gcatggtctt 
               
               
                   
               
               
                  4981 
                 ggctcactgc agcgttgacc acctgggctc aagtgatact cccgcctcag ccacccaagt 
               
               
                   
               
               
                  5041 
                 agctggcact acgggcacac gccaccatgc ccagctaatt tttttgtatt tttagtagag 
               
               
                   
               
               
                  5101 
                 atggggtttt gccatgctgc ccaggctggt ctcaactcct cagctcaagc aatctgcctg 
               
               
                   
               
               
                  5161 
                 cgtgagcctc ccaaagtggt ggaattacag gcgtgggcca ctgcgcctgg cccagacaga 
               
               
                   
               
               
                  5221 
                 cattttctga aacacaactg gcaatgagct gtttttacat tttgaaagtg attcttcact 
               
               
                   
               
               
                  5281 
                 tcctagttct taattatagt atacctatta agatctgtaa gatcctgaag acataagatc 
               
               
                   
               
               
                  5341 
                 atgaagccat ataagaatga ggattgaaag ttgagcaaaa ttttcgggat tttgggaaac 
               
               
                   
               
               
                  5401 
                 attcttagct gtgctatctg cctaaaatta ttccttatta cttctctcct ttgacagact 
               
               
                   
               
               
                  5461 
                 tcaagttttc ttcatagccc tttcaaagtt ttttgagcca tccagagtaa aatcatttct 
               
               
                   
               
               
                  5521 
                 aaatgatagt tctgtatatc tccaactcgt cttaagtgta tttgcctgtg tgcaacgtat 
               
               
                   
               
               
                  5581 
                 tgctagacta tgaactcctc agcatggctg ctggataact taattgtcct gagttaatag 
               
               
                   
               
               
                  5641 
                 ccttcaaagg acaaatcggt ttctttgcag atagcttcgt aaaacttcac atggagttta 
               
               
                   
               
               
                  5701 
                 ttttatcata tttccctttt ttatttctgc tcctccttta attgcccatc ttgcttcaga 
               
               
                   
               
               
                  5761 
                 gactgacatt tcagggtgga tattaattaa agcattaatt ttgttttttg gtatatttct 
               
               
                   
               
               
                  5821 
                 atccctagta tttctatctt actgctaaaa tacaggaaaa gtgccgtatt tttaatgcat 
               
               
                   
               
               
                  5881 
                 ttagtggttt tctttggtgt tatctgttcc atttttcttt ttcatacatt gaagtgtgtc 
               
               
                   
               
               
                  5941 
                 tccttttcaa ccaaaataat gaaatagtgg agaccatgaa attgttgtgc ctggctaatt 
               
               
                   
               
               
                  6001 
                 ggcaaattaa tttaccaata taataagtgt agcgccttgt ttgaataccc tttttgagaa 
               
               
                   
               
               
                  6061 
                 ggtatgatga gaatgggcaa gggtgtcagc atctcttctt cttaataatt aattgttttc 
               
               
                   
               
               
                  6121 
                 agttttggtt cacgaagaat gcttagttaa tctgtaatgt tgcctagagc tgtatttatc 
               
               
                   
               
               
                  6181 
                 tgtttttatt tatactagtg tagtaaagct gcatatcatt acagtaaaaa cgactactgt 
               
               
                   
               
               
                  6241 
                 gatgagttaa tcagaaaatc tattaaaatc tatatgacaa tgaaaaaaaa aaaaaaaaa 
               
               
                   
               
            
           
           
               
            
               
                 DAPP1 mRNA transcript 3006 bp 
               
               
                 SEQ ID NO: 11 
               
            
           
           
               
               
            
               
                     1 
                 gcaggctgct gtctcacaga gcgagaaggt gtcaggagca gcccagttgt gtctctctct 
               
               
                   
               
               
                    61 
                 ctacctctgt gaagggcgcg aatgggcaga gcagaacttc tagaagggaa gatgagcacc 
               
               
                   
               
               
                   121 
                 caggatccct cagatctgtg gagcagatcc gatggagagg ctgagctgct ccaggacttg 
               
               
                   
               
               
                   181 
                 gggtggtatc acggcaacct cacacgccat gctgctgaag ctcttctcct ctcaaatgga 
               
               
                   
               
               
                   241 
                 tgtgacggca gctaccttct gagggacagc aatgagacca ccgggctgta ctctctctct 
               
               
                   
               
               
                   301 
                 gtgagggcca aagattctgt taaacacttt catgttgaat atactggata ttcatttaaa 
               
               
                   
               
               
                   361 
                 tttggcttta atgaattctc atctttgaag gattttgtca agcattttgc aaatcagcct 
               
               
                   
               
               
                   421 
                 ttgattggaa gcgagacagg cactctgatg gttctaaaac atccctaccc aagaaaagtg 
               
               
                   
               
               
                   481 
                 gaagaaccct ccatttatga atctgtccgg gttcacacag caatgcagac aggaagaaca 
               
               
                   
               
               
                   541 
                 gaagatgacc ttgtgcccac agcaccttct ctgggcacca aagaaggtta cctcaccaaa 
               
               
                   
               
               
                   601 
                 cagggaggcc tggtcaagac ctggaaaaca agatggttta ctctgcacag gaatgaactg 
               
               
                   
               
               
                   661 
                 aaatacttca aagaccagat gtcaccagaa ccaattcgga tcctagacct aacagaatgt 
               
               
                   
               
               
                   721 
                 tcagctgtac aattcgatta ttcacaagaa agggtaaact gtttttgttt ggtatttcca 
               
               
                   
               
               
                   781 
                 ttcaggacat tttatctctg tgcaaagacc ggagtagaag ctgatgagtg gatcaagata 
               
               
                   
               
               
                   841 
                 ttacgctgga aattggtcaa ggacaaaagc tgatttattt tgtctgctct ctgtatatct 
               
               
                   
               
               
                   901 
                 cccgaggaga agactgatca caaataagaa aacagctcaa ccaaggggaa ggcacgatcc 
               
               
                   
               
               
                   961 
                 gatctcggtc gttcatcttt aaatagatct ttcttgccaa ggaatgctct ggcccaggag 
               
               
                   
               
               
                  1021 
                 caaggtggaa tgtttccctg acgctgtgat ctgcagcagg cttcaaatga aaaccgacta 
               
               
                   
               
               
                  1081 
                 aggattttct ttcaaaaaca aatcagaagc agatgctgat tgggacccat ataccacgtt 
               
               
                   
               
               
                  1141 
                 gctgactcac gttgctgccc ttccatgatg ttgccatctc cttgagaaca ctgaagcaat 
               
               
                   
               
               
                  1201 
                 caccattctg atagaaagtg cttaaaccac cactcttagg tctgctcact cttagaacac 
               
               
                   
               
               
                  1261 
                 acaatggaag aggaagggtt tttgttttca ctcattgtgg tccccaagcc tattgacact 
               
               
                   
               
               
                  1321 
                 agttgcctag agtcccactg tgagtcatgg tcagcctgtc tgacatccag gttgtgctat 
               
               
                   
               
               
                  1381 
                 taaccaagaa ggaaacagat acttggaggc ttagatgact tctgcaggat ttatattcag 
               
               
                   
               
               
                  1441 
                 atagaaaaca tcaaatattt tcaggggaga ggtttttttt tttaattttt ccccctttat 
               
               
                   
               
               
                  1501 
                 acaaaaaaaa aagaacattt ccaaaactaa aatagaaaat gcttgtggca tttattttct 
               
               
                   
               
               
                  1561 
                 ctttttaaaa ggttcagaaa tttggcaggt cctttgcttc taatgacaaa actgtgagag 
               
               
                   
               
               
                  1621 
                 ctagatgtcc tatgggcaat taggtagtat aataaaggta aatgaaggta caatttttaa 
               
               
                   
               
               
                  1681 
                 accattattt tcaccctgtt ggggtaaatg ttttaaagag tgagaaaaca taaattgaga 
               
               
                   
               
               
                  1741 
                 aagggtgata aagtaataga taacttttag tttaataata attattgtta ttatactact 
               
               
                   
               
               
                  1801 
                 aataatagag cacttgtaag cactaagtta tctttatcca acatttctcc aaatggactg 
               
               
                   
               
               
                  1861 
                 aaagaaactt ttcaaggaca gtgtattata acaatccctt tcccagaatt agttgtatag 
               
               
                   
               
               
                  1921 
                 ggttggccca agagatgtaa gaaaaatctc gcattgctcc ctaagcaccc tgggccttat 
               
               
                   
               
               
                  1981 
                 taaagagcaa cttctatttc cagtcggggg agtaacacta aagctacaag aaatatgtaa 
               
               
                   
               
               
                  2041 
                 taatgatagg taataatgtg ttccaaagct ttttcaaact agaataagga ggcaaataga 
               
               
                   
               
               
                  2101 
                 agaatgagat actgatgtcc acagttcatt ggcagaatct aaccccttct gttatctttt 
               
               
                   
               
               
                  2161 
                 ttaatactat ttttgtttag atagaagttt caaagaagat aaaaatgctt gaagagcctg 
               
               
                   
               
               
                  2221 
                 agagtaaaaa gattatgctg caaagctatg atataaactg ctcttgcagt ccaaagggat 
               
               
                   
               
               
                  2281 
                 acctgattaa agaagtttct tatttaaaca tctcagacgc aaaaattaca ttaaattttt 
               
               
                   
               
               
                  2341 
                 gtatatttca acaacatttt aaatgtattt tgttatgttt gtattatata ggataaagca 
               
               
                   
               
               
                  2401 
                 aatgtcaagt taaaatgtat tgtgttgttt gtaaagtaag aagttactgg ccaggagcgg 
               
               
                   
               
               
                  2461 
                 cggctcatgc ctgtaatccc aggactttgg taggccaaga caagcagatc acttgaggtc 
               
               
                   
               
               
                  2521 
                 aggagttcaa catcagcctg gccaacatga tgaaaccttg tctttactaa aaatacaaaa 
               
               
                   
               
               
                  2581 
                 attagctggg catggtggca ggcgcctgta atcccagcta ctcaggaggc tgaggcagga 
               
               
                   
               
               
                  2641 
                 gaattgcttg aacccgggag gtggaggttg cagtgaacca agatcgcggc gctgcactct 
               
               
                   
               
               
                  2701 
                 agcctgggtg acagagtcag actccgtccc aaaaaaacaa acaaacaaaa caaaacaaaa 
               
               
                   
               
               
                  2761 
                 aaaaacagaa gttacaaatg aatactcacg gatatgtata gttttatgtt tgttttctta 
               
               
                   
               
               
                  2821 
                 gaaacaaatg tgtttctttg ggtgggtaat attgtgtttt actatgttta ccttttataa 
               
               
                   
               
               
                  2881 
                 aacataacct gtttatttat attctttggc tttgtttatt aaaaagcatg attttgctgt 
               
               
                   
               
               
                  2941 
                 gcatgtacca ttttgctatt aaaatttatt tttaatattt gtaacttgaa aaaaaaaaaa 
               
               
                   
               
               
                  3001 
                 aaaaaa 
               
               
                   
               
            
           
           
               
            
               
                 POLE2 mRNA transcript 1861 bp 
               
               
                 SEQ ID NO: 12 
               
            
           
           
               
               
            
               
                     1 
                 agcctactcg gtccggggtt gcgaactgta aggtctgagt tgctgcggcg caggcagcgg 
               
               
                   
               
               
                    61 
                 agaccaagca gggatcttaa cagggtttag cgccacgcgg gccagggccg aggccggagc 
               
               
                   
               
               
                   121 
                 tgggaggggc gcgcccggga aggggcggag ctgcggcggt ggcgccaaat cgcaaatatg 
               
               
                   
               
               
                   181 
                 gcgccggagc ggctgcggag ccgggcgctc tccgccttca agttgcgggg cttgctgctc 
               
               
                   
               
               
                   241 
                 cgtggtgaag ctattaagta cctcacagaa gctcttcagt ctatcagtga attagagctt 
               
               
                   
               
               
                   301 
                 gaagataaac tggaaaagat aattaatgca gttgagaagc aacccttgtc atcaaacatg 
               
               
                   
               
               
                   361 
                 attgaacgat ctgtggtgga agcagcagtc caggaatgca gtcagtctgt tgatgaaact 
               
               
                   
               
               
                   421 
                 atagagcacg ttttcaatat cataggagca tttgatattc cacgctttgt gtacaattca 
               
               
                   
               
               
                   481 
                 gaaagaaaaa aatttcttcc tctgttaatg accaaccacc ctgcaccaaa tttatttgga 
               
               
                   
               
               
                   541 
                 acaccaagag ataaagcaga gatgtttcgt gagcgatata ccattttgca ccagaggacc 
               
               
                   
               
               
                   601 
                 cacaggcatg aattatttac tcctccggtg ataggttctc accctgatga aagcggaagc 
               
               
                   
               
               
                   661 
                 aaattccagc ttaaaacaat agaaacctta ttgggtagta caaccaaaat cggagatgcg 
               
               
                   
               
               
                   721 
                 attgttcttg gaatgataac gcagttaaaa gagggaaaat tttttctgga agatcctact 
               
               
                   
               
               
                   781 
                 ggaacagtcc aactagacct tagtaaagct cagttccata gtggtttata cacagaggca 
               
               
                   
               
               
                   841 
                 tgctttgtct tagcagaagg ttggtttgaa gatcaagtgt ttcatgtcaa tgcctttgga 
               
               
                   
               
               
                   901 
                 tttccaccca ctgagccctc tagtactact agggcatact atggaaatat taattttttt 
               
               
                   
               
               
                   961 
                 ggaggtcctt ctaatacatc tgtgaagact tctgcaaaac taaaacagct agaagaggag 
               
               
                   
               
               
                  1021 
                 aataaagatg ctatgtttgt gtttttatct gatgtttggt tggaccaggt ggaagtattg 
               
               
                   
               
               
                  1081 
                 gaaaaacttc gcataatgtt tgctggttat tcaccagcac ctccaacctg ctttattctg 
               
               
                   
               
               
                  1141 
                 tgtggtaatt tttcatctgc accatatgga aaaaatcaag ttcaagcttt gaaagattcc 
               
               
                   
               
               
                  1201 
                 ctaaaaactt tggcagatat aatatgtgaa tacccagata ttcaccaaag tagtcgtttt 
               
               
                   
               
               
                  1261 
                 gtgtttgtac ctggtccaga ggatcctgga tttggttcca tcttaccaag gccaccactt 
               
               
                   
               
               
                  1321 
                 gctgaaagca tcactaatga attcagacaa agggtaccat tttcagtttt tactactaat 
               
               
                   
               
               
                  1381 
                 ccttgcagaa ttcagtactg tacacaggaa attactgtct tccgtgaaga cttagtaaat 
               
               
                   
               
               
                  1441 
                 aaaatgtgca gaaactgcgt ccgttttcct agcagcaatt tggctattcc taatcacttt 
               
               
                   
               
               
                  1501 
                 gtaaagacta tcttatccca aggacatctg actcccctac ctctttatgt ctgcccagtg 
               
               
                   
               
               
                  1561 
                 tattgggcat atgactatgc tttgagagtg tatcctgtgc ccgatctact tgtcattgca 
               
               
                   
               
               
                  1621 
                 gacaaatatg atcctttcac tacgacaaat accgaatgcc tctgcataaa ccctggctct 
               
               
                   
               
               
                  1681 
                 tttccaagaa gtggattttc attcaaagtt ttttatcctt ctaataagac agtagaagat 
               
               
                   
               
               
                  1741 
                 agcaaacttc aaggcttttg agattcttaa agatcatctg aagaaaattc atcagttttc 
               
               
                   
               
               
                  1801 
                 tgcttaactc tatatcttat gtgattctga tattacaata aaattatggt aaactttagg 
               
               
                   
               
               
                  1861 
                 a 
               
               
                   
               
            
           
           
               
            
               
                 PPBP mRNA transcript 1307 bp 
               
               
                 SEQ ID NO: 13 
               
            
           
           
               
               
            
               
                     1 
                 acttatctgc agacttgtag gcagcaactc accctcactc agaggtcttc tggttctgga 
               
               
                   
               
               
                    61 
                 aacaactcta gctcagcctt ctccaccatg agcctcagac ttgataccac cccttcctgt 
               
               
                   
               
               
                   121 
                 aacagtgcga gaccacttca tgccttgcag gtgctgctgc ttctgccatt gctgctgact 
               
               
                   
               
               
                   181 
                 gctctggctt cctccaccaa aggacaaact aagagaaact tggcgaaagg caaagaggaa 
               
               
                   
               
               
                   241 
                 agtctagaca gtgacttgta tgctgaactc cgctgcacgt gtataaagac aacctctgga 
               
               
                   
               
               
                   301 
                 attcatccca aaaacatcca aagtttggaa gtgatcggga aaggaaccca ttgcaaccaa 
               
               
                   
               
               
                   361 
                 gtcgaagtga tagccacact gaaggatggg aggaaaatct gcctggaccc agatgctccc 
               
               
                   
               
               
                   421 
                 agaatcaaga aaattgtaca gaaaaaattg gcaggtgatg aatctgctga ttaatttgtt 
               
               
                   
               
               
                   481 
                 ctgtttctgc caaacttctt taactcccag gaagggtaga attttgaaac cttgattttc 
               
               
                   
               
               
                   541 
                 tagagttctc atttattcag gatacctatt cttactgcat taaaatttgg atatgtgctt 
               
               
                   
               
               
                   601 
                 cattctgcct caaaaatcac attttattct gagaaggctg gttaaaagat ggcagaaaga 
               
               
                   
               
               
                   661 
                 agatgaaaat aaataagcct ggtttcaacc ctctaattct tgcctaaaca ttggactgta 
               
               
                   
               
               
                   721 
                 ctttgcactt ttttctttaa aaatttctat tctaacacaa cttggttgat ttttcctggt 
               
               
                   
               
               
                   781 
                 ctactttatg gttattagac atactcatgg gtattattag atttcataat ggtcaatgat 
               
               
                   
               
               
                   841 
                 aataggaatt acatggagcc caacagagaa tatttgctca atacattttt gttaatatat 
               
               
                   
               
               
                   901 
                 ttaggaactt aatggagtct ctcagtgtct tagtcctagg atgtcttatt taaaatactc 
               
               
                   
               
               
                   961 
                 cctgaaagtt tattctgatg tttattttag ccatcaaaca ctaaaataat aaattggtga 
               
               
                   
               
               
                  1021 
                 atatgaacct tataaactgt ggctagccgg tttaaagcga atatattcgc cactagtaga 
               
               
                   
               
               
                  1081 
                 acaaaaatag atgatgaaaa tgaattaaca tatctacata gttataattc tatcattaga 
               
               
                   
               
               
                  1141 
                 atgagcctta taaataagta caatatagga cttcaacctt actagactcc taattctaaa 
               
               
                   
               
               
                  1201 
                 ttctactttt ttcatcaaca gaactttcat tcatttttta aaccctaaaa cttataccca 
               
               
                   
               
               
                  1261 
                 cactattctt acaaaaatat tcacatgaaa taaaaatttg ctattga 
               
               
                   
               
            
           
           
               
            
               
                 LYPLAL1 mRNA transcript 1922 bp 
               
               
                 SEQ ID NO: 14 
               
            
           
           
               
               
            
               
                     1 
                 gtgcgcggcc ccgcgcggca acgcaggggc ggaaccgcat gactggcagt ggcatcagcg 
               
               
                   
               
               
                    61 
                 atggcggctg cgtcggggtc ggctctgcag cgctgtatcg tgtcgccggc agggaggcat 
               
               
                   
               
               
                   121 
                 agcgcctctc tgatcttcct gcatggctca ggtgattctg gacaaggatt aagaatgcgg 
               
               
                   
               
               
                   181 
                 atcaagcagg ttttaaatca agatttaaca ttccaacaca taaaaattat ttatccaaca 
               
               
                   
               
               
                   241 
                 gctcctccca gatcatacac tcctatgaaa ggaggaacct ccaatgtatg gtttgacaga 
               
               
                   
               
               
                   301 
                 tttaaaataa ccaatgactg cccagaacac cttgaatcaa ttgatgtcat gtgtcaagtg 
               
               
                   
               
               
                   361 
                 cttactgatt tgattgatga agaagtaaaa agtggcatca agaagaacag gatattaata 
               
               
                   
               
               
                   421 
                 ggaggattct ctatgggagg atgcatggca atacatttag catatagaaa tcatcaagat 
               
               
                   
               
               
                   481 
                 gtggcaggag tatttgctct ttctagtttt ctgaataaag catctgctgt ttaccaggct 
               
               
                   
               
               
                   541 
                 cttcagaaga gtaatggtgt acttcctgaa ttatttcagt gtcatggtac tgcagatgag 
               
               
                   
               
               
                   601 
                 ttagttcttc attcttgggc agaagagaca aactcaatgt taaaatctct aggagtgacc 
               
               
                   
               
               
                   661 
                 acgaagtttc atagttttcc aaatgtttac catgagctaa gcaaaactga gttagacata 
               
               
                   
               
               
                   721 
                 ttgaagttat ggattcttac aaagctgcca ggagaaatgg aaaaacaaaa atgaatgaat 
               
               
                   
               
               
                   781 
                 caagagtgat ttgttaatgt aagtgtaatg tctttgtgaa aagtgatttt tactgccaaa 
               
               
                   
               
               
                   841 
                 ttataatgat aattaaaata ttaagaaata acactttcct gactttttta ttattaaaat 
               
               
                   
               
               
                   901 
                 gcttatcact gtagacagta gctaatctta ttaatgaaaa acaatagaca aacatctgtg 
               
               
                   
               
               
                   961 
                 cataattttt cagacacaat tctgtaaata tttggaaacc ttttaagtat ttaaactttt 
               
               
                   
               
               
                  1021 
                 aaatttttga aataaagtat tctaaactaa tataaataag gacaatgaaa aaacatgaaa 
               
               
                   
               
               
                  1081 
                 ggacttagca taatgttatt ttatcttttc tacaactttg tttaaattac ctttccaaag 
               
               
                   
               
               
                  1141 
                 atatttgtgt ttatgtaatt ttccacggaa taacattaat actctaggtt tataaaccgg 
               
               
                   
               
               
                  1201 
                 tttcacatta tttcatttga tcatcacaag agctttgcga agtaagccga gaagttgtta 
               
               
                   
               
               
                  1261 
                 ctggtattta ataatagcaa tagaggagtt aaagactttc ccacagcttg caggtcaaga 
               
               
                   
               
               
                  1321 
                 caagaaattc aggtctccta attctcagtg gagctctatt tctgttaacc caaattgctg 
               
               
                   
               
               
                  1381 
                 ctctgtttta ggcctcaatt tcatctgtaa aatgatacta atagtactta tcccattgga 
               
               
                   
               
               
                  1441 
                 tttttgttga gatttaaata aatagccaaa agccaataca taataaacac tcaataaaga 
               
               
                   
               
               
                  1501 
                 ttaaccacaa ggagagtcat gatctggctc caggaataca ttgttagatg actgaaaaat 
               
               
                   
               
               
                  1561 
                 tgtattactt caatgaaaat actataaata ataacatttt cacatattag ttggttctca 
               
               
                   
               
               
                  1621 
                 tgcatacata atctaatttt atttgatcct cacaactgtt taagttttat taaatataca 
               
               
                   
               
               
                  1681 
                 ttatccctat ttgtataaat agaatcatac aatacctgcc tgctttcatt caacaaaatt 
               
               
                   
               
               
                  1741 
                 atcatgagat ttttccatgt tgtgtacatc aatagttcat ctattttatt gctcagtaat 
               
               
                   
               
               
                  1801 
                 attccattgt gtggatgtat cactatttgt ttacacactc accactgata tataagttgc 
               
               
                   
               
               
                  1861 
                 ttccagtgtg aggctgtttt aaataaagct gctatgaata ttcatgtaag aaaaaaaaaa 
               
               
                   
               
               
                  1921 
                 aa 
               
               
                   
               
            
           
           
               
            
               
                 MAP3K7CL mRNA transcript 2269 bp 
               
               
                 SEQ ID NO: 15 
               
            
           
           
               
               
            
               
                     1 
                 cgcagccccg gttcctgccc gcacctctcc ctccacacct ccccgcaagc tgagggagcc 
               
               
                   
               
               
                    61 
                 ggctccggcc tcggccagcc caggaaggcg ctcccacagc gcagtggtgg gctgaagggc 
               
               
                   
               
               
                   121 
                 tcctcaagtg ccgccaaagt gggagcccag gcagaggagg cgccgagagc gagggagggc 
               
               
                   
               
               
                   181 
                 tgtgaggact gccagcacgc tgtcacctct caatagcagc ccaaacagat taagacacgg 
               
               
                   
               
               
                   241 
                 gaggtgaaag acaacttgag tggttaaatt actgtcatgc aaagcgacta gatggttcag 
               
               
                   
               
               
                   301 
                 ctgattgcac ctttagaagt tatgtggaac gaggcagcag atcttaagcc ccttgctctg 
               
               
                   
               
               
                   361 
                 tcacgcaggc tggaatgcag tggtggaatc atggctcact acagccctga cctcctgggc 
               
               
                   
               
               
                   421 
                 ccagagatgg agtctcgcta ttttgcccag gttggtcttg aacacctggc ttcaagcagt 
               
               
                   
               
               
                   481 
                 cctcctgctt ttggcttctt gaagtgcttg gattacagta tttcagtttt atgctctgca 
               
               
                   
               
               
                   541 
                 acaagtttgg ccatgttgga ggacaatcca aaggtcagca agttggctac tggcgattgg 
               
               
                   
               
               
                   601 
                 atgctcactc tgaagccaaa gtctattact gtgcccgtgg aaatccccag ctcccctctg 
               
               
                   
               
               
                   661 
                 gattgtcagt ggctgctatg cagcaggtgc agcctggtct ctcactgagt ctctactcca 
               
               
                   
               
               
                   721 
                 caaaggcaac gactggccaa ggcagtggct ggctctgggt tacacaagtg cagacactca 
               
               
                   
               
               
                   781 
                 actaagtgag ctggaagacc caggagaagg cggaggctca ggcgcccaca tgatcagcac 
               
               
                   
               
               
                   841 
                 agccagggta cctgctgaca agcctgtacg catcgccttt agcctcaatg acgcctcaga 
               
               
                   
               
               
                   901 
                 tgatacaccc cctgaagact ccattccttt ggtctttcca gaattagacc agcagctaca 
               
               
                   
               
               
                   961 
                 gcccctgccg ccttgtcatg actccgagga atccatggag gtgttcaaac agcactgcca 
               
               
                   
               
               
                  1021 
                 aatagcagaa gaataccatg aggtcaaaaa ggaaatcacc ctgcttgagc aaaggaagaa 
               
               
                   
               
               
                  1081 
                 ggagctcatt gccaagttag atcaggcaga aaaggagaag gtggatgctg ctgagctggt 
               
               
                   
               
               
                  1141 
                 tcgggaattc gaggctctga cggaggagaa tcggacgttg aggttggccc agtctcaatg 
               
               
                   
               
               
                  1201 
                 tgtggaacaa ctggagaaac ttcgaataca gtatcagaag aggcagggct cgtcctaact 
               
               
                   
               
               
                  1261 
                 ttaaattttt cagtgtgagc atacgaggct gatgactgcc ctgtgctggc caaaagattt 
               
               
                   
               
               
                  1321 
                 ttattttaaa tgaatagtga gtcagatcta ttgcttctct gtattaccca cacgacaact 
               
               
                   
               
               
                  1381 
                 gtctataatg agtttactgc ttgccagctt ctagcttgag agaagggata ttttaaatga 
               
               
                   
               
               
                  1441 
                 gatcattaac gtgaaactat tactagtata tgtttttgga gatcagaatt cttttccaaa 
               
               
                   
               
               
                  1501 
                 gatatatgtt tttttctttt ttaggaagat atgatcatgc tgtacaacag ggtagaaaat 
               
               
                   
               
               
                  1561 
                 gataaaaata gactattgac tgacccagct aagaatcgtg ggctgagcag agttaaacca 
               
               
                   
               
               
                  1621 
                 tgggacaaac ccataacatg ttcaccacag tttcacgtat gtgtattttt aaatttcatg 
               
               
                   
               
               
                  1681 
                 cctttaatat ttcaaatatg ctcaaattta aactgtcaga aacttctgtg catgtattta 
               
               
                   
               
               
                  1741 
                 tatttgccag agtataaact tttatactct gatttttatc cttcaatgat tgattatact 
               
               
                   
               
               
                  1801 
                 aagaataaat ggtcacatat cctaaaagct tcttcatgaa attattagca gaaaccatgt 
               
               
                   
               
               
                  1861 
                 ttgtaaccaa agcacatttg ccaatgctaa ctggctgttg taataataaa cagataaggc 
               
               
                   
               
               
                  1921 
                 tgcatttgct tcatgccatg tgacctcaca gtaaacatct ctgcctttgc ctgtgtgtgt 
               
               
                   
               
               
                  1981 
                 tctgggggag gggggacatg gaaaaatatt gtttggacat tacttgggtg agtgcccatg 
               
               
                   
               
               
                  2041 
                 aaaacatcag tgaacttgta actattgttt tgttttggat ttaaggagat gttttagatc 
               
               
                   
               
               
                  2101 
                 agtaacagct aataggaata tgcgagtaaa ttcagaattg aaacaatttc tccttgttct 
               
               
                   
               
               
                  2161 
                 acctatcacc acattttctc aaattgaact ctttgttata tgtccatttc tattcatgta 
               
               
                   
               
               
                  2221 
                 acttcttttt cattaaacat ggatcaaaac tgacaaaaaa aaaaaaaaa 
               
               
                   
               
            
           
           
               
            
               
                 MOB1B mRNA transcript 7091 bp 
               
               
                 SEQ ID NO: 16 
               
            
           
           
               
               
            
               
                     1 
                 gctacccact tccgccccct ccccctgcca ttggaactag ctgagccgaa ctagttgcgg 
               
               
                   
               
               
                    61 
                 ccaccgagca gccggctctc ggcacctcct cctccgcctc cctgtctcct gttccattcg 
               
               
                   
               
               
                   121 
                 cctttcccct tctttcccgg cccacgccgc tccgaggcct cgcgaccgcc gagcctgcag 
               
               
                   
               
               
                   181 
                 cctgccccgc ggccaacatg agcttcttgt tgagttctca gcctgaagtt gactggaact 
               
               
                   
               
               
                   241 
                 ttcagttaac aagtatttat cgaatacctg atctgtagtg ttggacttag acctatggaa 
               
               
                   
               
               
                   301 
                 ggagctactg atgtgaatga aagtggtagt cgctcttcta aaacttttaa accaaagaag 
               
               
                   
               
               
                   361 
                 aacattccag agggttctca ccagtatgag ctcttaaaac acgcagaagc cacacttggc 
               
               
                   
               
               
                   421 
                 agtggcaacc ttcggatggc tgtcatgctt cctgaagggg aagatctcaa tgaatgggtt 
               
               
                   
               
               
                   481 
                 gcagttaaca ctgtggattt cttcaatcag atcaacatgc tttatggaac tatcacagac 
               
               
                   
               
               
                   541 
                 ttctgtacag aagagagttg tccagtgatg tcagctggcc caaaatatga gtatcattgg 
               
               
                   
               
               
                   601 
                 gcagatggaa cgaacataaa gaaacctatt aagtgctctg caccaaagta tattgattac 
               
               
                   
               
               
                   661 
                 ttgatgactt gggttcagga ccagttggat gatgagacgt tatttccatc aaaaattggt 
               
               
                   
               
               
                   721 
                 gtcccgttcc caaagaattt catgtctgtg gcaaaaacta tactcaaacg cctctttagg 
               
               
                   
               
               
                   781 
                 gtttatgctc acatttatca tcagcatttt gaccctgtga tccagcttca ggaggaagca 
               
               
                   
               
               
                   841 
                 catctaaata catctttcaa gcactttatt ttttttgtcc aggaattcaa ccttattgat 
               
               
                   
               
               
                   901 
                 agaagagaac ttgcaccact ccaagaactg attgaaaaac tcacctcaaa agacagataa 
               
               
                   
               
               
                   961 
                 aaggatgcag agctgtgcaa attgttcctc aaatgaagca gtgtggagtg tattggggat 
               
               
                   
               
               
                  1021 
                 tttgttatat tttgttttta tctggattgt ttttgtccta ggtttggggg cgggggcttg 
               
               
                   
               
               
                  1081 
                 tttgggttcc tttttcttta ttccgattat gtgaaaccat attctattgc taggggaagc 
               
               
                   
               
               
                  1141 
                 caagaaccat tctctacaca cttgataagg gtaaatttac cttagtgttt ttaaacttgg 
               
               
                   
               
               
                  1201 
                 ttccggttac ctgaggagcc ttttaataat attgtgtgct gcaagaaagt gcctgttgat 
               
               
                   
               
               
                  1261 
                 tgaactgccg atggattggt ttctgtgtgg tataaattgt ggcccattta tgaagtcccc 
               
               
                   
               
               
                  1321 
                 aaaagagtta tgtttttaag tgccttggca ggctcacttc tgaggtgcaa aacatagata 
               
               
                   
               
               
                  1381 
                 tagaactgaa cagggcttga aacaatatta ggattactac ccagggcact tactggtgca 
               
               
                   
               
               
                  1441 
                 tgttgtaaca tatctatgat aaaagccata gtttacctaa aatggtgatt tccagccttt 
               
               
                   
               
               
                  1501 
                 actgctttga agaaacagaa tttgtaaagg tatgcatgta gaacataaaa aatatttctt 
               
               
                   
               
               
                  1561 
                 aattattttt tatattgatg gtaatatatt acgttcaaca atgcttaaag ctctacaagc 
               
               
                   
               
               
                  1621 
                 aggtcttttc ccacctcttg atatctgtga tactgaaact tgaggatgtt gaaatgtatt 
               
               
                   
               
               
                  1681 
                 acattttggc ctcctcctac atgttaactg cactgtagac gtaaaaactc aggttatata 
               
               
                   
               
               
                  1741 
                 taggattgcc atcttcagag gtgatgctga actgtgaggt tccctagtaa ttgccaaatg 
               
               
                   
               
               
                  1801 
                 agccgtaagt ctgcagaatt cccttccact ttgaagagaa ggggatagga atgtatattt 
               
               
                   
               
               
                  1861 
                 ggctgggggc atggagatgt tcgtatgtat gaggagttag ggatggggag tcaagttcta 
               
               
                   
               
               
                  1921 
                 gaaagttttg tctgaaaacc tttgaataga atggcatgaa gattttaatc aattacttat 
               
               
                   
               
               
                  1981 
                 aaacaaagtc ttagagactt ccttttagga atcaacttcc atgagaagtt aaaaataaat 
               
               
                   
               
               
                  2041 
                 tattaatttt aggtacagac attaaacatg gaatttaagg actgttgggg gaaattgatc 
               
               
                   
               
               
                  2101 
                 acttcttagc atttccattc agtgaatgga gctgatgttt gcctgtcatt ttaagatgat 
               
               
                   
               
               
                  2161 
                 accatacctt ctttggctat tataggtcca gtttgaagca ttctgacttc tggtttttcc 
               
               
                   
               
               
                  2221 
                 accctgaaag gaaatgcttt tctttgcagc agtattagat aatgaaaaat gctaattcag 
               
               
                   
               
               
                  2281 
                 tagttattaa cctctaaatt ttattcgcca tgactttcta gcgaattatt accataaata 
               
               
                   
               
               
                  2341 
                 acaatctcag aaacttagtt tttagaataa atattaattt ttccacttca gtcttatcct 
               
               
                   
               
               
                  2401 
                 agaaaatacc ctttttagaa atccagtttt agttttgtca ttttcgataa atctttcttc 
               
               
                   
               
               
                  2461 
                 agttagaaat atatatcctt ccttcagttg aaacatacac ctttttcaca tctaggaaga 
               
               
                   
               
               
                  2521 
                 aatgcttgct ctgaaatagt atagattaaa aacactcagt agaaaagaat ctaaaattaa 
               
               
                   
               
               
                  2581 
                 atgaatttgt tttgccatta aagtagagca gtgatacaat ttaatgccat tacaattatg 
               
               
                   
               
               
                  2641 
                 ttgactagaa actgcctttt tctccacttc atttctagca attatttacc aagtaccaac 
               
               
                   
               
               
                  2701 
                 agtagaagta acaggaaagc ctggcagagt taaatatctt ggacatttat tggtaaagct 
               
               
                   
               
               
                  2761 
                 tatttataaa ctgcagccag agctagttaa tttccttaaa tctttttgta ttcagataga 
               
               
                   
               
               
                  2821 
                 taatatgaat cattatgggt tgattcagaa ataaaatttg tgaggtgatt ttgaatcttg 
               
               
                   
               
               
                  2881 
                 tccatatagg aaaatgaagc acagaattac tcagtcttcc atattgtatt tgacttcata 
               
               
                   
               
               
                  2941 
                 tcaatctagt aaaaaaggag ttgcaatagc caagtataga gagaacagtg aaaaattaat 
               
               
                   
               
               
                  3001 
                 cttgcccttt caagccttat acagtagtac actgtacttg tttttagtag taagacctac 
               
               
                   
               
               
                  3061 
                 tttcccacta tatgtagata gtttgttttc actgtgccag aatctcaggt gcctgcttag 
               
               
                   
               
               
                  3121 
                 agtatttctt taatcacagt cactgggaag taaggagatg tatatatgtg tatatatggt 
               
               
                   
               
               
                  3181 
                 aacaaagcat agcagttctc taggggagag gcctggcatt gcacatggtg ttacatggct 
               
               
                   
               
               
                  3241 
                 acaagtaagg aaaaaatcag aaagtgaaag aactgatgta ataaaaggtt gatttggttg 
               
               
                   
               
               
                  3301 
                 gttcccatga aagttagtaa gatgcccttt taaatataag gatcagtgct ttgttctgca 
               
               
                   
               
               
                  3361 
                 gcagagtttg ctgataaatg tctgttggat tctttttgga tttctttaat taatttgtaa 
               
               
                   
               
               
                  3421 
                 gtaaccaaga taattatttt cccccttgcc ctctatatta atacgtagct ataaagcaac 
               
               
                   
               
               
                  3481 
                 agttggtttt cttatccttt gataaaagca tcccataaaa tataaagtag taagttaaca 
               
               
                   
               
               
                  3541 
                 tagtattatt gtcacacaca atgctttttt tggttaaatg ttgatacgaa gcaatgtttt 
               
               
                   
               
               
                  3601 
                 ggaattactt taattgatgg agtagtggtg gtagagagaa attaataaca aaaagagtga 
               
               
                   
               
               
                  3661 
                 aaatatttta attagcagta gatggtgcta ccggctttca tttgctgact tgattattcc 
               
               
                   
               
               
                  3721 
                 ctttctctta aaaaccatgg cattagactg cactaaatta acaagcatgt tagttgctgg 
               
               
                   
               
               
                  3781 
                 tagaggtttt ggaggttaat ttacctcaaa ttggaagact tttaattgca gtctctttct 
               
               
                   
               
               
                  3841 
                 accttccctc tgttagtcat ttgtaaattc taaatggtca ccataaaatg tattaggtag 
               
               
                   
               
               
                  3901 
                 gagaagatac gttttacgta taatatatct cagactgagt tactgcctgt cttatcagga 
               
               
                   
               
               
                  3961 
                 tggataaaac actacagtct cttatcagga aatagagatg atgtggatat ttatatatta 
               
               
                   
               
               
                  4021 
                 catatataac caccagactc cattttacat attagcattt tccttgctta tgggaaaata 
               
               
                   
               
               
                  4081 
                 gcaaaacaac atttcattta tacttttgtt tacccctctc tgagacaggt tttgataacc 
               
               
                   
               
               
                  4141 
                 actgaaatgg tagaatatgt gagatacaaa tattgagttg tagaactttc tttttaaggt 
               
               
                   
               
               
                  4201 
                 gaataagtca tgccttaaca tccaaataag agttcatctt cagagtggtt cttttgggag 
               
               
                   
               
               
                  4261 
                 cactgtttat tccagctata ccgcaaaagt acaacgtttt tggaactgtt ctagagcata 
               
               
                   
               
               
                  4321 
                 ccatgaaaag cagtttgtta ttatgcagga aaatcagttt catcatttta gttacactaa 
               
               
                   
               
               
                  4381 
                 acacttttgg cagcttaata tgaccttttt aaattttttt tatttttttt atttttattt 
               
               
                   
               
               
                  4441 
                 ctttaagatg gagtcttgct ctgttgcccg ggctggagta caatggcatg atctcagctc 
               
               
                   
               
               
                  4501 
                 actgcaacct ccacctcctg ggttcaagca tttctcctgc ctcagcctcc caagtagctg 
               
               
                   
               
               
                  4561 
                 ggattacagg cagcaccaca cctggctaat tttcatattt ttagtagaga tggggtttca 
               
               
                   
               
               
                  4621 
                 acatattggc caggctggtc tcaaactcct gacctcaagt gatccgccct ccccagcctc 
               
               
                   
               
               
                  4681 
                 ccaaagtgct gggattacag gtgtgagcca ccacagccag ccagtatgac ctatcttaat 
               
               
                   
               
               
                  4741 
                 catcagctca actgtaattt aaatttggct gttctctgga gctaaaccat tagggaagtt 
               
               
                   
               
               
                  4801 
                 caaaggaatg tgccatgatt tccgaatttg cacaagagaa tgttttaagc attggtagca 
               
               
                   
               
               
                  4861 
                 taattgaata aaagaatagt ttcctgatgt cactattttg aagtggaaat tatcacttgg 
               
               
                   
               
               
                  4921 
                 atgtggaggt tttacttttt aaaaacactc agcttaatta ccttacccta attacctcag 
               
               
                   
               
               
                  4981 
                 ttagatatac taatggaaaa aaaccaagtc ctttctctag aacttgtttt ctatttttgt 
               
               
                   
               
               
                  5041 
                 tccttttcat gaaaacttct caatttaatt ttaactactg taggatagta ttgattgaat 
               
               
                   
               
               
                  5101 
                 ggatactatg gaaaagtgga tccaatattt aagatagaag tagtttaagg agacaacagc 
               
               
                   
               
               
                  5161 
                 ctttactgcc attttttttt aaatgttttc actcagatga acaatttgac tttaataaaa 
               
               
                   
               
               
                  5221 
                 gactggagat ttttgtacaa agaaatagga ataagtttca tatactaatt atgctgagtt 
               
               
                   
               
               
                  5281 
                 ttaagcccac atatcacaaa atatttagaa ttgtataacc ttttcatata tttataactt 
               
               
                   
               
               
                  5341 
                 ttaatgtctt tttaaaagat gtgggaccaa aaatatattt ataatttgga aatgtgactg 
               
               
                   
               
               
                  5401 
                 cataccaata agaaaactta ccttattttg aaatttatct gggatattaa agaatctacc 
               
               
                   
               
               
                  5461 
                 aattcttaaa aacacagatt tatacttcaa gcttattcta aaattaaaga atatatacca 
               
               
                   
               
               
                  5521 
                 attcttagaa acactttaag gactactctt aaataactta aatatcagag ttttgttgta 
               
               
                   
               
               
                  5581 
                 atattaaaat ttaccgtgga aatcactgtt gttcagctat caccttaatt gtgtatgata 
               
               
                   
               
               
                  5641 
                 tgataaatgt ttagcagtaa agctatctta agatttaatg gaaaagttta atttgaagat 
               
               
                   
               
               
                  5701 
                 gtaacaaaaa ttctgaccac agttgattct gaatttttaa ggctttccta ataggctgat 
               
               
                   
               
               
                  5761 
                 cacagagaat aatccatttt gaaggtataa aactgcactg tatgtctgtc acttgtagct 
               
               
                   
               
               
                  5821 
                 gaactgattc acattttgac aaaagagaga aaatacaaaa atgagttttg caaatgtaat 
               
               
                   
               
               
                  5881 
                 aactttttct gcatatagaa ctaaataatt gaaaaatatg ggctatagtt ctcaaaggta 
               
               
                   
               
               
                  5941 
                 gatagtaaaa tcactggctt tttccagctg tatgtttttc cactgtgcgt gtacacacac 
               
               
                   
               
               
                  6001 
                 actggaaaat aattaggctg attttgcagg tcttcatcgt tagagattct gaagtattta 
               
               
                   
               
               
                  6061 
                 ctgtcaattc ataggtttca gtttattcag gaaattagtg ttcgacagct ttttttaaat 
               
               
                   
               
               
                  6121 
                 tatttcactg aagctgagat tattagtgat acaaagttaa aatttcaata tttaatttct 
               
               
                   
               
               
                  6181 
                 ctatatatta ttaatattaa attgtttttt acttataaat tcatgttctc atctgattta 
               
               
                   
               
               
                  6241 
                 atattaaatt tgtataggtg ggcgtttctt accattttgc acaagttttt gtttttctga 
               
               
                   
               
               
                  6301 
                 aatacttaat tgtgcaggtt gtaaaaaaga ttagtgcatt ttcattttaa ggatgctttg 
               
               
                   
               
               
                  6361 
                 ctccttaaat tgttcgacag aaatgacttt ttagggaaag tagttttttt ggagctacta 
               
               
                   
               
               
                  6421 
                 acttgtattt atcattgtac atgcataacc agggtggtga gggcaccaat cttgtaggaa 
               
               
                   
               
               
                  6481 
                 acacttactt gatgttttat ttgaactttt cctataggtt taacttttac tgcatagaat 
               
               
                   
               
               
                  6541 
                 taacactagg aacagtgtca tgaaatctgg gttgaaggag aatacagtat atatgagaac 
               
               
                   
               
               
                  6601 
                 acttaaagtt caaacagaaa tcatttccga agacaaaagc agaggaatat tgtcagtgcc 
               
               
                   
               
               
                  6661 
                 aagtaatgga agaataaggg cggcatttac actgtgcaag tattgagaag agtgcataaa 
               
               
                   
               
               
                  6721 
                 gacagggaac tactctcatg gagacagttt ctctcttata atcaagtaac tagaagggga 
               
               
                   
               
               
                  6781 
                 aaaatcatct aagttatgaa atccaacata ggcgctatat tacaaactgt gccggattat 
               
               
                   
               
               
                  6841 
                 gcaaattgta gttgttactg atcaaagttt aattgcttca tttttgttta aaaagggata 
               
               
                   
               
               
                  6901 
                 ctgatgtcag aaaatctgta atatgtttta ttcaaaagat gtaaataatg tatacagact 
               
               
                   
               
               
                  6961 
                 tgtatgtgat gggatgggaa atatttaaat tctaggtgtt tttttttttt taaagaagaa 
               
               
                   
               
               
                  7021 
                 actcaatgtt tataagaaaa aaatgaataa atagttacgt ttggccatga atcctgaaaa 
               
               
                   
               
               
                  7081 
                 aaaaaaaaaa a 
               
               
                   
               
            
           
           
               
            
               
                 RAB27B mRNA transcript 7003 bp 
               
               
                 SEQ ID NO: 17 
               
            
           
           
               
               
            
               
                     1 
                 actcgcagtc ctgacgggca ggggctgcgg accgcccggc cttggaccca tccggagcca 
               
               
                   
               
               
                    61 
                 caggttggag gagataagta gctgtccccg tgctcatcgc cctgtggagc agatcctgtc 
               
               
                   
               
               
                   121 
                 tccttgccga cggtggagcc cgggagttcc agggcttggg aaggggaagg aaacctctct 
               
               
                   
               
               
                   181 
                 gaaatctgac acctgctctc ccggcaagga aacttcgcag gctgaccgac caagaccatc 
               
               
                   
               
               
                   241 
                 actatgaccg atggagacta tgattatctg atcaaactcc tggccctcgg ggattcaggg 
               
               
                   
               
               
                   301 
                 gtggggaaga caacatttct ttatagatac acagataata aattcaatcc caaattcatc 
               
               
                   
               
               
                   361 
                 actacagcag gaatagactt tcgggaaaaa cgtgtggttt ataatgcaca aggaccgaat 
               
               
                   
               
               
                   421 
                 ggatcttcag ggaaagcatt taaagtgcat cttcagcttt gggacactgc gggacaagag 
               
               
                   
               
               
                   481 
                 cggttccgga gtctcaccac tgcatttttc agagacgcca tgggcttctt attaatgttt 
               
               
                   
               
               
                   541 
                 gacctcacca gtcaacagag cttcttaaat gtcagaaact ggatgagcca actgcaagca 
               
               
                   
               
               
                   601 
                 aatgcttatt gtgaaaatcc agatatagta ttaattggca acaaggcaga cctaccagat 
               
               
                   
               
               
                   661 
                 cagagggaag tcaatgaacg gcaagctcgg gaactggctg acaaatatgg cataccatat 
               
               
                   
               
               
                   721 
                 tttgaaacaa gtgcagcaac tggacagaat gtggagaaag ctgtagaaac ccttttggac 
               
               
                   
               
               
                   781 
                 ttaatcatga agcgaatgga acagtgtgtg gagaagacac aaatccctga tactgtcaat 
               
               
                   
               
               
                   841 
                 ggtggaaatt ctggaaactt ggatggggaa aagccaccag agaagaaatg tatctgctag 
               
               
                   
               
               
                   901 
                 actctacata gaaactgaac atcaagaacc ccaccaaaat attactttta aaaacaatga 
               
               
                   
               
               
                   961 
                 caaaccacac aattgttgtt gagtaaacca cgcacaatgg catgtctttc tttttctgcc 
               
               
                   
               
               
                  1021 
                 agaaaatcta ttttaagaaa ccagaatagt caacagtgtt caaaagaatt gactagttat 
               
               
                   
               
               
                  1081 
                 ccctgaggcc ctttcaaaca tgatcaaaga tttcccaatg tgatctcatc atcatggata 
               
               
                   
               
               
                  1141 
                 ctcaatttgt tttttcttat agagaaaatg agtatataag acaatataca agaagaaata 
               
               
                   
               
               
                  1201 
                 tcagtgagtt ttaaatcaga acaagttacc tgtcacattg aagaaaaggg taggcactaa 
               
               
                   
               
               
                  1261 
                 agggagaaca cagaaagaag aatttctaaa atattggatt tacttcttat attgagtcag 
               
               
                   
               
               
                  1321 
                 atgcatactt ttagatttgc attggggaaa atgtactagc taaaaatgga tacacaatga 
               
               
                   
               
               
                  1381 
                 agaattctat ttggctaatt aagaatgata tactatgtac acccaataag ctgtactaga 
               
               
                   
               
               
                  1441 
                 atgaataaat tactgataag gttacaaata ggtaaatgtc acacttctgt taaaatgcag 
               
               
                   
               
               
                  1501 
                 gaggtagtgt cataatgccg tctttatatt cttaataaat agcactttga caagaacagg 
               
               
                   
               
               
                  1561 
                 actgtaaatg atgaagtaca agacaaatac cctgggaaaa aaaatgaaag tatgagaaat 
               
               
                   
               
               
                  1621 
                 tggcattcct acagctgaaa ttcaatgcat ctgttagaga tgtctggaag ggttactcag 
               
               
                   
               
               
                  1681 
                 ccaaatttta ctcaagccaa ttaggagctg atattatcag ttggaattaa gagaactcca 
               
               
                   
               
               
                  1741 
                 gaggtttcca tttcaaacaa aattttagaa attggtttgg tgttcagctt cacatttcat 
               
               
                   
               
               
                  1801 
                 tttttcttag cacatgttga taaaatagtc acaaggagaa attaccagtt acggtttatt 
               
               
                   
               
               
                  1861 
                 aaatctcttt taaaatgcag tcaaggaaaa ctagccttga atttttttta gataaaataa 
               
               
                   
               
               
                  1921 
                 gatggtgata tgaaacaaaa agtggcaatt attgcaggtt tccttttagt ttacaaaagt 
               
               
                   
               
               
                  1981 
                 actggaaact aaatcatatt tcttccctcc aaatttcacc cattcctgac tttgaatcaa 
               
               
                   
               
               
                  2041 
                 ttgcagaaat gcaggtgtgt tactttgttg atcaataact ttggaacaat tatggatcaa 
               
               
                   
               
               
                  2101 
                 ttctatggtc actctgaatt ttcatgtcat taatcacata aaaattgata atacctcatt 
               
               
                   
               
               
                  2161 
                 ctgtattaca atatgatttt attttgccaa aggcaagaca cctatagttg agctgtattt 
               
               
                   
               
               
                  2221 
                 tgggggactg ggtgaggaag gacttctgat cttatctcaa caaaaaactg gccagtattt 
               
               
                   
               
               
                  2281 
                 ttgttaatgt aaagcttcct tttctttcta aaaaatagta acaaaattat ttttcattgg 
               
               
                   
               
               
                  2341 
                 cctattctgt tcttgtgtct aaactaacat tacattaatt tttaatctta gtttctgata 
               
               
                   
               
               
                  2401 
                 aacacaagcc attcctatca aaatattatt tatttcagtc aattttacca aataacaaag 
               
               
                   
               
               
                  2461 
                 acaatatatt ttcgtttttt tttattatga gcatatgatt ttttgacagg ctgtttcctc 
               
               
                   
               
               
                  2521 
                 gtcgtataga ttttttccaa tcaaacctac tttttccata ctctgtgcat attttttgtg 
               
               
                   
               
               
                  2581 
                 aagttataca cattgaagac cctaaaaatc ccagtccatc attcagctta cctctgcgaa 
               
               
                   
               
               
                  2641 
                 cttctatctg gtattgaatc agtttcagaa acacagacag atccaaggaa atgtctcttt 
               
               
                   
               
               
                  2701 
                 ataatgttct taggatggac tagacccata aatgtgccat gaatcaaaat attaataatt 
               
               
                   
               
               
                  2761 
                 tgaaagcttt catgctgtta gcccctgatg aaattctcag cattaactgg ccagctcctc 
               
               
                   
               
               
                  2821 
                 tgatttctgc agcatcgcaa caggttcgaa gatgggttgt ggctgggtat tccctcccat 
               
               
                   
               
               
                  2881 
                 ggtgtttcct ctgggatgct cttcattatc tcaatgcctg tgccatgaag atagaaaact 
               
               
                   
               
               
                  2941 
                 gtaagctaac atttaagatg tttcttctgg aaggaaagtg agcaggaaca agttatattg 
               
               
                   
               
               
                  3001 
                 ccactgctgt ggcaaatttt ggtgaacttt tggggtcatt atatcaattt tttctttgga 
               
               
                   
               
               
                  3061 
                 ttcaaattgt aatgtcccct gcatttcctt aatagggaat gtgaaacctt tataaaactc 
               
               
                   
               
               
                  3121 
                 taaaagtatt ctgttttgat atgtcttttt gtttctattc attttcagtt atatgattga 
               
               
                   
               
               
                  3181 
                 tttacttatg ccaagattct gtcactgtca gttatttaat gagtgttttt tcagggtctg 
               
               
                   
               
               
                  3241 
                 ttttaagatc attatttgat agctgtagca tgaagcagag gttgatgatg cccataattg 
               
               
                   
               
               
                  3301 
                 caagactatt cctgtaaaaa taacaattat tgggtaataa cttcaagagg aatgagaagt 
               
               
                   
               
               
                  3361 
                 gacaaaattg atttaaaata ttgttctact tataaataaa tgcttgatat aaaaaatttt 
               
               
                   
               
               
                  3421 
                 ctccataaag tttgacatct gaccccagat tctatgtaat cattattaga aattccttct 
               
               
                   
               
               
                  3481 
                 ctcattattt caggattagt agttctgtgt aattcatttt acaatttcaa attgttctgg 
               
               
                   
               
               
                  3541 
                 tgccataaag tatacagact actttaaaga tttccaaatc ccctaattta ccccacaaca 
               
               
                   
               
               
                  3601 
                 gcatgtaatt ttagccaaga tatgtcctgt tactaagtat ctcccaatgc tttagtaaaa 
               
               
                   
               
               
                  3661 
                 cgtatttagg agaaatgttg aaaatgtaca tgaagctcct ttctgatata gaaaccattt 
               
               
                   
               
               
                  3721 
                 ctggagtatt tacactggtt tgatgtttac attgctctaa ctcggtgcct cagatacctc 
               
               
                   
               
               
                  3781 
                 tgtgaccaaa tttgtctcca accacatagc tcatttccta taatgttata tcataggaag 
               
               
                   
               
               
                  3841 
                 ccctcacaga gacactaaca cagctaaaga tcttctgata ttatcagcaa gggatgcaag 
               
               
                   
               
               
                  3901 
                 gactttattg gaatctggag agtttaactg ccttctcttg gtctcctcac ttacttctta 
               
               
                   
               
               
                  3961 
                 tgaagttggc attacctgag actcttagct gtgattaggt acaagcttac cttttagggt 
               
               
                   
               
               
                  4021 
                 agaaaaagaa agatcatttg aaaaatgtat ctaaaataat ccagagaaca taatgtttgt 
               
               
                   
               
               
                  4081 
                 cttggtctga taatgataag aagtcaagga ttggcagaga aaatactaaa cgccaagagt 
               
               
                   
               
               
                  4141 
                 tgagcctgtg ggtctctcca taagagtttt aaaactcttg ccagttacca ctttatccaa 
               
               
                   
               
               
                  4201 
                 tttgctatca ttttcgtatt atcagctatc gccctgtaaa atattcaaaa ctagctattt 
               
               
                   
               
               
                  4261 
                 ctaaagtaaa cattttatct gttactttta accagatagg tgtctttgtc atccttctac 
               
               
                   
               
               
                  4321 
                 tataaattgt tctttgccaa cctgtacagg tagatgaacc aggcgagagt tttaatcagc 
               
               
                   
               
               
                  4381 
                 cttttcttgt cccctttgta agaaagagat gcttgccata gagaaggaca tgagtacatt 
               
               
                   
               
               
                  4441 
                 aaaaataatt taatagccac aatatgatgt tctttaagct gcaaattgag tacactggga 
               
               
                   
               
               
                  4501 
                 atcaacaaat ttgatgaagc ctgtctgtct cttcaccagt ggagtgagtg cagcagttag 
               
               
                   
               
               
                  4561 
                 aaagagaagc aatattgtgc aactggtgca gcggtgagtt aatcatagtg tataaccttg 
               
               
                   
               
               
                  4621 
                 tgttcatgaa acaggttgtt cattgttctg catctctctt catttaaaaa ggatacacaa 
               
               
                   
               
               
                  4681 
                 ttctttcctc attgcatatt acaccaaacg tttgagggaa aaatcctcat tcgtaaagga 
               
               
                   
               
               
                  4741 
                 ttttggatgt ataatctaaa actcaacaat aaagaaataa tattccaagt ctctggtttc 
               
               
                   
               
               
                  4801 
                 ctaagataca taataactgt ttataaagaa ggtctaagag ctgatatttg ccaaagtgat 
               
               
                   
               
               
                  4861 
                 agaagagttg ttttttcctc tctactacca agctttaaga cattaaaaga agtctagtgt 
               
               
                   
               
               
                  4921 
                 atttgaatat tttagagaaa gctttatcat tttttaagat gccaagatgc tgcctacgtt 
               
               
                   
               
               
                  4981 
                 tgcaaaagtt gtctaagaat tcaccatgag ctatattttc ttctggatct ttgaccaagg 
               
               
                   
               
               
                  5041 
                 tgatgtcagc ttatttctgg ggaaggtgtt gagctcttat acatgaaaat ggatataggc 
               
               
                   
               
               
                  5101 
                 tattctctgg gatgagtgtc atttcaatgc tttataaatc catgaagctg cttgtctcat 
               
               
                   
               
               
                  5161 
                 aaagtagaac tgatacaaat tttggttgga tatatagaga attttacaaa tgtattgcct 
               
               
                   
               
               
                  5221 
                 tagaatttct gggtggagac ccaactacaa tgacattgtc atgccagaac tataaagata 
               
               
                   
               
               
                  5281 
                 attagagtta aaagttgttt aaattgtgcc cttaaataca gcagaacctg gagaaggtca 
               
               
                   
               
               
                  5341 
                 tacttcaaag gtcgattttg agtccgaaca aagaaagacc tagtaacaga tagttttttt 
               
               
                   
               
               
                  5401 
                 ttgttcattt tcttctacca agtagaggtt tatgccctca gaactaaact agtaaaaata 
               
               
                   
               
               
                  5461 
                 tctgaacaaa aaacctttcg ttgttggcat aaaaatgtga tacacttaga gacattttgt 
               
               
                   
               
               
                  5521 
                 ttattgcata taaatctaat ttttccataa attagattta tgatattttc ataaagcact 
               
               
                   
               
               
                  5581 
                 tgattagttt ttcaaggcgt accatcacaa agatgctttc ctgcagagtt ctttgtatca 
               
               
                   
               
               
                  5641 
                 acagcctatg gttgagatgt tttctcattt cctgtagaga gagaatacca ctaacaaaca 
               
               
                   
               
               
                  5701 
                 aacaaaaact ttagtgccaa aatagtggaa ctattttgtc atctttcgag aaaaaaatat 
               
               
                   
               
               
                  5761 
                 acaaagaagt catcttttca ttaagtggat tccctggttc ctttccagct ggttgtggaa 
               
               
                   
               
               
                  5821 
                 gtaatggcta acatccttca gctgactttg tctacaagga ttattagcaa attctgtagg 
               
               
                   
               
               
                  5881 
                 agcaagcatg tccgacctta acttaatgga tcccttattc aatcagtggc ttctgtcttt 
               
               
                   
               
               
                  5941 
                 atgtctgttg gcatatcaaa atggtttctg ttcctagaaa agtaataaca tatgcttatc 
               
               
                   
               
               
                  6001 
                 tttattcttt ttccaggtga ttttgttttc aaatgctcct tgtgaaaaca cctagtgttg 
               
               
                   
               
               
                  6061 
                 tagaaaggaa agtggccaga aagaacaact tgggaccatg agtaggtcat taaatagctt 
               
               
                   
               
               
                  6121 
                 agtgatttat cctcatatag ggcttataaa ccctgtatgt gtttatatgt gcttcacaga 
               
               
                   
               
               
                  6181 
                 gttcgtgtca ggctcaaagg agatatgtat aagaaagtgg tttgtaaatt atgttccatt 
               
               
                   
               
               
                  6241 
                 tcataaatag acactattca caaactaaaa tctaataaaa aaccacagtt gtaatttaaa 
               
               
                   
               
               
                  6301 
                 ctgcttgata taaaaagagg tatcatagca gggaaaacac actaattttc atacagtaga 
               
               
                   
               
               
                  6361 
                 ggtattgaaa actgaaaatg ggaaggcaac ttgaagtcat tgtatttgat tgaaaatgtt 
               
               
                   
               
               
                  6421 
                 taatacatct cattattgac aaaatatgtc atcttgtatt tatttcaagg aaaccaatga 
               
               
                   
               
               
                  6481 
                 attctaggta gtatattaca agttggtcaa aatattccat gtacaaatag ggcttctgtg 
               
               
                   
               
               
                  6541 
                 tccatagcct tgtaagagat actgattgta tctgaaatta ttttttaaaa aaataaatta 
               
               
                   
               
               
                  6601 
                 tcctgcttta gttagtgtgt taaaagtaga cgatgttcta atataacact gaagtgcttc 
               
               
                   
               
               
                  6661 
                 attgtatccc aacagtttac cttcaagtaa tattatcttt atttttaggc taagcacgtt 
               
               
                   
               
               
                  6721 
                 tgattatttt gtctgtctcc tatatagatc tgttttgtct agtgctatga atgtaactta 
               
               
                   
               
               
                  6781 
                 aaactataaa cttgaagttt ttattctata tgccccttaa tagactgtgg ttcctgacgc 
               
               
                   
               
               
                  6841 
                 acactgttag gtcattattt tgttgtacca aagttctagt ggcttcagaa atcatagcat 
               
               
                   
               
               
                  6901 
                 ccaatgattt tttggtgtct ggctatgaat actatggttg agaattgtat tcagtgattg 
               
               
                   
               
               
                  6961 
                 tttctgcaca cttttcaaat aaaaaatgaa tttttatcaa tta 
               
               
                   
               
            
           
           
               
            
               
                 RGS18 mRNA transcript 2158 bp 
               
               
                 SEQ ID NO: 18 
               
            
           
           
               
               
            
               
                     1 
                 agttctgcat ttctgcagag acagaaagaa acgcagctct tgacttcttt tttgtaaaca 
               
               
                   
               
               
                    61 
                 ttactgtaag agttgtgata actttttatt ctactatgta tatgtatgga atagtattaa 
               
               
                   
               
               
                   121 
                 taaatgaact agggaaggat gtaataaatt agacatctct tcattttaga gagaagatgg 
               
               
                   
               
               
                   181 
                 aaacaacatt gcttttcttt tctcaaataa atatgtgtga atcaaaagaa aaaacttttt 
               
               
                   
               
               
                   241 
                 tcaagttaat acatggttca ggaaaagaag aaacaagcaa agaagccaaa atcagagcta 
               
               
                   
               
               
                   301 
                 aggaaaaaag aaatagacta agtcttcttg tgcagaaacc tgagtttcat gaagacaccc 
               
               
                   
               
               
                   361 
                 gctccagtag atctgggcac ttggccaaag aaacaagagt ctcccctgaa gaggcagtga 
               
               
                   
               
               
                   421 
                 aatggggtga atcatttgac aaactgcttt cccatagaga tggactagag gcttttacca 
               
               
                   
               
               
                   481 
                 gatttcttaa aactgaattc agtgaagaaa atattgaatt ttggatagcc tgtgaagatt 
               
               
                   
               
               
                   541 
                 tcaagaaaag caagggacct caacaaattc accttaaagc aaaagcaata tatgagaaat 
               
               
                   
               
               
                   601 
                 ttatacagac tgatgcccca aaagaggtta accttgattt tcacacaaaa gaagtcatta 
               
               
                   
               
               
                   661 
                 caaacagcat cactcaacct accctccaca gttttgatgc tgcacaaagc agagtgtatc 
               
               
                   
               
               
                   721 
                 agctcatgga acaagacagt tatacacgtt ttctgaaatc tgacatctat ttagacttga 
               
               
                   
               
               
                   781 
                 tggaaggaag acctcagaga ccaacaaatc ttaggagacg atcacgctca tttacctgca 
               
               
                   
               
               
                   841 
                 atgaattcca agatgtacaa tcagatgttg ccatttggtt ataaagaaaa ttgattttgc 
               
               
                   
               
               
                   901 
                 tcatttttat gacaaactta tacatctgct tctaacatat cgcatgttta tgttaagatt 
               
               
                   
               
               
                   961 
                 tggtcccatc ctttaaactg aaatatgtca tgtgaaatta ttttaaaaat gtaaaaacaa 
               
               
                   
               
               
                  1021 
                 aactttctgc taacaaaata catacagtat ctgccagtat attctgtaaa accttctatt 
               
               
                   
               
               
                  1081 
                 tgatgtcatt ccatttataa tcagaaaaaa aacttatttc ttaatcaaaa ggcagtacaa 
               
               
                   
               
               
                  1141 
                 aaaaagtaat aatgttttat aagattgtag agttaagtaa aagttaagct tttgcaaagt 
               
               
                   
               
               
                  1201 
                 tgtcaaaagt tcaaacaaaa gtctagttgg gattttttac caaagcagca taatatgtgt 
               
               
                   
               
               
                  1261 
                 tatataaaca taataatact cagatatcca aatgttcaga tagcattttt cataatgaa” 
               
               
                   
               
               
                  1321 
                 gttctctttt ttttggtaat agtgtagaag tgatctggtt cttacaatgg gagatgaaga 
               
               
                   
               
               
                  1381 
                 acatttatta ttgggttact actaaccctg tcccaagaat agtaatatca cctctagtta 
               
               
                   
               
               
                  1441 
                 taagccagca acaggaactt ttgtgaagac acattcatct ctacagaact tcagattaaa 
               
               
                   
               
               
                  1501 
                 tataatctag attaatgact gagaataaga tccacatttg aactcattcc taagtgaaca 
               
               
                   
               
               
                  1561 
                 tggacgtacc cagttataca aagtacttct gttggtcaca gaaacatgac cagattttgc 
               
               
                   
               
               
                  1621 
                 atatctccag gtagggaact aagtagacta ccttatcacc ggctaagaaa acttgctact 
               
               
                   
               
               
                  1681 
                 aaactattag gccatcaatg gcttgaataa aaaccagaga aggtttttcc caggacgtct 
               
               
                   
               
               
                  1741 
                 catgtttggc cctttagaat tggggtagaa atcagaaatg agatgagggg aagaagcaag 
               
               
                   
               
               
                  1801 
                 gagtctaagg ccctagcgat ttgggcatct gccacattgg ttcatattca gaaagtgtta 
               
               
                   
               
               
                  1861 
                 tctcattgat tatattcttg ttaagcaaat ctccttaagt aattattatt caaataagat 
               
               
                   
               
               
                  1921 
                 tatactcata catctatatg tcactgtttt aaagagatat ttaattttta atgtgtgtta 
               
               
                   
               
               
                  1981 
                 catggtctgt aaatacttgt atttaaaaat gccatgcatt aggctttgga aatttaatgt 
               
               
                   
               
               
                  2041 
                 tagttgaaat gtaaaatgtg aaaactttag atcatttgta gtaataaata tttttaactt 
               
               
                   
               
               
                  2101 
                 cattcataca gttaagttta tctgacaata aaagctctga ctgaaaaaaa aaaaaaaa 
               
               
                   
               
            
           
           
               
            
               
                 TBC1D15 mRNA transcript 5852 bp  
               
               
                 SEQ ID NO: 19 
               
            
           
           
               
               
            
               
                     1 
                 ttttgccgga tgttgttgta tgtccgagag acacgtgagg ttctgctacg tcattaccag 
               
               
                   
               
               
                    61 
                 gcacgcgcag gaaacatggc ggcggcgggt gttgtgagcg ggaaggtttt tggtttcttc 
               
               
                   
               
               
                   121 
                 ttgattcaat cttgataagt agtatgtgtc caggacttta tccatactcc agtttgttgg 
               
               
                   
               
               
                   181 
                 agtatggtag gagtatgatt atatatgaac aagaaggagt atatattcac tcatcttgtg 
               
               
                   
               
               
                   241 
                 gaaagaccaa tgaccaagac ggcttgattt caggaatatt acgtgtttta gaaaaggatg 
               
               
                   
               
               
                   301 
                 ccgaagtaat agtggactgg agaccattgg atgatgcatt agattcctct agtattctct 
               
               
                   
               
               
                   361 
                 atgctagaaa ggactccagt tcagttgtag aatggactca ggccccaaaa gaaagaggtc 
               
               
                   
               
               
                   421 
                 atcgaggatc agaacatctg aacagttacg aagcagaatg ggacatggtt aatacagttt 
               
               
                   
               
               
                   481 
                 catttaaaag gaaaccacat accaatggag atgctccaag tcatagaaat gggaaaagca 
               
               
                   
               
               
                   541 
                 aatggtcatt cctgttcagt ttgacagacc tgaaatcaat caagcaaaac aaagagggta 
               
               
                   
               
               
                   601 
                 tgggctggtc ctatttggta ttctgtctaa aggatgacgt cgttctccct gctctacact 
               
               
                   
               
               
                   661 
                 ttcatcaagg agatagcaaa ctactgattg aatctcttga aaaatatgtg gtattgtgtg 
               
               
                   
               
               
                   721 
                 aatctccaca ggataaaaga acacttcttg tgaattgtca gaataagagt ctttcacagt 
               
               
                   
               
               
                   781 
                 cttttgaaaa tcttcctgat gagccagcat atggtttaat acaaaaaatt aaaaaggacc 
               
               
                   
               
               
                   841 
                 cttatacggc aactatgata ggattttcca aagtcacaaa ctacattttt gacagtttga 
               
               
                   
               
               
                   901 
                 gaggcagcga tccctctaca catcaacgac caccttcaga aatggcagat tttcttagtg 
               
               
                   
               
               
                   961 
                 atgctattcc aggtctaaag ataaatcaac aagaagaacc aggatttgaa gtcatcacaa 
               
               
                   
               
               
                  1021 
                 gaattgattt gggggaacgc cctgttgttc aaaggagaga accggtatca ctggaagaat 
               
               
                   
               
               
                  1081 
                 ggactaagaa cattgattct gaaggaagaa ttttaaatgt agataatatg aagcagatga 
               
               
                   
               
               
                  1141 
                 tatttagagg gggacttagt catgcattga gaaagcaagc atggaaattt cttctgggtt 
               
               
                   
               
               
                  1201 
                 attttccctg ggacagtacc aaggaggaaa gaacccaatt acaaaagcaa aaaactgatg 
               
               
                   
               
               
                  1261 
                 aatacttcag aatgaaactg cagtggaaat ccatcagcca ggaacaagag aaaagaaatt 
               
               
                   
               
               
                  1321 
                 cgaggttaag agattacaga agtcttatcg aaaaagatgt taacagaaca gatcgaacaa 
               
               
                   
               
               
                  1381 
                 acaagtttta tgaaggccaa gataatccag ggttgatttt acttcatgac attttgatga 
               
               
                   
               
               
                  1441 
                 cctactgtat gtatgatttt gatttaggat atgttcaagg aatgagtgat ttactttccc 
               
               
                   
               
               
                  1501 
                 ctcttttata tgtgatggaa aatgaagtgg atgccttttg gtgctttgcc tcttacatgg 
               
               
                   
               
               
                  1561 
                 accaaatgca tcagaatttt gaagaacaaa tgcaaggcat gaagacccag ctaattcagc 
               
               
                   
               
               
                  1621 
                 tgagtacctt acttcgattg ttagacagtg gattttgcag ttacttagaa tctcaggact 
               
               
                   
               
               
                  1681 
                 ctggatacct ttatttttgc ttcaggtggc ttttaatcag attcaaaagg gaatttagtt 
               
               
                   
               
               
                  1741 
                 ttctagatat tcttcgatta tgggaggtaa tgtggaccga actaccatgt acaaatttcc 
               
               
                   
               
               
                  1801 
                 atcttcttct ctgttgtgct attctggaat cagaaaagca gcaaataatg gaaaagcatt 
               
               
                   
               
               
                  1861 
                 atggcttcaa tgaaatactt aagcatatca atgaattgtc catgaaaatt gatgtggaag 
               
               
                   
               
               
                  1921 
                 atatactctg caaggcagaa gcaatttctc tacagatggt aaaatgcaag gaattgccac 
               
               
                   
               
               
                  1981 
                 aagcagtctg tgagatcctt gggcttcaag gcagtgaagt tacaacacca gattcagacg 
               
               
                   
               
               
                  2041 
                 ttggtgaaga cgaaaatgtt gtcatgactc cttgtcctac atctgcattt caaagtaatg 
               
               
                   
               
               
                  2101 
                 ccttgcctac actctctgcc agtggagcca gaaatgacag cccaacacag ataccagtgt 
               
               
                   
               
               
                  2161 
                 cctcagatgt ctgcagatta acacctgcat gatcactgtt cttgcttttt tgggaagaga 
               
               
                   
               
               
                  2221 
                 cactttgttg caaccctttt tcaagtactt gaaagttgaa aatttgaaat cttggtattg 
               
               
                   
               
               
                  2281 
                 atcatgcttt aaggtttatg taaagaaagt gtactgatgt tcttacatta aagctttaca 
               
               
                   
               
               
                  2341 
                 aagatttaaa ctaattattt ttgtagttac ttctaccaaa tagcctttcc ttttcgataa 
               
               
                   
               
               
                  2401 
                 cattcctcag tatttttata gccaagtaca ttttattttc ttgctgatga actggaattg 
               
               
                   
               
               
                  2461 
                 gataaatatt gcaagtggat gagttggaaa ttatgcactt tgaaaaacat tcactttgtt 
               
               
                   
               
               
                  2521 
                 taagcttatt gggtttcaga tttgattaaa ttaaatgtgg aggctttcta tagcattcta 
               
               
                   
               
               
                  2581 
                 agctgagaag tagattgtta cccagtaatg aaataaaaaa taaaaacaaa aggatttttt 
               
               
                   
               
               
                  2641 
                 tctctattgt ttacgacagt actcagctta aatatttatg ctggtcaaat gtgatttaaa 
               
               
                   
               
               
                  2701 
                 ttggacattt tcatcaatgc agtctaatgt gtagataaat atttcaacca taataagtgg 
               
               
                   
               
               
                  2761 
                 attggcagta tattttttac attgaacttt tcttcacttg tatataaaga ttatatataa 
               
               
                   
               
               
                  2821 
                 gtacttattt atgagcataa gaaaggttag gcatattttc attaactgaa taaacgactt 
               
               
                   
               
               
                  2881 
                 gatttatata acctggttta tcaaaattta acatggcttc agtatgagat ctttttcaaa 
               
               
                   
               
               
                  2941 
                 actattttct taaacattta tttcatgaga ttatgttcaa ccctgtacct ggtgtaattt 
               
               
                   
               
               
                  3001 
                 taaaattaat tgcttgtaac ctcactttac taataatgtt tattatcttt cctaataatg 
               
               
                   
               
               
                  3061 
                 cattaactga ttaatcaggt gtttaaattt ttataaaata ctcttgcaaa aagtttattt 
               
               
                   
               
               
                  3121 
                 gaaaaatttc tagatggtct catgagtttc aaaataataa tttttgcgta tgaacaaagc 
               
               
                   
               
               
                  3181 
                 tgttgttttt accatgcagt attgcatgat tttaagttat gtggaattaa cataactgat 
               
               
                   
               
               
                  3241 
                 tttgttttaa ttgtaagttg ttaactcctg tatatatcat taaaataaat ctgaagttga 
               
               
                   
               
               
                  3301 
                 agtagtgttt ttagttaaat tatacttaga aatagtctgc ttttttaaaa ttttttttct 
               
               
                   
               
               
                  3361 
                 tgagaaagag tcttgctctg ttgcccaggc tggagtgcag tggcgcagtc ctggctcact 
               
               
                   
               
               
                  3421 
                 gcagcctccg ccttctgggt tcaagcgatt ctcctgtctc agcctcccga gcagctggga 
               
               
                   
               
               
                  3481 
                 ctacaggctt gtgccatcgc gcctgactaa tttttgtatt ttgagtagag atggggtttc 
               
               
                   
               
               
                  3541 
                 accatgttgg ccaggctggt ctcgaactct tgacctcaag tgatccactc gcttcagcct 
               
               
                   
               
               
                  3601 
                 cccaaagtgc tgagattaca ggtgtgagcc actgtgcccg gctaattctt taatagaaga 
               
               
                   
               
               
                  3661 
                 aaaaacatcc aagatggacc tcaattcatc tcttattttt atatgattaa aatgataatc 
               
               
                   
               
               
                  3721 
                 tggccgggcg cggtggctca cgcctgtaat cccagcactt tgggaggccg aggcgggcgg 
               
               
                   
               
               
                  3781 
                 atcacgaggt caggagatcg agaccatccc ggctaaaacg gtgaaacccc gtctctacta 
               
               
                   
               
               
                  3841 
                 aaaatacaaa aaattagccg ggcgtagtgg cgggcgcctg tagccccagc tacttgggag 
               
               
                   
               
               
                  3901 
                 gctgaggcag gagaa-ggcg tgaacccggg aggcggagct tgcagtgagc cgagatcccg 
               
               
                   
               
               
                  3961 
                 ccactgcact ccagcctggg cgacagagcg agactccgtc tcaaaaaaaa aaaaaaaaaa 
               
               
                   
               
               
                  4021 
                 atgataatct gaataagtta tggaaatgaa aaccatcctt tttataactg aaaaaaaatt 
               
               
                   
               
               
                  4081 
                 ttcattagca tggaaatggg cacagtgttg ccttgaaaga tacagttatt tgactcagta 
               
               
                   
               
               
                  4141 
                 aagcagctta ttacaactga tgctaatagt atagagaaaa aagttgtgca gttctaaaat 
               
               
                   
               
               
                  4201 
                 ggtcctagag attgactttt ttcccccaag aaagttaggg aacaaaacga acttttttcc 
               
               
                   
               
               
                  4261 
                 tggttgagca ttaactgaca atcacgacag tagaaccgtt agagtttagt ttttaatatt 
               
               
                   
               
               
                  4321 
                 atgtgtgtta tctttcatca gttaataatg agtaagccta ttcagaaaaa gaacataaac 
               
               
                   
               
               
                  4381 
                 tgatcaaaaa ctcagcatct ccagcctttc atttcctgct attcaggaaa ttgcttagaa 
               
               
                   
               
               
                  4441 
                 catcttgatg tcctccttgt tcttcctgga cagtgacttt ttgggagttt gttcctgctg 
               
               
                   
               
               
                  4501 
                 cgtaatgtga tacccacttc agattttttt tttatcaata catttagtaa gttgaacttc 
               
               
                   
               
               
                  4561 
                 tgtcaagttt tattacaaaa ttacttgtta aaacaatttt tactaaactg catttctatc 
               
               
                   
               
               
                  4621 
                 tagcatattt ttgatatgga agtgatagta tagtatagtt ccaggagaag tcttaaatca 
               
               
                   
               
               
                  4681 
                 gtccacagag tccagttagc aaatactctg tgccattaag attgctaaaa tacacagttc 
               
               
                   
               
               
                  4741 
                 aggtaaattt actagcgttt tttaaaggtt tatttgtttt cacaagatgc tctgtccaca 
               
               
                   
               
               
                  4801 
                 cccttataac atgtaaaata ttgtgtgctg tattatgtgg taaagttgtt aaaattcagt 
               
               
                   
               
               
                  4861 
                 ttctaacatt aacttaaaag tacagacaat ctaacatgat gatttgactt acaaactttc 
               
               
                   
               
               
                  4921 
                 aactaaattt atgatggctt taaagcagtg cactgaatag aaaccatact ttgagtaccc 
               
               
                   
               
               
                  4981 
                 atacagccat ttttcacttt tactacaata ttctataaat cacatgagat atttaacact 
               
               
                   
               
               
                  5041 
                 ttattataaa ataggctttg tgttagatga ttttgcccaa atgtaaacta atgtagtgtt 
               
               
                   
               
               
                  5101 
                 ctgagcatgt ttaagttagg gtaggctaaa ctatgtttgg taggttagat gtattaaaag 
               
               
                   
               
               
                  5161 
                 catttttgat taatgatgtc ttcaatttat gatgtgttta ttggaacata acctcaatat 
               
               
                   
               
               
                  5221 
                 aagttgaaaa gcatacgtat tttcaattct ggcatgaacc tatgggaatc ttttgcattt 
               
               
                   
               
               
                  5281 
                 aagaacctcc ccattttaat aatttcatgg gtctaagatt cttcatctgt ttataaggaa 
               
               
                   
               
               
                  5341 
                 ctttagtctt agtgattaga gactaaattt ttttttgagc agtaagaaaa cagccttttg 
               
               
                   
               
               
                  5401 
                 ggacagatag tgagtgattc ttaggaactt gacattgcca agaaatttta tagatgccga 
               
               
                   
               
               
                  5461 
                 agaattctta tgtgaaattc acataagcat gcccattact aaagacagtt tgtataaagt 
               
               
                   
               
               
                  5521 
                 aaccctaaat gtttactgag gaacctacag cttcaactga cttacgcgca gatatgtacc 
               
               
                   
               
               
                  5581 
                 aggagaacat cattttagct tgggcgtctt tacttggggt tttcagagga tccaggaacc 
               
               
                   
               
               
                  5641 
                 tcactgtatg caaagtcttg tggatgtacc tgaatgtttt tggaggcagg tcacatagtt 
               
               
                   
               
               
                  5701 
                 tctgaaagtg ttctcttatt ttcctcaaat gtaggtaacc attgttacaa gttatttaac 
               
               
                   
               
               
                  5761 
                 aggagaatag taacaatgtc taacttatgc taatgatttt gtgtgctgag ctcccattaa 
               
               
                   
               
               
                  5821 
                 ttaaaatgtc ttcagaaaaa aaaaaaaaaa aa 
               
               
                   
               
            
           
         
       
     
     Ngo et al.,  Science  360,1133-1136 (2018) is incorporated herein by reference. 
     While the foregoing invention has been described in some detail for purposes of clarity and understanding, it will be appreciated by those skilled in the relevant arts, once they have been made familiar with this disclosure, that various changes in form and detail can be made without departing from the true scope of the invention in the appended claims. The invention is therefore not to be limited to the exact components or details of methodology or construction set forth above. Except to the extent necessary or inherent in the processes themselves, no particular order to steps or stages of methods or processes described in this disclosure, including the Figures, is intended or implied. In many cases the order of process steps may be varied without changing the purpose, effect, or import of the methods described. 
     All publications and patent documents cited herein are incorporated herein by reference as if each such publication or document was specifically and individually indicated to be incorporated herein by reference. Citation of publications and patent documents (patents, published patent applications, and unpublished patent applications) is not intended as an admission that any such document is pertinent prior art, nor does it constitute any admission as to the contents or date of the same.