Abstract:
Differences in gene expression in control and asthma patients to profile, differentiate, evaluate, etc. patients with exacerbated asthma and stable asthma.

Description:
This invention was made with government support under Grant Nos. R01AI46652-01A1 and R01HL72987 awarded by the National Institutes of Health. The government has certain rights in the invention. 
    
    
     In accordance with 37 CFR §§1.77, 1.821-1.824, and 1.52(e), applicants state that the Sequence Listing for this application is submitted only in electronic form on a CD-ROM and herein incorporate by reference the entire Sequence Listing contained on the CD-ROM. The only material on the CD-ROM is the Sequence Listing for the instant patent application, which was created on Dec. 20, 2005 and has 616 KB. Applicants further state that the Sequence Listing information recorded and submitted herein in computer readable form is identical to the written (CD-ROM) sequence listing. 
     FIELD OF THE INVENTION 
     The invention is directed to asthma gene expression profiles. 
     BACKGROUND 
     Asthma is the most common chronic disease of childhood and has a strong genetic component. Microarray technology has been used previously to identify gene profiles associated with asthma but were limited to adult patients and to RNA derived from peripheral blood mononuclear cells. Because asthma most often begins in childhood, genes identified in adults may not represent genes important for asthma development. 
     SUMMARY OF THE INVENTION 
     Microarray technology was applied to childhood asthma. Gene profiles, also referred to herein as signatures, associated with childhood stable and exacerbated asthma, also referred to herein as acute asthma, were determined. It was also determined whether the same genes induced during stable asthma were expressed during asthma exacerbations, or whether a distinct set of genes were activated during an asthma exacerbation. Microarray technology in a group-averaged approach, and confirmatory reverse transcription polymerase chain reaction (RT-PCR) at an individual patient level, provided global gene expression profiles in respiratory epithelial cells derived from nasal respiratory epithelial cells in normal and asthmatic children. 
     Children with stable asthma (asthma-S), children experiencing an asthma exacerbation (asthma-E), and non-asthmatic children were evaluated. RNA was prepared from nasal respiratory epithelial cells isolated from each child, initially analyzed as pooled samples from the three groups. Further validation was performed on individual patient samples using microarrays and RT-PCR. 
     Distinct gene clusters were identifiable in individual and pooled asthma-S and asthma-E samples. Asthma-E samples demonstrated the strongest and most reproducible signatures, with 314 genes of 34,886 measured as Present on the chip, demonstrating induction or repression of greater than two-fold with p&lt;0.05 in each of four individual samples. Asthma-S-regulated genes encompassed genes that overlapped with those of Asthma-E, but were fewer (166) and less consistent with respect to their behavior across the Asthma-E patient samples. Independent gene expression signatures were reflective of cells and genes poised or committed to activation by an asthma attack. 
     The information is useful for asthma diagnosis, evaluation of status and treatment response, and design of prophylaxis and therapy. These and other advantages will be apparent in light of the following figures, tables, and detailed description. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. 
         FIG. 1  shows hierarchical clustering and relative expression of genes highly expressed in childhood asthma. 
         FIG. 2  shows quantitative reverse transcription polymerase chain reaction analysis of selected genes. 
         FIG. 3  shows hierarchical clustering of genes highly expressed in individual children with stable and acute asthma compared with controls. 
         FIG. 4  shows selected upregulated and downregulated genes compared with normal controls. 
     
    
    
     DETAILED DESCRIPTION 
     Applicants incorporate by reference in its entirety Guajardo et al., Altered gene expression profiles in nasal respiratory epithelium reflect stable versus acute childhood asthma, J. Allergy Clin Immunol 2005; 115:243-53. 
     Healthy and asthmatic children attending the clinics and emergency department of Cincinnati Children&#39;s Hospital Medical Center (CCHMC) were evaluated. Asthmatic children were either stable, indicated by the substantial absence of wheezing, or exacerbated, indicated by wheezing. Asthma was diagnosed according to American Thoracic Society criteria. Participants were included in one of three groups: 1. Stable allergic asthma (asthma-S group, N=10) inclusion criteria: a. younger than 18 years of age, b. physician-diagnosed asthma currently stable (not wheezing), and c. positive skin prick testing to any of the allergens from an environmental panel that included dust mite, molds, cat, dog, feathers, weeds and ragweed, tree pollens and grass allergen extracts (Hollister-Stier Laboratories, Spokane Wash.); 2. Exacerbation of asthma (asthma-E group, N=10) included children acutely wheezing with similar inclusion criteria to the asthma-S group with the exception of skin test positivity (skin testing was not performed in this group because it could further deteriorate the acute status of asthma); and 3. Healthy children (control group, N=10) inclusion criteria: a. younger than 18 years of age, b. healthy with no acute infections or major chronic illnesses, and c. negative results to the above-described environmental skin test prick panel. Exclusion criteria to participate in the study included a. 18 years of age or older, b. the use of nasal or systemic steroids within the last 30 days, c. nasal malformations/tumors, and d. acute infectious disease present in the asthma-S or control groups. Children with a concurrent diagnosis of allergic rhinitis were excluded if they had used nasal steroids within 30 days. The use of inhaled steroids was not interrupted for this study. Skin prick testing was performed in the asthma-S and control groups using DermaPiks (Greer Laboratories, Lenoir N.C.). Histamine (1 mg/ml) and normal saline (0.9% NaCl) were used as positive and negative controls. Reactions were considered positive if there was an erythematous base with a wheal ≧3 mm in diameter. 
     Nasal mucosa sampling was performed using a CytoSoft Brush (Medical Packaging Corp., Camarillo Calif.) and the sample was immediately taken to the laboratory for processing. Samples from children in the group experiencing an asthma exacerbation (asthma-E) were taken within one hour of arrival to the emergency room and before any steroids were given. The cells were suspended in phosphare buffered saline (PBS) and an aliquot was stained with Diff-Quick (Dade Behring Inc, Newark Del.). Cell counting was performed in five high power fields (hpf) and the relative percentages of cell types were calculated. A total eosinophil cell count was also performed. 
     RNA was isolated from the nasal mucosa sample using TRIZOL according to manufacturer instructions (TRIZOL Reagent, Invitrogen Corporation, Carlsbad Calif.). Average RNA yield was 42.6 μg. In one embodiment, two micrograms of RNA from each subject were pooled to form a group sample containing 20 μg. The three samples (Control, Asthma-S, and Asthma-E) were then submitted to the Affymetrix Genechip Core Facility at Cincinnati Children&#39;s Hospital Medical Center for processing and microarray hybridization using the HG-U133A GeneChip (Affymetrix, Santa Clara Calif.) according to Affymetrix guidelines. The HG-U133A chip microarray had a total of 22,215 probe sets (excluding controls) that identified 14,285 genes of which 12,735 are known. In addition, four individual samples from each group (Control, Asthma-S and Asthma-E) were submitted to the Affymetrix Genechip Core Facility at CCHMC for microarray hybridization using the HG-U133_plus 2 GeneChip (Affymetrix) according to Affymetrix guidelines. The HG-U133_plus 2 chip microarray had a total of 54,675 probe sets. 
     Scanned output files were analyzed using Microarray Suite 5.0 software (Affymetrix). From cell image data files, gene transcript levels were estimated as the Signal strength using the MAS5.0 (Affymetrix). Global scaling was performed to compare genes from chip to chip. Arrays were scaled to the same target intensity value (Tgt=1500) per gene and analyzed independently. 
     Second-stage data analyses were performed using GeneSpring software (Silicon Genetics, Redwood City Calif.). Initially, data from pooled asthma-S and asthma-E groups were analyzed by looking for genes that were most different in expression relative to the control group sample. A total of 299 cDNAs corresponding to genes that were three-fold up- or down-regulated in the asthma-S or asthma-E groups when compared to the control group were identified. These 299 highly expressed cDNAs were clustered according to their expression profiles along the GI A-P axis by using hierarchical clustering algorithms as implemented in the GeneSpring program. Clustering of the dataset was by several different normalization methods. The use of raw ratios of hybridization versus reference or the log2 of these ratios provided an assessment of genes based on their levels of expression. These 299 highly expressed cDNAs were clustered according to their relative expression profiles using normalization of raw ratios or the log2 of these ratios to the expression of the control group. The number of immune-related genes was obtained for each cluster. 
     GeneChip data from individual RNA samples were examined by a statistical approach designed to test the hypothesis that genes whose expression was altered in the individual samples would parallel that observed in the pooled samples. Next-generation human HG-U133-plus2 GeneChips (human HG-U133_plus2) were analyzed using MicroArraySuite 5 and the resulting GeneChip intensities were exported to GeneSpring 7.0 and normalized to the median expression level among the four control samples. Genes whose expression varied according to diagnostic group were obtained by first selecting genes that the Affymetrix algorithm reported to be “Present” in at least two gene chips. This returned 32,435 genes from the 54,675 on the chip. Next, an approximately normal distribution of gene expression values was generated by representing each gene&#39;s expression as the log of its expression Signal as measured by Microarray Suite. ANOVA was applied to the conditions with a probability of less than 0.01 (acute vs. stable vs. control) to obtain genes differentially expressed between conditions in at least three out of five chips. Each of these lists were further filtered for median expression being at least two-fold different between the two conditions. The resulting gene list of 1378 genes was then subjected to cluster analysis using Standard Correlation as implemented in GeneSpring. 
     Gene specific primers (designed using Beacon Designer software) were chosen to span at least one intron in the genomic sequence to enable the mRNA-derived product to be distinguished from any possible contaminating genomic product. The sequences of primers for the target genes were as follows: lymphotactin (NM — 003175) AATCAAGACCTACACCATCAC SEQ ID NO: 1 (sense) and TTCCTGTCCATGCTCCTG SEQ ID NO: 2 (anti-sense); histamine 4 (H4) receptor (NM — 21624) GGTGTGATCTCCATTCCTTTG SEQ ID NO: 3 (sense) and GCCACCATCAGAGTAACAATC SEQ ID NO: 4 (anti-sense); retinoic acid receptor (RARα) (hCT2294851) AGGAGACTGAGATTAGC SEQ ID NO: 5 (sense) and AAGAAGAAGGCGTAGG SEQ ID NO: 6 (anti-sense); CXCL11 (NM — 005409) GCTACAGTTGTTCAAGGCTTCC SEQ ID NO: 7 (sense) and TTGGGATTTAGGCATCGTTGTC SEQ ID NO: 8 (anti-sense); and ubiquitin C (UBC) (M26880) ATTTGGGTCGCGGTTCTTGSEQ ID NO: 9 (sense) and TGCCTTGACATTCTCGATGGT SEQ ID NO: 10 (anti-sense). Prior to cDNA synthesis (using SuperScript U, RNase H, Invitrogen), 1-2 ug of each RNA sample was pretreated with DNase I (Invitrogen) to eliminate any potential contaminating genomic DNA. RT-PCR analysis was conducted with the iCycler (Bio-Rad) using the “iQ SYBR Green Supermix” Taq polymerase mix (Bio-Rad). The amount of double-stranded DNA product, indicated by SYBR Green fluorescence, was measured at the end of each extension cycle. The relative message levels of each target gene were normalized to the UBC housekeeping gene. 
     Statistical differences between the relative expression levels of RARα, H4R, CXCL11, and lymphotactin genes among the different groups were determined by ANOVA (one-way) of the means and standard error values. This was followed by the Bonferroni procedure to allow for multiple comparisons. A p-value of &lt;0.05 was considered significant. 
     The mean age in years for the Control (n=10), Asthma-S (n=10), and Asthma-E (n=10) group subjects was 11.7 (SD±2.3), 11.4 (SD±3.4), and 10.1 (SD±6.17) respectively. The gender (male:female) and race (AfricanAmerican:Caucasian) ratios were 7:3 and 8:2 for the control group; 7:3 and 5:5 for the Asthma-S group, and 6:4 and 9:1 for the Asthma-E group. There was no statistical difference between the groups. The children in the asthma-S and asthma-E groups were predominantly African American males, which agreed with published data regarding the racial and gender distributions of childhood asthma in urban environments. 
     The cellular composition of the nasal respiratory epithelial sample was determined for each subject. For the control group, the average number of cells/hpf (400×) was 265 (SD±104) with 97.7% epithelial cells, 1.84% polymorphonuclear leukocyte cells (PMN), 0.36% squamous cells, and 0.07% eosinophils. For the Asthma-S group the average number of cells/hpf was 219 (SD±87) with 96.3% epithelial cells, 3.32% PMN, 0.30% squamous cells, and 0.09% eosinophils; and for the Asthma-E group the average number of cells/hpf was 154 (SD±69) with 92.3% epithelial cells, 7.24% PMN, 0.18% squamous cells, and 0.25% eosinophils. Epithelial cells represented greater than 92% of the total cells isolated in all groups. There were higher percentages of PMN and eosinophils in samples from children experiencing an asthma exacerbation, however, they remained minor populations (7.2% and 0.25%, respectively) compared with the percentage of respiratory cells (92.3%) and the differences were not statistically significant. Overall, a lower average of total cells was recovered from the nasal samples of children experiencing an asthma exacerbation. While not being bound by a specific theory, this may be due to excessive mucus. RNA was isolated from each sample with an average yield of 42.6 μg per sample from one nostril. Two μg of RNA were pooled from each subject in each group and the three pools were subjected to microarray analysis (HG-U133A Affymetrix GeneChip). 
     In the asthma-S and asthma-E pooled groups, the expression of 253 (2.0%) of the known genes changed by at least three-fold in either group. The mean raw expression of these genes was 2076 (SD 4322) with a range of 17.4 to 67068 and a median and mode of 1192 and 1903, respectively. 
     The microarray data are summarized in  FIG. 1 . Hierarchical clustering and relative expression of genes highly expressed in childhood asthma are shown in panel A. Colors are graded to indicate increased (red) or decreased (blue) expression relative to reference. Relative expression in a given cluster is shown in panel B. The y-axis represents expression normalized to control expression. Cluster analysis examining gene profiles revealed eight distinct clusters of genes regulated in stable and acute childhood asthma. The genes in cluster or group A (N=33) were similarly upregulated in both asthma-S and asthma-E. In cluster B (N=55), genes were upregulated in asthma-S, and further induced in asthma-E. Cluster C genes (N=25) were unchanged in asthma-S, but upregulated in asthma-E. Cluster D genes (N=77) were downregulated in asthma-S, but unchanged in asthma-E. Cluster E genes (N=31) were upregulated in asthma-S, but unchanged in asthma-E. Cluster F genes (N=4) were upregulated in asthma-S, but downregulated in asthma-E. Cluster G genes (N=35) were unchanged in asthma-S, but downregulated in asthma-E. Cluster H genes (N=39) were downregulated in both asthma-S and asthma-E. 
     Cluster A (N=33), representing genes similarly upregulated in both asthma-S and asthma-E, contained 32 known genes (0.25% of the total known genes). Of these genes, 27.3% were immune-related and 21.2% were involved in signal transduction. The genes in Cluster B that were upregulated during asthma exacerbations (asthma-E) to a higher extent than in asthma-S were comprised of 43.6% immune-related genes. The genes in Cluster C that were upregulated during asthma exacerbations (asthma-E), but unchanged in stable asthma, were comprised of 44% immune-related genes. Clusters D-H were each comprised of less than 6.5% immune-related genes. Genes in Cluster E that were upregulated in children with stable asthma, but unchanged during asthma exacerbations, included 6.5% immune related genes. The genes in this profile included mainly signal transduction genes and cell function enzymes. Clusters D, F, G and H, which contain genes that were downregulated, consist largely of genes involved in basic cell functions and unknown genes. 
     Distinct clusters of genes that were differentially regulated in childhood asthma were identified, as shown in Tables 1-14. Distinct sets of genes were activated during stable vs. exacerbated asthma, establishing that exacerbated asthma status is distinguished based on the occurrence of strong gene expression signatures in nasal epithelial samples. Stable asthma status also exhibited differential signatures but with more variability. While not bound by any theory, this may suggest clinical and or mechanistic heterogeneity among the patients. 
     In the exacerbated asthma pooled sample, 12 genes were upregulated at least two-fold (Table 15) and 50 genes were upregulated at least three-fold (Table 16) as compared to the control pooled sample. Fourteen genes in the exacerbated asthma pooled sample were downregulated by at least two-fold (Table 17) and 7 genes were downregulated by at least three-fold (Table 18), compared to the control pooled sample. In the stable asthma pooled sample, 7 genes were upregulated by at least two-fold (Table 19) and 11 genes were upregulated by at least three-fold (Table 20) compared to the control pooled sample. Also, 6 genes in the stable asthma pooled sample were downregulated by at least two-fold (Table 21) and 4 genes were downregulated by at least three-fold (Table 22) compared to the control pooled sample. 
     Reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed expression of genes identified by microarray. For the microarray analysis, equivalent amounts of RNA were pooled from individuals in each group. All individual RNA samples isolated from nasal mucosal cells from participants from the control (N=10), asthma-S(N=10), and asthma-E (N=10) groups were analyzed by RT-PCR for expression of each gene. Four genes (CXCL11, RARα, H4R, and lymphotactin) were examined: one induced in the asthma-E group exclusively (Cluster C), one induced in the asthma-S group exclusively (Cluster E), and two simultaneously induced in both groups (Cluster A). 
     Quantitative RT-PCR analysis is shown in  FIG. 2 , with the y-axis in each graph representing relative message levels, normalized to the average of duplicate UBC message levels. RT-PCR confirmed increased expression of the selected genes in asthma-S and/or asthma-E. CXCL11 expression was increased in asthma-E to a greater extent than asthma-S. RARα was induced in asthma-S, but not asthma-E, and lymphotactin was induced equally in asthma-S and asthma-E. The RT-PCR data validated the genes identified by chip array and confirmed differential expression in the asthma-E and asthma-S groups. 
       FIG. 3  shows hierarchical clustering of genes highly expressed in individual children with stable and exacerbated asthma compared with controls, with colors graded to indicate increased (red) or decreased (blue) expression relative to reference. The clustering results from the individual samples are presented beside the data from the RNA samples pooled from each group (N=10). As shown, the data from the individual samples were substantially consistent both between individuals and when compared to the pooled sample data. A stepwise filtering method was used to derive a total of 161 genes whose expression was significantly different between the groups (ANOVA, p&lt;0.01), and in addition was of sufficient magnitude to increase or decrease by at least two-fold in 3 of the 4 individual samples. 
     In the exacerbated asthma individual group (versus the pooled group), 88 genes were upregulated and 53 genes were downregulated compared to the control group. In the stable asthma group, 21 genes were upregulated and 12 genes were downregulated. More specifically, in the exacerbated asthma group, 9 genes exhibited at least a two-fold increase (Table 1) and 79 genes showed at least a three-fold increase (Table 2) compared to controls. Also, 36 genes were decreased by at least two-fold (Table 3) and 15 genes were decreased by at least three-fold (Table 4) compared to controls. In the stable asthma group, 11 genes were upregulated by at least two-fold (Table 5) and 10 genes were upregulated by at least three-fold (Table 6) compared to controls. Also, 8 genes were downregulated by at least two-fold (Table 7) and 4 genes were downregulated by at least three-fold (Table 8) compared to controls. Many of the changes in gene expression were specific to either stable or exacerbated asthma in that gene expression did not change in the other group or had the opposite change in expression. For example, 70 genes that exhibited at least a two-fold increase in the exacerbated asthma group showed no change of expression in the stable asthma group (Table 9). Also, 50 genes were downregulated by at least two-fold in the exacerbated asthma group but were unchanged in the stable asthma group (Table 10). For stable asthma specific genes, 4 genes were upregulated by at least two-fold while unchanged in the exacerbated asthma group (Table 11) and 9 genes were downregulated by at least two-fold in the stable asthma group and remained unchanged in the exacerbated asthma group (Table 12). In some cases, the direction of change in gene expression was the same for both the stable and exacerbated asthma groups. For example, 16 genes showed at least a two-fold increase in expression in both groups compared to control groups (Table 13). Four genes exhibited an inverse in expression levels, with a gene upregulated by at least two-fold in the exacerbated asthma group and downregulated by at least two-fold in the stable asthma group, or vice versa (Table 14). 
     Among the 161 most upregulated and downregulated genes (at least three-fold change, p&lt;0.01) that were consistent in at least 3 of the 4 samples, classes of genes were evaluated to determine if a particular class of genes was overrepresented. Two classes of genes were noted as shown in  FIG. 4 . Selected upregulated immune-related genes (A) and downregulated cilia-related genes (B) compared with controls in at least 3 out of 4 samples. Among the upregulated genes, 37 immune-related genes were consistently upregulated at least three-fold ( FIG. 4A ). Among the downregulated genes, 9 cilia-related genes were consistently downregulated at least three-fold ( FIG. 4B ). 
     Respiratory epithelial cells serve as an accessible alternative proxy for lower respiratory epithelium, even if they may not fully represent the genes that are expressed in the lungs of children with asthma. Many of the genes that were found to be induced in childhood asthma have been implicated in the pathogenesis of asthma in other studies, including arginase, SOCS-3, complement 3a receptor, and lymphotactin. For the chip array analysis, both pooled samples derived from equivalent amounts of RNA from each individual in each group, as well as individual samples, were utilized. The gene expression signatures obtained from the individual samples agreed with the pooled samples. RT-PCR of the individual RNA samples further validated findings and RT-PCR confirmed the chip array data. 
     The percentage of immune related genes was examined in each cluster. In the pooled samples, clusters that included genes induced specifically in either asthma exacerbations (Cluster C) or genes that were induced at a higher level during asthma exacerbations (Cluster D) contained the highest percentages and absolute numbers of immune-related genes. This was confirmed by further chip array analyses of the individual samples. The immune-related genes were overrepresented among the most upregulated genes. Genes that are not classified as immune genes may have direct or indirect effects on the immune system. Asthma-E samples demonstrated the strongest and most reproducible signatures and these signatures were distinct from Asthma-S. Among the most downregulated genes, cilia-related genes were overrepresented. Because the respiratory epithelium is often damaged in asthma and there is an overproduction of mucus, one might predict that genes important in ciliary function would be induced. While not being bound by any theory, downregulation in cilia-related genes may contribute to asthma pathogenesis by impairing mucus clearance. Alternatively, downregulation of cilia genes may be a response to damage and may be used for repair or remodeling. 
     Each cluster identifies novel potential target candidate genes for childhood asthma. In Cluster A, the H4 receptor gene was induced nearly ten-fold. This gene was recently cloned and found to be expressed in leukocytes, including eosinophils, as well as the lung and it is involved in childhood asthma. In contrast, the H1, H2, and H3 receptors were not induced. Also in Cluster A, SOCS-3 was induced nearly nine-fold. SOCS-3 expression correlates strongly with the pathology of asthma and atopic dermatitis, as well as serum IgE levels in allergic human patients. The complement 3α receptor 1 gene SEQ ID NO: 65 in Table 2 was induced. In a previous study examining the role of C3α in asthma, C3α levels were increased following segmental airway challenge in sensitized adults with asthma, and the receptor is also regulated during the effector phase of asthma. Several IFN-induced proteins were also induced in this cluster of genes induced in asthma-E to a greater level than asthma-S. Because asthma exacerbations in children can be associated with upper respiratory viral infections, some of these may represent an IFN-mediated anti-viral response. Genes that were induced exclusively during asthma exacerbations (Table 9) included integrin α4 as well as several chemokines and chemokine receptors. Integrin α4 (CD49d), which is important for eosinophil survival and recruitment, was induced 8.6 fold in children experiencing asthma exacerbation, but not in children with stable asthma. In contrast, genes that were induced in asthma-S, but not asthma-E (Table 11) did not include chemokine receptors nor chemokines. The most strongly induced gene in this cluster was the gene encoding RARα, which was induced approximately 28-fold compared to non-asthmatic children. Retinoids exert multiple effects upon lung differentiation and growth, and this receptor may contribute to lung repair or remodeling in children with ongoing stable asthma. Another gene in this cluster is arginase, supporting its roles as a mediator of childhood asthma. In a recent study, adults with stable asthma had increased arginase expression in their lungs and BALF compared with normal controls. In a previous study utilizing microarray analysis to identify genes important in asthma RNA isolated from peripheral blood mononuclear cells from adults with atopic asthma, allergic rhinitis but not asthma, and healthy controls was analyzed. Decreased levels of interferon α/β receptor (ratio 0.42) were found, similar to results in Cluster H. 
     Although environmental factors likely contribute to the different prevalence rates, genes with large allele frequency differences between a Caucasian population and a Han Chinese population may be partly responsible for the current variation in asthma susceptibility. One-hundred and sixty-one known genes identified by microarray data were examined for large allele frequency differences between Caucasian and Han Chinese populations. Allele frequencies of the single nucleotide polymorphisms (SNPs) within each gene in Caucasians and in Han Chinese were retrieved from the public HapMap database (http://www.hapmap.org). F ST  was calculated as F ST =σ 2 /pq, where σ 2  is the variance in allele frequency, and p and q are the average allele frequency of each allele among subpopulations, respectively. When comparing two subpopulations with two alleles in each, the variance in allele frequency equals to σ 2 =(p 1 −p 2 ) 2 /4, where p 1  is the allele frequency in the first subpopulation, and p 2  is the frequency of the same allele in the second subpopulation. Therefore, the F ST  was calculated by F ST =(p 1 −p 2 ) 2 /(4p(1−p)). The sample size obtained from HapMap project was large, i.e., 60 and 45 unrelated Caucasians and Han Chinese were genotyped, respectively, and allowed for calculation of F ST  without additional corrections. F ST  has a theoretical minimum of 0, indicating no genetic divergence, and a theoretical maximum of 1, indicating fixation for alternative alleles in different subpopulations. The observed F ST  is usually much less than 1 in human subpopulations. The following qualitative guidelines were used for the interpretation of F ST : 0&lt;F ST &lt;0.05: little genetic differentiation; 0.05&lt;F ST &lt;0.15: moderate genetic differentiation; 0.15&lt;F ST &lt;0.25: great genetic differentiation; and F ST &gt;0.25: very great genetic differentiation. 
     The F ST  for each identified SNPs (from HapMap database) was calculated in each of the 161 most regulated genes related to childhood asthma based on the gene expression profile comparisons. Among the asthma signature genes from the chip array results, there were 43 genes (39%) with large allele frequency differences (F ST &gt;0.15) between Caucasian and Han Chinese populations. Of these 43 genes, 17 had a F ST &gt;0.25 (Table 23) and 26 had a 0.15&gt;F ST &gt;0.25 (Table 24). This proportion is higher than the average genetic differentiation between these two subpopulations. 
     Among these 43 genes, six genes (PDE4B SEQ. ID NO. 27; SPRR2B SEQ. ID NO. 109; ADCY2 SEQ. ID NO. 46; KIF3A SEQ. ID NO. 80; DNAH5 SEQ ID NO. 115; and PLAUSEQ. ID NO. 98) are located in chromosomal regions that have been linked to asthma phenotypes and atopy phenotypes and have been shown to either be regulated during allergic inflammation and/or to regulate release of Th2 cytokines including IL-13. These six genes have been shown to either be regulated during allergic inflammation and/or to regulate release of Th2 cytokines including IL-13. The following summarizes of each gene and its relationship to allergic inflammation and IL-13. 
     Phosphodiesterase 4B (PDE4B): The cyclic nucleotides, cAMP and cGMP, are important second messengers known to control many cellular processes. In inflammatory cells, activation of cAMP signaling has negative modulatory effects on numerous steps required for immune inflammatory responses, including T cell activation and proliferation, cytokine recruitment and recruitment of leukocyte. The cyclic nucleotide signaling system is complex and interlinked with many other pathways. Their signals are tightly controlled by regulating the synthesis and breakdown of these molecules. Phosphodiesterases are the enzymes that degrade and inactivate cyclic nucleotides. The phosphodiesterase 4 (PDE4) family consists of four genes (PDE4A-D) and each gene encodes multiple variants generated from alternate splicing and different transcriptional promoters. The phenotypes of the different PDE4 null mice support unique functions for each PDE4 gene. PDE4B null mice are generally healthy, but peripheral blood leukocytes derived from PDE4B null mice produce very little TNFα in response to LPS. Extensive studies using specific PDE4B inhibitors both in vitro and in vivo have demonstrated a potent anti-inflammatory effect as well as regulation of airway smooth muscle by PDE4B. Given the broad inhibitory effects, pharmacologic manipulation of PDE4 is a promising approach for treating chronic inflammatory conditions including asthma. In animal models of asthma, PDE4 inhibitors have been shown to inhibit airway inflammation and remodeling. A key feature of chronic inflammatory airway diseases such as asthma is mucus hypersecretion. MUC5AC is the predominant mucin gene expressed in healthy airways and is increased in asthmatic patients. Selective PDE4 inhibition was shown to be effective in decreasing EGF-induced MUC5AC expression in human airway epithelial cells. In a placebo-controlled, randomized clinical trial, PDE4 inhibition was found to be efficacious in exercise-induced asthma; the mean percentage fall of FEV1 after exercise was reduced by 41% as compared to placebo. 
     One mechanism by which PDE4 inhibitors exert an anti-inflammatory effect is by inhibiting IL-13 production in allergic diseases by T cells and basophils. In one study, phytohaemagglutinin (PHA)-induced IL-13 release from peripheral blood mononuclear cells from atopic asthma patients was inhibited by rolipram, a PDE4 inhibitor. In another study, rolipram inhibited IL-13 production from PHA- or anti-CD3 plus anti-CD28-stimulated human T cells. Similarly, PDE4 inhibition blocked  Dermatophagoides  pteronyssinus-induced interleukin-13 secretion in atopic dermatitis T cells. 
     Small proline-rich protein 2B (SPRR2B): SPRR genes encode a class of small proline rich proteins that are strongly induced during differentiation of human epidermal keratinocytes in vitro and in vivo. They are encoded by closely related members of a gene family closely linked within a 300-kb DNA segment on human chromosome 1q21-q22 in a region that has been linked to atopy phenotypes. These genes are expressed predominantly in squamous epithelium, where they contribute to the formation of the insoluble cornified crosslinked envelope that provides structural integrity and limits permeability through transglutaminase-induced N-glutamyl)lysine isopeptide crosslinks and interchain disulfide bonds. Studies using primary human and murine cells grown at the air-liquid interface demonstrated that IL-13 directly induces SPRR2B. In fact SPRR2B was one of only four genes that was induced more strongly by IL-13 than IL-4. The fact that SPRR2B was strongly induced by IL-13 supported that it may be important in the pathogenesis of allergic disease. This role for SPRR2b substantiated in a recent study by Drs. Rothenberg and Wills-Karp where SPRR2B was shown to be induced in lungs of mice in a mouse model of asthma in a Stat6-dependent fashion. Thus, SPRR2 is an allergen- and IL-13-induced gene in experimental allergic responses that may be involved in disease pathophysiology. 
     Adenylate Cyclase 2 (ADCY2): This gene encodes a member of the family of adenylate cyclases, which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This enzyme is insensitive to Ca(2+)/calmodulin, and is stimulated by the G protein beta and gamma subunit complex. It is located on chromosome 5p15 in a region that has been linked to atopy phenotypes. Cyclic AMP has a broad range of anti-inflammatory effects on a variety of effector cells involved in asthma. Pharmacologic inhibition of adenylate cyclases inhibited IL-13 production from PHA- or anti-CD3 plus anti-CD28-stimulated human T cells. 
     Kinesin family member 3A (KIF3A): KIF3 is a heterotrimeric member of the kinesin superfamily of microtubule associated motors. This functionally diverse family of proteins mediates transport between the endoplasmic reticulum and the Golgi, transports protein complexes within cilia and flagella, and is involved in anterograde transport of membrane bound organelles in neurons and melanosomes. Embryos lacking KIF3A die at 10 days postcoitum, exhibit randomized establishment of L-R asymmetry, and display numerous structural abnormalities. Interestingly, the KIF3A gene is located on 5q31 in a region that has demonstrated linkage to asthma and atopy in multiple studies. It is located immediately upstream of IL4 and IL13 and conserved non-coding sequences in this area have been implicated in the coordinate transcriptional regulation of IL-4 and IL-13. 
     Dynein, axonemal, heavy polypeptide 5 (DNAH5): DNAH5 is a component of the outer dynein arm of cilia. Mutations in DNAH5 resulting in non-functional proteins have been found to be responsible for primary ciliary dyskinesia. Similar to ADCY2, the DNAH5 gene is located on chromosome 5p15 in a region that has been linked to atopy phenotypes. IL-13 has direct effects on ciliary function, specifically it alters mucociliary differentiation and decreases ciliary beat frequency of ciliated epithelial cells. 
     Plasminogen activator, urokinase (PLAU): PLAU is located on chromosome 10q24 and its gene product, urokinase, is serine protease involved in degradation of the extracellular matrix. Urokinase converts plasminogen to plasmin by specific cleavage of an Arg-Val bond in plasminogen. Recent studies suggest that the plasmin system plays an active role in tissue remodeling by influencing the production of inflammatory mediators and growth factors. Plasmin also degrades the extracellular matrix (ECM), either directly removing glycoproteins from ECM or by activating matrix metalloproteinases (MMPs). Urokinase is synthesized by airway cells, and inflammatory mediators affect its expression. In mouse models of asthma urokinase is induced in the lungs of mice, and in monocytes urokinase is induced in response to IL-4 and IL-13. The role of urokinase in inflammation was further defined in a recent study whereby urokinase gene-targeted mice fail to generate a Th2 immune response following schistosomal antigen challenge. The plasmin system is also involved in eotaxin-mediated chemotaxis of eosinophils. 
     Each of the gene products is expressed in respiratory epithelium. None of these epithelial genes have been studied as potential candidate genes for asthma. 
     In summary, the distinct gene expression profiles in nasal respiratory epithelial cells of children with stable asthma (asthma-S) and children experiencing an asthma exacerbation (asthma-E) provided an overview of the genetic portrait of childhood asthma and the differences in genes important in promoting the development of asthma versus promoting the ongoing phenotype of asthma. Strong gene expression signatures that reflect clinical asthma attack status in readily sampled patient tissues provide a new opportunity for molecular sub-classification and clinical management of asthma patients. Both stabilized and acutely affected asthmatic children exhibited characteristic expression profiles that affect understanding of disease status, treatment response, and new therapies. 
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Exacerbated Asthma two-fold increase 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 EMR2 
                 egf-like module containing, mucin-like, hormone 
                 NM_013447 
                 22 
               
               
                   
                 receptor-like 2 
                   
                   
               
               
                 THBD 
                 thrombomodulin 
                 NM_000361 
                 23 
               
               
                 ZNF407 
                 zinc finger protein 407 
                 NM_017757 
                 31 
               
               
                 ALDH1A3 
                 aldehyde dehydrogenase 1 family, member A3 
                 NM_000693 
                 39 
               
               
                 OLR1 
                 oxidized low density lipoprotein (lectin-like) receptor 1 
                 NM_002543 
                 69 
               
               
                 SCEL 
                 sciellin 
                 NM_144777 
                 77 
               
               
                 PLAU 
                 plasminogen activator, urokinase 
                 NM_002658 
                 98 
               
               
                 DCP2 
                 decapping enzyme hDcp2 
                 NM_152624 
                 126 
               
               
                 SLC30A7 
                 solute carrier family 30 (zinc transporter), member 7 
                 NM_133496 
                 152 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Exacerbated Asthma three-fold increase 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 KRT24 
                 keratin 24 
                 NM_019016 
                 14 
               
               
                 SOSTDC1 
                 sclerostin domain containing 1 
                 NM_015464 
                 15 
               
               
                 BM039 
                 uncharacterized bone marrow protein BM039 
                 NM_018455 
                 16 
               
               
                 KRT6A 
                 keratin 6A 
                 NM_005554 
                 17 
               
               
                 CALB1 
                 calbindin 1, 28 kDa 
                 NM_004929 
                 18 
               
               
                 GPR65 
                 G protein-coupled receptor 65 
                 NM_003608 
                 20 
               
               
                 FPRL1 
                 formyl peptide receptor-like 1 
                 NM_001462 
                 24 
               
               
                 PROK2 
                 prokineticin 2 
                 NM_021935 
                 26 
               
               
                 PDE4B 
                 phosphodiesterase 4B, cAMP-specific (phosphodiesterase 
                 NM_002600 
                 27 
               
               
                   
                 E4 dunce homolog,  Drosophila ) 
                   
                   
               
               
                 FOS 
                 v-fos FBJ murine osteosarcoma viral oncogene homolog 
                 NM_005252 
                 28 
               
               
                 TREM1 
                 triggering receptor expressed on myeloid cells 1 
                 NM_018643 
                 29 
               
               
                 HAL 
                 histidine ammonia-lyase 
                 NM_002108 
                 30 
               
               
                 SLC2A14 
                 solute carrier family 2 (facilitated glucose transporter), 
                 NM_153449 
                 32 
               
               
                   
                 member 14 
                   
                   
               
               
                 AQP9 
                 aquaporin 9 
                 NM_020980 
                 33 
               
               
                 BCL2A1 
                 BCL2-related protein A1 
                 NM_004049 
                 34 
               
               
                 CYP1A1 
                 cytochrome P450, family 1, subfamily A, polypeptide 1 
                 NM_000499 
                 35 
               
               
                 SERPINB4 
                 serine (or cysteine) proteinase inhibitor, clade B 
                 NM_002974 
                 36 
               
               
                   
                 (ovalbumin), member 4 
                   
                   
               
               
                 CLECSF6 
                 C-type (calcium dependent, carbohydrate-recognition 
                 NM_016184 
                 40 
               
               
                   
                 domain) lectin, superfamily member 6 
                   
                   
               
               
                 IL1B 
                 interleukin 1, beta 
                 NM_000576 
                 41 
               
               
                 LILRB1 
                 leukocyte immunoglobulin-like receptor, subfamily B 
                 NM_D06669 
                 42 
               
               
                   
                 (with TM and ITIM domains), member 1 
                   
                   
               
               
                 SLC2A3 
                 solute carrier family 2 (facilitated glucose transporter), 
                 NM_006931 
                 43 
               
               
                   
                 member 3 
                   
                   
               
               
                 S100A9 
                 S100 calcium binding protein A9 (calgranulin B) 
                 NM_002965 
                 44 
               
               
                 PLEK 
                 pleckstrin 
                 NM_002664 
                 45 
               
               
                 DTNA 
                 dystrobrevin, alpha 
                 NM_001390 
                 47 
               
               
                 ARNTL2 
                 aryl hydrocarbon receptor nuclear translocator-like 2 
                 NM_020183 
                 48 
               
               
                 RAI3 
                 retinoic acid induced 3 
                 NM_003979 
                 49 
               
               
                 G0S2 
                 putative lymphocyte G0/G1 switch gene 
                 NM_015714 
                 50 
               
               
                 RPEL1 
                 RPEL repeat containing 1 
                 AB051520 
                 51 
               
               
                 CSF2RB 
                 colony stimulating factor 2 receptor, beta, low-affinity 
                 NM_000395 
                 52 
               
               
                   
                 (granulocyte-macrophage) 
                   
                   
               
               
                 PLAUR 
                 plasminogen activator, urokinase receptor 
                 NM_002659 
                 53 
               
               
                 HIST1H2BH 
                 histone 1, H2bh 
                 NM_003524 
                 54 
               
               
                 EMP1 
                 epithelial membrane protein 1 
                 NM_001423 
                 55 
               
               
                 TF 
                 transferrin 
                 NM_001063 
                 56 
               
               
                 PRG1 
                 proteoglycan 1, secretory granule 
                 NM_002727 
                 57 
               
               
                   
                 unnamed protein product; diaminopimelate 
                   
                   
               
               
                   
                 decarboxylase (AA 1-327);  Bacillus subtilis  lys gene for 
                 X17013 
                 58 
               
               
                   
                 diaminopimelate decarboxylase (EC 4.1.1.20). 
                   
                   
               
               
                 PLEK 
                 pleckstrin 
                 NM_002664 
                 59 
               
               
                 GPR43 
                 G protein-coupled receptor 43 
                 NM_005306 
                 60 
               
               
                 HIST1H2BC 
                 histone 1, H2bc 
                 NM_003526 
                 61 
               
               
                 SPRR1A 
                 small proline-rich protein 1A 
                 NM_005987 
                 62 
               
               
                   
                 integrin, alpha M (complement component receptor 3, 
                 NM_000632 
                 65 
               
               
                 ITGAM 
                 alpha; also known as CD11b (p170), macrophage antigen 
                   
                   
               
               
                   
                 alpha polypeptide) 
                   
                   
               
               
                 SOD2 
                 superoxide dismutase 2, mitochondrial 
                 NM_000636 
                 67 
               
               
                 GPR97 
                 G protein-coupled receptor 97 
                 NM_170776 
                 70 
               
               
                 SPEC1 
                 small protein effector 1 of Cdc42 
                 NM_020239 
                 72 
               
               
                 MMP25 
                 matrix metalloproteinase 25 
                 NM_022468 
                 73 
               
               
                   
                 synonyms: HIS, HSI, ARL1, ARL-1, ALDRLn, AKR1B11, 
                   
                   
               
               
                   
                 AKR1B12, MGC14103; aldose reductase-like 1; aldo-keto 
                   
                   
               
               
                 AKR1B10 
                 reductase family 1, member B11 (aldose reductase-like); 
                 NM_004812 
                 74 
               
               
                   
                 aldose reductase-like peptide; aldose reductase-related 
                   
                   
               
               
                   
                 protein; small intestine reductase; go —   
                   
                   
               
               
                   
                 synonyms: HIS, HSI, ARL1, ARL-1, ALDRLn, AKR1B11, 
                   
                   
               
               
                   
                 AKR1B12, MGC14103; aldose reductase-like 1; aldo-keto 
                   
                   
               
               
                 AKR1B10 
                 reductase family 1, member B11 (aldose reductase-like); 
                 NM_020299 
                 75 
               
               
                   
                 aldose reductase-like peptide; aldose reductase-related 
                   
                   
               
               
                   
                 protein; small intestine reductase; go —   
                   
                   
               
               
                 EMP1 
                 epithelial membrane protein 1 
                 NM_001423 
                 76 
               
               
                 HM74 
                 putative chemokine receptor 
                 NM_006018 
                 78 
               
               
                 NR4A1 
                 nuclear receptor subfamily 4, group A, member 1 
                 NM_002135 
                 79 
               
               
                 HIST1H1C 
                 histone 1, H1c 
                 NM_005319 
                 83 
               
               
                   
                   Homo sapiens  transcribed sequences 
                 BQ010718 
                 84 
               
               
                 SERPINB13 
                 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 13 
                 NM_012397 
                 86 
               
               
                 HIST1H2BK 
                 histone 1, H2bk 
                 NM_080593 
                 88 
               
               
                 IL1R2 
                 interleukin 1 receptor, type II 
                 NM_004633 
                 90 
               
               
                 DUSP5 
                 dual specificity phosphatase 5 
                 NM_004419 
                 92 
               
               
                 TLR4 
                 toll-like receptor 4 
                 NM_003266 
                 93 
               
               
                 CCR1 
                 chemokine (C—C motif) receptor 1 
                 NM_001295 
                 94 
               
               
                 RAI3 
                 retinoic acid induced 3 
                 NM_003979 
                 96 
               
               
                 KRT13 
                 keratin 13 
                 NM_153490 
                 97 
               
               
                   
                   Homo sapiens  transcribed sequences 
                 BQ277484 
                 101 
               
               
                 SLC11A1 
                 solute carrier family 11 (proton-coupled divalent metal 
                 NM_000578 
                 105 
               
               
                   
                 ion transporters), member 1 
                   
                   
               
               
                 C1QR1 
                 complement component 1, q subcomponent, receptor 1 
                 NM_012072 
                 106 
               
               
                 IL1A 
                 interleukin 1, alpha 
                 NM_000575 
                 107 
               
               
                 SPRR2B 
                 small proline-rich protein 2B 
                 NM_001017418 
                 109 
               
               
                 SPRR3 
                 small proline-rich protein 3 
                 NM_005416 
                 110 
               
               
                 MAD 
                 MAX dimerization protein 1 
                 NM_002357 
                 112 
               
               
                 CLECSF12 
                 C-type (calcium dependent, carbohydrate-recognition 
                 NM_197953 
                 114 
               
               
                   
                 domain) lectin, super-family member 12 
                   
                   
               
               
                 SPRR1B 
                 small proline-rich protein 1B (cornifin) 
                 NM_003125 
                 117 
               
               
                 EAT2 
                 SH2 domain-containing molecule EAT2 
                 NM_053282 
                 120 
               
               
                 PRV1 
                 polycythemia rubra vera 1 
                 NM_020406 
                 129 
               
               
                 RAB35 
                 RAB35, member RAS oncogene family 
                 NM_006861 
                 132 
               
               
                 S100A2 
                 S100 calcium binding protein A2 
                 NM_005978 
                 134 
               
               
                 CD44 
                 CD44 antigen (homing function and Indian blood group 
                 NM_000610 
                 135 
               
               
                   
                 system) 
                   
                   
               
               
                 JUNB 
                 jun B proto-oncogene 
                 NM_002229 
                 139 
               
               
                 LILRB2 
                 leukocyte immunoglobulin-like receptor, subfamily B 
                 NM_005874 
                 145 
               
               
                   
                 (with TM and ITIM domains), member 2 
                   
                   
               
               
                 C4.4A 
                 GPI-anchored metastasis-associated protein homolog 
                 NM_014400 
                 146 
               
               
                 CPA4 
                 carboxypeptidase A4 
                 NM_016352 
                 153 
               
               
                 LILRB1 
                 leukocyte immunoglobulin-like receptor, subfamily B 
                 NM_006669 
                 160 
               
               
                   
                 (with TM and ITIM domains), member 1 
                   
                   
               
               
                 FCGR2A 
                 Fc fragment of IgG, low affinity IIa, receptor for (CD32) 
                 NM_021642 
                 163 
               
               
                   
               
               
                 * Denotes a “corrected” accession number found in Genbank 
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Exacerbated Asthma two-fold decrease 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 SF1 
                 splicing factor 1 
                 NM_004630 
                 11 
               
               
                 KCTD7 
                 potassium channel tetramerisation domain containing 7 
                 NM_153033 
                 12 
               
               
                 DNAH7 
                 dynein, axonemal, heavy polypeptide 7 
                 NM_018897 
                 63 
               
               
                 FLJ23505 
                   Homo sapiens  cDNA: FLJ23505 fis, clone LNG03017 
                 NM_024716 
                 68 
               
               
                 KIF3A 
                 kinesin family member 3A 
                 NM_007054 
                 80 
               
               
                 IGFBP7 
                 insulin-like growth factor binding protein 7 
                 NM_001553 
                 81 
               
               
                 TSAP6 
                 tumor suppressor pHyde;  Homo sapiens  dudulin 2 
                 NM_182915 
                 82 
               
               
                   
                 (TSAP6), mRNA. 
                   
                   
               
               
                 IPW 
                   Homo sapiens  mRNA; cDNA DKFZp686M12165 (from 
                 BX648788 
                 89 
               
               
                   
                 clone DKFZp686M12165) 
                   
                   
               
               
                 PLTP 
                 phospholipid transfer protein 
                 NM_006227 
                 91 
               
               
                   
                 gb: BC029442.1/DB_XREF = gi: 20809535/TID = Hs2Affx.1.373/ 
                   
                   
               
               
                   
                 CNT = 1/FEA = FLmRNA/TIER = FL/STK = 1/ 
                   
                   
               
               
                   
                 NOTE = sequence(s) not in UniGene/DEF =  Homo sapiens , 
                 BC029442 
                 99 
               
               
                   
                 Similar to immunity associated protein 1, clone MGC: 32707 
                   
                   
               
               
                   
                 IMAGE: 4618467, mRNA, complete cds./PROD = Similar to immu 
                   
                   
               
               
                 SIAH1 
                 seven in absentia homolog 1 ( Drosophila ) 
                 NM_003031 
                 100 
               
               
                   
                   Homo sapiens  transcribed sequences 
                 BX107340 
                 103 
               
               
                 FLJ40427 
                 hypothetical protein FLJ40427 
                 NM_178504 
                 108 
               
               
                 DNAH5 
                 dynein, axonemal, heavy polypeptide 5 
                 NM_001369 
                 115 
               
               
                 DNAH9 
                 dynein, axonemal, heavy polypeptide 9 
                 NM_001372 
                 116 
               
               
                   
                   Homo sapiens  cDNA FLJ12411 fis, clone MAMMA1002964. 
                 AK022473 
                 118 
               
               
                 LOC123872 
                 similar to RIKEN cDNA 4930457P18 
                 NM_178452 
                 121 
               
               
                 CHST5 
                 carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 5 
                 NM_024533 
                 122 
               
               
                   
                 UI-H-BW0-aim-d-12-0-UI.s1 NCI_CGAP_Sub6  Homo   
                 AW294722 
                 123 
               
               
                   
                   sapiens  cDNA clone IMAGE: 2729902 3′, mRNA sequence. 
                   
                   
               
               
                 KIAA1688 
                 KIAA1688 protein 
                 AB051475 
                 125 
               
               
                 DCDC2 
                 doublecortin domain containing 2 
                 NM_016356 
                 127 
               
               
                   
                   Homo sapiens  transcribed sequences 
                 CD698727 
                 128 
               
               
                 SPAG8 
                 sperm associated antigen 8 
                 NM_012436 
                 130 
               
               
                 ATM 
                 ataxia telangiectasia mutated (includes complementation 
                 NM_000051 
                 138 
               
               
                   
                 groups A, C and D) 
                   
                   
               
               
                 FLJ13621 
                 hypothetical protein FLJ13621 
                 NM_025009 
                 140 
               
               
                 HPX 
                 hemopexin 
                 NM_000613 
                 141 
               
               
                 DNAI2 
                 dynein, axonemal, intermediate polypeptide 2 
                 NM_023036 
                 143 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp761D2417 (from clone 
                 AL831856 
                 148 
               
               
                   
                 DKFZp761D2417) 
                   
                 148 
               
               
                 MGC16202 
                 hypothetical protein MGC16202 
                 NM_032373 
                 156 
               
               
                   
                   Homo sapiens  LOH11CR1P gene, loss of heterozygosity, 
                 CA428747 
                 157 
               
               
                   
                 11, chromosomal region 1 gene P product 
                   
                   
               
               
                 LOC146177 
                   Homo sapiens  hypothetical protein LOC146177 
                 NM_175059 
                 158 
               
               
                   
                 (LOC146177), mRNA. 
                   
                   
               
               
                 MGC40053 
                 hypothetical protein MGC40053 
                 NM_152583 
                 161 
               
               
                 LOC339005 
                   Homo sapiens  cDNA FLJ33935 fis, clone CTONG2017910. 
                 AK091254 
                 162 
               
               
                   
                 alternatively spliced; beta-1 form; possible membrane- 
                   
                   
               
               
                 C18orf1 
                 spanning protein; clone 22;  Homo sapiens  chromosome 
                 NM_181481 
                 164 
               
               
                   
                 18 open reading frame 1 (C18orf1), mRNA. 
                   
                   
               
               
                 MYEF2 
                 myelin expression factor 2 
                 NM_016132 
                 165 
               
               
                 DNAH3 
                 dynein, axonemal, heavy polypeptide 3 
                 NM_017539 
                 167 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Exacerbated Asthma three-fold decrease 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 CLGN 
                 calmegin 
                 NM_004362 
                 13 
               
               
                 ADCY2 
                 adenylate cyclase 2 (brain) 
                 NM_020546 
                 46 
               
               
                   
                   Homo sapiens  transcribed sequence with weak similarity 
                   
                   
               
               
                   
                 to protein sp: P39194 ( H. sapiens ) ALU7_HUMAN Alu 
                 BX361062 
                 66 
               
               
                   
                 subfamily SQ sequence contamination warning entry 
                   
                   
               
               
                 MGC26733 
                 hypothetical protein MGC26733 
                 NM_144992 
                 104 
               
               
                 MYLK 
                 myosin, light polypeptide kinase 
                 NM_053025 
                 111 
               
               
                 SLC26A7 
                 solute carrier family 26, member 7 
                 NM_052832 
                 119 
               
               
                   
                   Homo sapiens  cDNA: FLJ22631 fis, clone HSI06451. 
                 AK026284 
                 124 
               
               
                 LOC138428 
                 hypothetical protein LOC286207 
                 AL833241 
                 133 
               
               
                   
                   Homo sapiens  cDNA: FLJ22781 fis, clone KAIA1958. 
                 AK026434 
                 136 
               
               
                   
                   Homo sapiens  cDNA FLJ12093 fis, clone HEMBB1002603. 
                 AK022155 
                 137 
               
               
                   
                   Homo sapiens  cDNA: FLJ23502 fis, clone LNG02862 
                 AK027155 
                 142 
               
               
                 LOC165186 
                 UI-H-EZ1-bbk-j-02-0-UI.s1 NCI_CGAP_Ch2  Homo   
                 NM_199280 
                 144 
               
               
                   
                   sapiens  cDNA clone UI-H-EZ1-bbk-j-02-0-UI 3′, mRNA 
                   
                   
               
               
                   
                 sequence.; ESTs, Weakly similar to T00057 hypothetical 
                   
                   
               
               
                   
                 protein KIAA0423 - human (fragment) [ H. sapiens ] 
                   
                   
               
               
                   
                 UI-E-EJ0-ahi-c-20-0-UI.r1 UI-E-EJ0  Homo sapiens  cDNA 
                 BM712946 
                 149 
               
               
                   
                 clone UI-E-EJ0-ahi-c-20-0-UI 5′, mRNA sequence. 
                   
                   
               
               
                 FLJ14665 
                 Start codon is not identified.;  Homo sapiens  mRNA for 
                 AB058767 
                 155 
               
               
                   
                 KIAA1864 protein, partial cds. 
                   
                   
               
               
                 SCARF2 
                 scavenger receptor class F, member 2 
                 NM_153334 
                 159 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Stable Asthma two-fold increase 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 SOSTDC1 
                 sclerostin domain containing 1 
                 NM_015464 
                 15 
               
               
                 BM039 
                 uncharacterized bone marrow protein BM039 
                 NM_018455 
                 16 
               
               
                 CALB1 
                 calbindin 1, 28 kDa 
                 NM_004929 
                 18 
               
               
                 CYP1A1 
                 cytochrome P450, family 1, subfamily A, polypeptide 1 
                 NM_000499 
                 35 
               
               
                   
                   Homo sapiens  transcribed sequences 
                 AI476722 
                 37 
               
               
                 EMP1 
                 epithelial membrane protein 1 
                 NM_001423 
                 76 
               
               
                 SCEL 
                 sciellin 
                 NM_144777 
                 77 
               
               
                   
                 UI-H-BW0-aim-d-12-0-UI.s1 NCI_CGAP_Sub6  Homo   
                 AW294722 
                 123 
               
               
                   
                   sapiens  cDNA clone IMAGE: 2729902 3′, mRNA sequence. 
                   
                   
               
               
                 DCP2 
                 decapping enzyme hDcp2 
                 NM_152624 
                 126 
               
               
                 RAB35 
                 RAB35, member RAS oncogene family 
                 NM_006861 
                 132 
               
               
                 SLC30A7 
                 solute carrier family 30 (zinc transporter), member 7 
                 NM_133496 
                 152 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Stable Asthma three-fold increase 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 FOS 
                 v-fos FBJ murine osteosarcoma viral oncogene homolog 
                 NM_005252 
                 28 
               
               
                 ZNF407 
                 zinc finger protein 407 
                 NM_017757 
                 31 
               
               
                 ZCCHC2 
                 zinc finger, CCHC domain containing 2 
                 NM_017742 
                 38 
               
               
                 ARNTL2 
                 aryl hydrocarbon receptor nuclear translocator-like 2 
                 NM_020183 
                 48 
               
               
                   
                 unnamed protein product; diaminopimelate decarboxylase 
                   
                   
               
               
                   
                 (AA 1-327);  Bacillus subtilis  lys gene for diaminopimelate 
                 X17013 
                 58 
               
               
                   
                 decarboxylase (EC 4.1.1.20). 
                   
                   
               
               
                 SPEC1 
                 small protein effector 1 of Cdc42 
                 NM_020239 
                 72 
               
               
                   
                   Homo sapiens  transcribed sequences 
                 BQ277484 
                 101 
               
               
                 CBX5 
                 chromobox homolog 5 (HP1 alpha homolog,  Drosophila ) 
                 NM_012117 
                 131 
               
               
                 C4.4A 
                 GPI-anchored metastasis-associated protein homolog 
                 NM_014400 
                 146 
               
               
                 FLJ10525 
                 hypothetical protein FLJ10525 
                 NM_018126 
                 154 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Stable Asthma two-fold decrease 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 BCL6 
                 B-cell CLL/lymphoma 6 (zinc finger protein 51) 
                 NM_138931 
                 21 
               
               
                 TREM1 
                 triggering receptor expressed on myeloid cells 1 
                 NM_018643 
                 29 
               
               
                 RPEL1 
                 RPEL repeat containing 1 
                 AB051520 
                 51 
               
               
                 DNCI1 
                 dynein, cytoplasmic, intermediate polypeptide 1 
                 NM_004411 
                 85 
               
               
                 EPOR 
                 erythropoietin receptor 
                 NM_000121 
                 87 
               
               
                 LILRB2 
                 leukocyte immunoglobulin-like receptor, subfamily B 
                 NM_005874 
                 145 
               
               
                   
                 (with TM and ITIM domains), member 2 
                   
                   
               
               
                 HLA-DPB1 
                 major histocompatibility complex, class II, DP beta 1 
                 NM_002121 
                 147 
               
               
                 KCNC3 
                 potassium voltage-gated channel, Shaw-related subfamily, 
                 NM_004977 
                 166 
               
               
                   
                 member 3 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Stable Asthma three-fold decrease 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp566D053 (from 
                 AW611486 
                 71 
               
               
                   
                 clone DKFZp566D053) 
                   
                   
               
               
                 LOC253559 
                 nectin-like protein 3 
                 NM_153184 
                 95 
               
               
                 ZNF483 
                 zinc finger protein 483 
                 NM_007169 
                 150 
               
               
                 ZNF483 
                 zinc finger protein 483 
                 NM_133464 
                 151 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 9 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Exacerbated Asthma increases, Stable Asthma no change 
               
             
          
           
               
                 Common 
                 Description 
                 Genbank 
                 Seq. ID Number 
               
               
                   
               
             
          
           
               
                 KRT24 
                 keratin 24 
                 NM_019016 
                 14 
               
               
                 KRT6A 
                 keratin 6A 
                 NM_005554 
                 17 
               
               
                 GPR65 
                 G protein-coupled receptor 65 
                 NM_003608 
                 20 
               
               
                 EMR2 
                 egf-like module containing, mucin-like, hormone receptor- 
                 NM_013447 
                 22 
               
               
                   
                 like 2 
                   
                   
               
               
                 THBD 
                 thrombomodulin 
                 NM_000361 
                 23 
               
               
                 FPRL1 
                 formyl peptide receptor-like 1 
                 NM_001462 
                 24 
               
               
                 PROK2 
                 prokineticin 2 
                 NM_021935 
                 26 
               
               
                 PDE4B 
                 phosphodiesterase 4B, cAMP-specific (phosphodiesterase 
                 NM_002600 
                 27 
               
               
                   
                 E4 dunce homolog,  Drosophila ) 
                   
                   
               
               
                 HAL 
                 histidine ammonia-lyase 
                 NM_002108 
                 30 
               
               
                 SLC2A14 
                 solute carrier family 2 (facilitated glucose transporter), 
                 NM_153449 
                 32 
               
               
                   
                 member 14 
                   
                   
               
               
                 AQP9 
                 aquaporin 9 
                 NM_020980 
                 33 
               
               
                 BCL2A1 
                 BCL2-related protein A1 
                 NM_004049 
                 34 
               
               
                 SERPINB4 
                 serine (or cysteine) proteinase inhibitor, clade B 
                 NM_002974 
                 36 
               
               
                   
                 (ovalbumin), member 4 
                   
                   
               
               
                 ALDH1A3 
                 aldehyde dehydrogenase 1 family, member A3 
                 NM_000693 
                 39 
               
               
                 CLECSF6 
                 C-type (calcium dependent, carbohydrate-recognition 
                 NM_016184 
                 40 
               
               
                   
                 domain) lectin, superfamily member 6 
                   
                   
               
               
                 IL1B 
                 interleukin 1, beta 
                 NM_000576 
                 41 
               
               
                 LILRB1 
                 leukocyte immunoglobulin-like receptor, subfamily B (with 
                 NM_006669 
                 42 
               
               
                   
                 TM and ITIM domains), member 1 
                   
                   
               
               
                 SLC2A3 
                 solute carrier family 2 (facilitated glucose transporter), 
                 NM_006931 
                 43 
               
               
                   
                 member 3 
                   
                   
               
               
                 S100A9 
                 S100 calcium binding protein A9 (calgranulin B) 
                 NM_002965 
                 44 
               
               
                 PLEK 
                 pleckstrin 
                 NM_002664 
                 45 
               
               
                 DTNA 
                 dystrobrevin, alpha 
                 NM_001390 
                 47 
               
               
                 RAI3 
                 retinoic acid induced 3 
                 NM_003979 
                 49 
               
               
                 G0S2 
                 putative lymphocyte G0/G1 switch gene 
                 NM_015714 
                 50 
               
               
                 CSF2RB 
                 colony stimulating factor 2 receptor, beta, low-affinity 
                 NM_000395 
                 52 
               
               
                   
                 (granulocyte-macrophage) 
                   
                   
               
               
                 PLAUR 
                 plasminogen activator, urokinase receptor 
                 NM_002659 
                 53 
               
               
                 HIST1H2BH 
                 histone 1, H2bh 
                 NM_003524 
                 54 
               
               
                 EMP1 
                 epithelial membrane protein 1 
                 NM_001423 
                 55 
               
               
                 TF 
                 transferrin 
                 NM_001063 
                 56 
               
               
                 PRG1 
                 proteoglycan 1, secretory granule 
                 NM_002727 
                 57 
               
               
                 PLEK 
                 pleckstrin 
                 NM_002664 
                 59 
               
               
                 GPR43 
                 G protein-coupled receptor 43 
                 NM_005306 
                 60 
               
               
                 HIST1H2BC 
                 histone 1, H2bc 
                 NM_003526 
                 61 
               
               
                 SPRR1A 
                 small proline-rich protein 1A 
                 NM_005987 
                 62 
               
               
                   
                 integrin, alpha M (complement component receptor 3, 
                   
                   
               
               
                 ITGAM 
                 alpha; also known as CD11b (p170), macrophage antigen 
                 NM_000632 
                 65 
               
               
                   
                 alpha polypeptide) 
                   
                   
               
               
                 SOD2 
                 superoxide dismutase 2, mitochondrial 
                 NM_000636 
                 67 
               
               
                 OLR1 
                 oxidised low density lipoprotein (lectin-like) receptor 1 
                 NM_002543 
                 69 
               
               
                 GPR97 
                 G protein-coupled receptor 97 
                 NM_170776 
                 70 
               
               
                 MMP25 
                 matrix metalloproteinase 25 
                 NM_022468 
                 73 
               
               
                   
                 synonyms: HIS, HSI, ARL1, ARL-1, ALDRLn, AKR1B11, 
                 NM_004812 
                 74 
               
               
                   
                 AKR1B12, MGC14103; aldose reductase-like 1; aldo-keto 
                   
                   
               
               
                 AKR1B10 
                 reductase family 1, member B11 (aldose reductase-like); 
                 NM_020299* 
                   
               
               
                   
                 aldose reductase-like peptide; aldose reductase-related 
                   
                   
               
               
                   
                 protein; small intestine reductase; go —   
                   
                   
               
               
                   
                 synonyms: HIS, HSI, ARL1, ARL-1, ALDRLn, AKR1B11, 
                   
                   
               
               
                   
                 AKR1B12, MGC14103; aldose reductase-like 1; aldo-keto 
                   
                   
               
               
                 AKR1B10 
                 reductase family 1, member B11 (aldose reductase-like); 
                 NM_020299 
                 75 
               
               
                   
                 aldose reductase-like peptide; aldose reductase-related 
                   
                   
               
               
                   
                 protein; small intestine reductase; go —   
                   
                   
               
               
                 HM74 
                 putative chemokine receptor 
                 NM_006018 
                 78 
               
               
                 NR4A1 
                 nuclear receptor subfamily 4, group A, member 1 
                 NM_002135 
                 79 
               
               
                 HIST1H1C 
                 histone 1, H1c 
                 NM_005319 
                 83 
               
               
                   
                   Homo sapiens  transcribed sequences 
                 BQ010718 
                 84 
               
               
                 SERPINB13 
                 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 13 
                 NM_012397 
                 86 
               
               
                 HIST1H2BK 
                 histone 1, H2bk 
                 NM_080593 
                 88 
               
               
                 IL1R2 
                 interleukin 1 receptor, type II 
                 NM_004633 
                 90 
               
               
                 DUSP5 
                 dual specificity phosphatase 5 
                 NM_004419 
                 92 
               
               
                 TLR4 
                 toll-like receptor 4 
                 NM_003266 
                 93 
               
               
                 CCR1 
                 chemokine (C—C motif) receptor 1 
                 NM_001295 
                 94 
               
               
                 RAI3 
                 retinoic acid induced 3 
                 NM_003979 
                 96 
               
               
                 KRT13 
                 keratin 13 
                 NM_153490 
                 97 
               
               
                 PLAU 
                 plasminogen activator, urokinase 
                 NM_002658 
                 98 
               
               
                 SLC11A1 
                 solute carrier family 11 (proton-coupled divalent metal ion transporters), member 1 
                 NM_000578 
                 105 
               
               
                 C1QR1 
                 complement component 1, q subcomponent, receptor 1 
                 NM_012072 
                 106 
               
               
                 IL1A 
                 interleukin 1, alpha 
                 NM_000575 
                 107 
               
               
                 SPRR2B 
                 small proline-rich protein 2B 
                 NM_001017418 
                 109 
               
               
                 SPRR3 
                 small proline-rich protein 3 
                 NM_005416 
                 110 
               
               
                 MAD 
                 MAX dimerization protein 1 
                 NM_002357 
                 112 
               
               
                 CLECSF12 
                 C-type (calcium dependent, carbohydrate-recognition 
                 NM_197953 
                 114 
               
               
                   
                 domain) lectin, super-family member 12 
                   
                   
               
               
                 SPRR1B 
                 small proline-rich protein 1B (cornifin) 
                 NM_003125 
                 117 
               
               
                 EAT2 
                 SH2 domain-containing molecule EAT2 
                 NM_053282 
                 120 
               
               
                 PRV1 
                 polycythemia rubra vera 1 
                 NM_020406 
                 129 
               
               
                 S100A2 
                 S100 calcium binding protein A2 
                 NM_005978 
                 134 
               
               
                 CD44 
                 CD44 antigen (homing function and Indian blood group 
                 NM_000610 
                 135 
               
               
                   
                 system) 
                   
                   
               
               
                 JUNB 
                 jun B proto-oncogene 
                 NM_002229 
                 139 
               
               
                 LILRB2 
                 leukocyte immunoglobulin-like receptor, subfamily B (with 
                 NM_005874 
                 145 
               
               
                   
                 TM and ITIM domains), member 2 
                   
                   
               
               
                 CPA4 
                 carboxypeptidase A4 
                 NM_016352 
                 153 
               
               
                 LILRB1 
                 leukocyte immunoglobulin-like receptor, subfamily B (with 
                 NM_006669 
                 160 
               
               
                   
                 TM and ITIM domains), member 1 
                   
                   
               
               
                 FCGR2A 
                 Fc fragment of IgG, low affinity IIa, receptor for (CD32) 
                 NM_021642 
                 163 
               
               
                   
               
               
                 *corrected accession number in Genbank 
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 10 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Exacerbated Asthma decreases, Stable Asthma no change 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 SF1 
                 splicing factor 1 
                 NM_004630 
                 11 
               
               
                 KCTD7 
                 potassium channel tetramerisation domain containing 7 
                 NM_153033 
                 12 
               
               
                 CLGN 
                 calmegin 
                 NM_004362 
                 13 
               
               
                 ADCY2 
                 adenylate cyclase 2 (brain) 
                 NM_020546 
                 46 
               
               
                 DNAH7 
                 dynein, axonemal, heavy polypeptide 7 
                 NM_018897 
                 63 
               
               
                   
                   Homo sapiens  transcribed sequence with weak similarity to 
                   
                   
               
               
                   
                 protein sp: P39194 ( H. sapiens ) ALU7_HUMAN Alu subfamily 
                 BX361062 
                 66 
               
               
                   
                 SQ sequence contamination warning entry 
                   
                   
               
               
                 FLJ23505 
                   Homo sapiens  cDNA: FLJ23505 fis, clone LNG03017 
                 NM_024716 
                 68 
               
               
                 KIF3A 
                 kinesin family member 3A 
                 NM_007054 
                 80 
               
               
                 IGFBP7 
                 insulin-like growth factor binding protein 7 
                 NM_001553 
                 81 
               
               
                 TSAP6 
                 tumor suppressor pHyde;  Homo sapiens  dudulin 2 (TSAP6), 
                 NM_182915 
                 82 
               
               
                   
                 mRNA. 
                   
                   
               
               
                 IPW 
                   Homo sapiens  mRNA; cDNA DKFZp686M12165 (from clone 
                 BX648788 
                 89 
               
               
                   
                 DKFZp686M12165) 
                   
                   
               
               
                 PLTP 
                 phospholipid transfer protein 
                 NM_006227 
                 91 
               
               
                   
                 gb: BC029442.1/DB_XREF = gi: 20809535/TID = Hs2Affx.1.373/ 
                   
                   
               
               
                   
                 CNT = 1/FEA = FLmRNA/TIER = FL/STK = 1/ 
                   
                   
               
               
                   
                 NOTE = sequence(s) not in UniGene/DEF =  Homo sapiens , 
                 BC029442 
                 99 
               
               
                   
                 Similar to immunity associated protein 1, clone MGC: 32707 
                   
                   
               
               
                   
                 IMAGE: 4618467, mRNA, complete cds./PROD = Similar to immu 
                   
                   
               
               
                 SIAH1 
                 seven in absentia homolog 1 ( Drosophila ) 
                 NM_003031 
                 100 
               
               
                   
                   Homo sapiens  transcribed sequences 
                 BX107340 
                 103 
               
               
                 MGC26733 
                 hypothetical protein MGC26733 
                 NM_144992 
                 104 
               
               
                 FLJ40427 
                 hypothetical protein FLJ40427 
                 NM_178504 
                 108 
               
               
                 MYLK 
                 myosin, light polypeptide kinase 
                 NM_053025 
                 111 
               
               
                 DNAH5 
                 dynein, axonemal, heavy polypeptide 5 
                 NM_001369 
                 115 
               
               
                 DNAH9 
                 dynein, axonemal, heavy polypeptide 9 
                 NM_001372 
                 116 
               
               
                   
                   Homo sapiens  cDNA FLJ12411 fis, clone MAMMA1002964. 
                 AK022473 
                 118 
               
               
                 SLC26A7 
                 solute carrier family 26, member 7 
                 NM_052832 
                 119 
               
               
                 LOC123872 
                 similar to RIKEN cDNA 4930457P18 
                 NM_178452 
                 121 
               
               
                 CHST5 
                 carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 5 
                 NM_024533 
                 122 
               
               
                   
                   Homo sapiens  cDNA: FLJ22631 fis, clone HSI06451. 
                 AK026284 
                 124 
               
               
                 KIAA1688 
                 KIAA1688 protein 
                 AB051475 
                 125 
               
               
                 DCDC2 
                 doublecortin domain containing 2 
                 NM_016356 
                 127 
               
               
                   
                   Homo sapiens  transcribed sequences 
                 CD698727 
                 128 
               
               
                 SPAG8 
                 sperm associated antigen 8 
                 NM_012436 
                 130 
               
               
                 LOC138428 
                 hypothetical protein LOC286207 
                 AL833241 
                 133 
               
               
                   
                   Homo sapiens  cDNA: FLJ22781 fis, clone KAIA1958. 
                 AK026434 
                 136 
               
               
                   
                   Homo sapiens  cDNA FLJ12093 fis, clone HEMBB1002603. 
                 AK022155 
                 137 
               
               
                 ATM 
                 ataxia telangiectasia mutated (includes complementation 
                 NM_000051 
                 138 
               
               
                   
                 groups A, C and D) 
                   
                   
               
               
                 FLJ13621 
                 hypothetical protein FLJ13621 
                 NM_025009 
                 140 
               
               
                 HPX 
                 hemopexin 
                 NM_000613 
                 141 
               
               
                   
                   Homo sapiens  cDNA: FLJ23502 fis, clone LNG02862 
                 AK027155 
                 142 
               
               
                 DNAI2 
                 dynein, axonemal, intermediate polypeptide 2 
                 NM_023036 
                 143 
               
               
                   
                 UI-H-EZ1-bbk-j-02-0-UI.s1 NCI_CGAP_Ch2  Homo sapiens   
                   
                   
               
               
                 LOC165186 
                 cDNA clone UI-H-EZ1-bbk-j-02-0-UI 
                 NM_199280 
                 144 
               
               
                   
                 3′, mRNA sequence.; 
                   
                   
               
               
                   
                 ESTs, Weakly similar to T00057 hypothetical protein 
                   
                   
               
               
                   
                 KIAA0423 - human (fragment) [ H. sapiens ] 
                   
                   
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp761D2417 (from clone 
                   
                   
               
               
                   
                 DKFZp761D2417) 
                 AL831856 
                 148 
               
               
                   
                 UI-E-EJO-ahi-c-20-0-UI.r1 UI-E-EJO  Homo sapiens  cDNA 
                 BM712946 
                 149 
               
               
                   
                 clone UI-E-EJO-ahi-c-20-0-UI 5′, mRNA sequence. 
                   
                   
               
               
                 FLJ14665 
                 Start codon is not identified.;  Homo sapiens  mRNA for 
                 AB058767 
                 155 
               
               
                   
                 KIAA1864 protein, partial cds. 
                   
                   
               
               
                 MGC16202 
                 hypothetical protein MGC16202 
                 NM_032373 
                 156 
               
               
                   
                   Homo sapiens  LOH11CR1P gene, loss of heterozygosity, 11, 
                 CA478747 
                 157 
               
               
                   
                 chromosomal region 1 gene P product 
                   
                   
               
               
                 LOC146177 
                   Homo sapiens  hypothetical protein LOC146177 
                 NM_175059 
                 158 
               
               
                   
                 (LOC146177), mRNA. 
                   
                   
               
               
                 SCARF2 
                 scavenger receptor class F, member 2 
                 NM_153334 
                 159 
               
               
                 MGC40053 
                 hypothetical protein MGC40053 
                 NM_152583 
                 161 
               
               
                 LOC339005 
                   Homo sapiens  cDNA FLJ33935 fis, clone CTONG2017910. 
                 AK091254 
                 162 
               
               
                   
                 alternatively spliced; beta-1 form; possible membrane- 
                   
                   
               
               
                 C18orf1 
                 spanning protein; clone 22;  Homo sapiens  chromosome 18 
                 NM_181481 
                 164 
               
               
                   
                 open reading frame 1 (C18orf1), mRNA. 
                   
                   
               
               
                 MYEF2 
                 myelin expression factor 2 
                 NM_016132 
                 165 
               
               
                 DNAH3 
                 dynein, axonemal, heavy polypeptide 3 
                 NM_017539 
                 167 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 11 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Stable Asthma increases, Exacerbated Asthma no change 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                   
                   Homo sapiens  transcribed sequences 
                 AI476722 
                 37 
               
               
                 ZCCHC2 
                 zinc finger, CCHC domain containing 2 
                 NM_017742 
                 38 
               
               
                 CBX5 
                 chromobox homolog 5 (HP1 alpha homolog,  Drosophila ) 
                 NM_012117 
                 131 
               
               
                 FLJ10525 
                 hypothetical protein FLJ10525 
                 NM_018126 
                 154 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 12 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Stable Asthma decreases, Exacerbated Asthma no change 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 BCL6 
                 B-cell CLL/lymphoma 6 (zinc finger protein 51) 
                 NM_138931 
                 21 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp566D053 (from clone 
                 AW611486 
                 71 
               
               
                   
                 DKFZp566D053) 
                   
                   
               
               
                 DNCI1 
                 dynein, cytoplasmic, intermediate polypeptide 1 
                 NM_004411 
                 85 
               
               
                 EPOR 
                 erythropoietin receptor 
                 NM_000121 
                 87 
               
               
                 LOC253559 
                 nectin-like protein 3 
                 NM_153184 
                 95 
               
               
                 HLA-DPB1 
                 major histocompatibility complex, class II, DP beta 1 
                 NM_002121 
                 147 
               
               
                 ZNF483 
                 zinc finger protein 483 
                 NM_007169 
                 150 
               
               
                 ZNF483 
                 zinc finger protein 483 
                 NM_133464 
                 151 
               
               
                 KCNC3 
                 potassium voltage-gated channel, Shaw-related subfamily, 
                 NM_004977 
                 166 
               
               
                   
                 member 3 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 13 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Stable Asthma increases, Exacerbated Asthma increases 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 SOSTDC1 
                 sclerostin domain containing 1 
                 NM_015464 
                 15 
               
               
                 BM039 
                 uncharacterized bone marrow protein BM039 
                 NM_018455 
                 16 
               
               
                 CALB1 
                 calbindin 1, 28 kDa 
                 NM_004929 
                 18 
               
               
                 FOS 
                 v-fos FBJ murine osteosarcoma viral oncogene homolog 
                 NM_005252 
                 28 
               
               
                 ZNF407 
                 zinc finger protein 407 
                 NM_017757 
                 31 
               
               
                 CYP1A1 
                 cytochrome P450, family 1, subfamily A, polypeptide 1 
                 NM_000499 
                 35 
               
               
                 ARNTL2 
                 aryl hydrocarbon receptor nuclear translocator-like 2 
                 NM_020183 
                 48 
               
               
                   
                 unnamed protein product; diaminopimelate decarboxylase 
                   
                   
               
               
                   
                 (AA 1-327);  Bacillus subtilis  lys gene for diaminopimelate 
                 X17013 
                 58 
               
               
                   
                 decarboxylase (EC 4.1.1.20). 
                   
                   
               
               
                 SPEC1 
                 small protein effector 1 of Cdc42 
                 NM_020239 
                 72 
               
               
                 EMP1 
                 epithelial membrane protein 1 
                 NM_001423 
                 76 
               
               
                 SCEL 
                 sciellin 
                 NM_144777 
                 77 
               
               
                   
                   Homo sapiens  transcribed sequences 
                 BQ277484 
                 101 
               
               
                 DCP2 
                 decapping enzyme hDcp2 
                 NM_152624 
                 126 
               
               
                 RAB35 
                 RAB35, member RAS oncogene family 
                 NM_006861 
                 132 
               
               
                 C4.4A 
                 GPI-anchored metastasis-associated protein homolog 
                 NM_014400 
                 146 
               
               
                 SLC30A7 
                 solute carrier family 30 (zinc transporter), member 7 
                 NM_133496 
                 152 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 14 
               
             
             
               
                   
               
               
                 Individual samples 
               
               
                 Inverse Changes 
               
               
                 Stable Asthma increases, Exacerbated Asthma Decrease or Stable Asthma decreases, 
               
               
                 Exacerbated Asthma increases 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 TREM1 
                 triggering receptor expressed on myeloid cells 1 
                 NM_018643 
                 29 
               
               
                 RPEL1 
                 RPEL repeat containing 1 
                 AB051520 
                 51 
               
               
                   
                 UI-H-BW0-aim-d-12-0-UI.s1 NCI_CGAP_Sub6  Homo sapiens   
                 AW294722 
                 123 
               
               
                   
                 cDNA clone IMAGE: 2729902 3′, mRNA sequence. 
                   
                   
               
               
                 LILRB2 
                 leukocyte immunoglobulin-like receptor, subfamily B (with TM 
                 NM_005874 
                 145 
               
               
                   
                 and ITIM domains), member 2 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 15 
               
             
             
               
                   
               
               
                 Pooled samples 
               
               
                 Exacerbated Asthma two-fold increase 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
               
                 GPR65 
                 G protein-coupled receptor 65 
                 NM_003608 
                 20 
               
               
                 HAL 
                 histidine ammonia-lyase 
                 NM_002108 
                 30 
               
               
                 SLC2A14 
                 solute carrier family 2 (facilitated glucose transporter), 
                 NM_153449 
                 32 
               
               
                   
                 member 14 
                   
                   
               
               
                 PLAUR 
                 plasminogen activator, urokinase receptor 
                 NM_002659 
                 53 
               
               
                 TF 
                 transferrin 
                 NM_001063 
                 56 
               
               
                 PLEK 
                 pleckstrin 
                 NM_002664 
                 59 
               
               
                 HIST1H2BC 
                 histone 1, H2bc 
                 NM_003526 
                 61 
               
               
                 GPR97 
                 G protein-coupled receptor 97 
                 NM_170776 
                 70 
               
               
                 HIST1H2BK 
                 histone 1, H2bk 
                 NM_080593 
                 88 
               
               
                 IL1R2 
                 interleukin 1 receptor, type II 
                 NM_004633 
                 90 
               
               
                 DUSP5 
                 dual specificity phosphatase 5 
                 NM_004419 
                 92 
               
               
                 TLR4 
                 toll-like receptor 4 
                 NM_003266 
                 93 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 16 
               
             
             
               
                   
               
               
                 Pooled samples 
               
               
                 Exacerbated Asthma three-fold increase 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 KRT24 
                 keratin 24 
                 NM_019016 
                 14 
               
               
                 SOSTDC1 
                 sclerostin domain containing 1 
                 NM_015464 
                 15 
               
               
                 KRT6A 
                 keratin 6A 
                 NM_005554 
                 17 
               
               
                 CALB1 
                 calbindin 1, 28 kDa 
                 NM_004929 
                 18 
               
               
                 FCGR2B 
                 Fc fragment of IgG, low affinity IIb, receptor for (CD32) 
                 NM_004001 
                 19 
               
               
                 EMR2 
                 egf-like module containing, mucin-like, hormone receptor- 
                 NM_013447 
                 22 
               
               
                   
                 like 2 
                   
                   
               
               
                 FPRL1 
                 formyl peptide receptor-like 1 
                 NM_001462 
                 24 
               
               
                 PDE4B 
                 phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 
                 NM_002600 
                 27 
               
               
                   
                 dunce homolog,  Drosophila ) 
                   
                   
               
               
                 FOS 
                 v-fos FBJ murine osteosarcoma viral oncogene homolog 
                 NM_005252 
                 28 
               
               
                 TREM1 
                 triggering receptor expressed on myeloid cells 1 
                 NM_018643 
                 29 
               
               
                 ZNF407 
                 zinc finger protein 407 
                 NM_017757 
                 31 
               
               
                 AQP9 
                 aquaporin 9 
                 NM_020980 
                 33 
               
               
                 BCL2A1 
                 BCL2-related protein A1 
                 NM_004049 
                 34 
               
               
                 CYP1A1 
                 cytochrome P450, family 1, subfamily A, polypeptide 1 
                 NM_000499 
                 35 
               
               
                 ALDH1A3 
                 aldehyde dehydrogenase 1 family, member A3 
                 NM_000693 
                 39 
               
               
                 CLECSF6 
                 C-type (calcium dependent, carbohydrate-recognition 
                 NM_016184 
                 40 
               
               
                   
                 domain) lectin, superfamily member 6 
                   
                   
               
               
                 IL1B 
                 interleukin 1, beta 
                 NM_000576 
                 41 
               
               
                 LILRB1 
                 leukocyte immunoglobulin-like receptor, subfamily B (with 
                 NM_006669 
                 42 
               
               
                   
                 TM and ITIM domains), member 1 
                   
                   
               
               
                 SLC2A3 
                 solute carrier family 2 (facilitated glucose transporter), 
                 NM_006931 
                 43 
               
               
                   
                 member 3 
                   
                   
               
               
                 S100A9 
                 S100 calcium binding protein A9 (calgranulin B) 
                 NM_002965 
                 44 
               
               
                 PLEK 
                 pleckstrin 
                 NM_002664 
                 45 
               
               
                 DTNA 
                 dystrobrevin, alpha 
                 NM_001390 
                 47 
               
               
                 RAI3 
                 retinoic acid induced 3 
                 NM_003979 
                 49 
               
               
                 G0S2 
                 putative lymphocyte G0/G1 switch gene 
                 NM_015714 
                 50 
               
               
                 RPEL1 
                 RPEL repeat containing 1 
                 AB051520 
                 51 
               
               
                 CSF2RB 
                 colony stimulating factor 2 receptor, beta, low-affinity 
                 NM_000395 
                 52 
               
               
                   
                 (granulocyte-macrophage) 
                   
                   
               
               
                 EMP1 
                 epithelial membrane protein 1 
                 NM_001423 
                 55 
               
               
                 PRG1 
                 proteoglycan 1, secretory granule 
                 NM_002727 
                 57 
               
               
                   
                 unnamed protein product; diaminopimelate decarboxylase 
                   
                   
               
               
                   
                 (AA 1-327);  Bacillus subtilis  lys gene for diaminopimelate 
                 X17013 
                 58 
               
               
                   
                 decarboxylase (EC 4.1.1.20). 
                   
                   
               
               
                 GPR43 
                 G protein-coupled receptor 43 
                 NM_005306 
                 60 
               
               
                 SPRR1A 
                 small proline-rich protein 1A 
                 NM_005987 
                 62 
               
               
                 SOD2 
                 superoxide dismutase 2, mitochondrial 
                 NM_000636 
                 67 
               
               
                 OLR1 
                 oxidised low density lipoprotein (lectin-like) receptor 1 
                 NM_002543 
                 66 
               
               
                   
                 synonyms: HIS, HSI, ARL1, ARL-1, ALDRLn, AKR1B11, 
                   
                   
               
               
                   
                 AKR1B12, MGC14103; aldose reductase-like 1; aldo-keto 
                   
                   
               
               
                 AKR1B10 
                 reductase family 1, member B11 (aldose reductase-like); 
                 NM_004812 
                 74 
               
               
                   
                 aldose reductase-like peptide; aldose reductase-related 
                   
                   
               
               
                   
                 protein; small intestine reductase; go —   
                   
                   
               
               
                   
                 synonyms: HIS, HSI, ARL1, ARL-1, ALDRLn, AKR1B11, 
                   
                   
               
               
                   
                 AKR1B12, MGC14103; aldose reductase-like 1; aldo-keto 
                   
                   
               
               
                 AKR1B10 
                 reductase family 1, member B11 (aldose reductase-like); 
                 NM_020299 
                 75 
               
               
                   
                 aldose reductase-like peptide; aldose reductase-related 
                   
                   
               
               
                   
                 protein; small intestine reductase; go —   
                   
                   
               
               
                 EMP1 
                 epithelial membrane protein 1 
                 NM_001423 
                 76 
               
               
                 HM74 
                 putative chemokine receptor 
                 NM_006018 
                 78 
               
               
                 HIST1H1C 
                 histone 1, H1c 
                 NM_005319 
                 83 
               
               
                 CCR1 
                 chemokine (C—C motif) receptor 1 
                 NM_001295 
                 94 
               
               
                 KRT13 
                 keratin 13 
                 NM_153490 
                 97 
               
               
                 PLAU 
                 plasminogen activator, urokinase 
                 NM_002658 
                 98 
               
               
                 IL1A 
                 interleukin 1, alpha 
                 NM_000575 
                 107 
               
               
                 SPRR2B 
                 small proline-rich protein 2B 
                 NM_001017418 
                 109 
               
               
                 SPRR1B 
                 small proline-rich protein 1B (cornifin) 
                 NM_003125 
                 117 
               
               
                 S100A2 
                 S100 calcium binding protein A2 
                 NM_005978 
                 134 
               
               
                 LILRB2 
                 leukocyte immunoglobulin-like receptor, subfamily B (with 
                 NM_005874 
                 145 
               
               
                   
                 TM and ITIM domains), member 2 
                   
                   
               
               
                 C4.4A 
                 GPI-anchored metastasis-associated protein homolog 
                 NM_014400 
                 146 
               
               
                 CPA4 
                 carboxypeptidase A4 
                 NM_016352 
                 153 
               
               
                 LILRB1 
                 leukocyte immunoglobulin-like receptor, subfamily B (with 
                 NM_006669 
                 160 
               
               
                   
                 TM and ITIM domains), member 1 
                   
                   
               
               
                 FCGR2A 
                 Fc fragment of IqG, low affinity IIa, receptor for (CD32) 
                 NM_021642 
                 163 
               
               
                   
               
               
                 * corrected accession number in Genbank 
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 17 
               
             
             
               
                   
               
               
                 Pooled samples 
               
               
                 Exacerbated Asthma two-fold decrease 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 CLGN 
                 calmegin 
                 NM_004362 
                 13 
               
               
                 FLJ13615 
                 hypothetical protein FLJ13615 
                 NM_025114 
                 25 
               
               
                 FLJ23505 
                   Homo sapiens  cDNA: FLJ23505 fis, clone LNG03017 
                 NM_024716 
                 68 
               
               
                 KIF3A 
                 kinesin family member 3A 
                 NM_007054 
                 80 
               
               
                 IGFBP7 
                 insulin-like growth factor binding protein 7 
                 NM_001553 
                 81 
               
               
                 TSAP6 
                 tumor suppressor pHyde;  Homo sapiens  dudulin 2 (TSAP6), 
                 NM_182915 
                 82 
               
               
                   
                 mRNA. 
                   
                   
               
               
                 PLTP 
                 phospholipid transfer protein 
                 NM_006227 
                 91 
               
               
                 SIAH1 
                 seven in absentia homolog 1 ( Drosophila ) 
                 NM_003031 
                 100 
               
               
                 TCF2 
                 transcription factor 2, hepatic; LF-B3; variant hepatic 
                 NM_006481 
                 113 
               
               
                   
                 nuclear factor 
                   
                   
               
               
                 LOC123872 
                 similar to RIKEN cDNA 4930457P18 
                 NM_178452 
                 121 
               
               
                 DCDC2 
                 doublecortin domain containing 2 
                 NM_016356 
                 127 
               
               
                 HPX 
                 hemopexin 
                 NM_000613 
                 141 
               
               
                 DNAI2 
                 dynein, axonemal, intermediate polypeptide 2 
                 NM_023036 
                 143 
               
               
                 C18orf1 
                 alternatively spliced; beta-1 form; possible membrane- 
                 NM_181481 
                 164 
               
               
                   
                 spanning protein; clone 22;  Homo sapiens  chromosome 18 
                   
                   
               
               
                   
                 open reading frame 1 (C18orf1), mRNA. 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 18 
               
             
             
               
                   
               
               
                 Pooled samples 
               
               
                 Exacerbated Asthma three-fold decrease 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 SF1 
                 splicing factor 1 
                 NM_004630 
                 11 
               
               
                 KCTD7 
                 potassium channel tetramerisation domain containing 7 
                 NM_153033 
                 12 
               
               
                 MYLK 
                 myosin, light polypeptide kinase 
                 NM_053025 
                 111 
               
               
                   
                   Homo sapiens  cDNA FLJ12411 fis, clone MAMMA1002964. 
                 AK022473 
                 118 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 19 
               
             
             
               
                   
               
               
                 Pooled samples 
               
               
                 Stable Asthma two-fold increase 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 FOS 
                 v-fos FBJ murine osteosarcoma viral oncogene homolog 
                 NM_005252 
                 28 
               
               
                 AQP9 
                 aquaporin 9 
                 NM_020980 
                 33 
               
               
                 IL1B 
                 interleukin 1, beta 
                 NM_000576 
                 41 
               
               
                 S100A9 
                 S100 calcium binding protein A9 (calgranulin B) 
                 NM_002965 
                 44 
               
               
                 PLEK 
                 pleckstrin 
                 NM_002664 
                 45 
               
               
                 OLR1 
                 oxidised low density lipoprotein (lectin-like) receptor 1 
                 NM_002543 
                 69 
               
               
                 JUNB 
                 jun B proto-oncogene 
                 NM_002229 
                 139 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 20 
               
             
             
               
                   
               
               
                 Pooled samples 
               
               
                 Stable Asthma three-fold increase 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 KRT6A 
                 keratin 6A 
                 NM_005554 
                 17 
               
               
                 CALB1 
                 calbindin 1, 28 kDa 
                 NM_004929 
                 18 
               
               
                 PDE4B 
                 phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 
                 NM_002600 
                 27 
               
               
                   
                 dunce homolog,  Drosophila ) 
                   
                   
               
               
                 HAL 
                 histidine ammonia-lyase 
                 NM_002108 
                 30 
               
               
                 ZNF407 
                 zinc finger protein 407 
                 NM_017757 
                 31 
               
               
                 CYP1A1 
                 cytochrome P450, family 1, subfamily A, polypeptide 1 
                 NM_000499 
                 35 
               
               
                 LILRB1 
                 leukocyte immunoglobulin-like receptor, subfamily B (with TM 
                 NM_006669 
                 42 
               
               
                   
                 and ITIM domains), member 1 
                   
                   
               
               
                 DTNA 
                 dystrobrevin, alpha 
                 NM_001390 
                 47 
               
               
                   
                 unnamed protein product; diaminopimelate decarboxylase (AA 
                   
                   
               
               
                   
                 1-327);  Bacillus subtilis  lys gene for diaminopimelate 
                 X17013 
                 58 
               
               
                   
                 decarboxylase (EC 4.1.1.20). 
                   
                   
               
               
                 IL1A 
                 interleukin 1, alpha 
                 NM_000575 
                 107 
               
               
                 LILRB2 
                 leukocyte immunoglobulin-like receptor, subfamily B (with TM 
                 NM_005874 
                 145 
               
               
                   
                 and ITIM domains), member 2 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 21 
               
             
             
               
                   
               
               
                 Pooled samples 
               
               
                 Stable Asthma two-fold decrease 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 SF1 
                 splicing factor 1 
                 NM_004630 
                 11 
               
               
                 FCGR2B 
                 Fc fragment of IgG, low affinity IIb, receptor for (CD32) 
                 NM_004001 
                 19 
               
               
                 BCL6 
                 B-cell CLL/lymphoma 6 (zinc finger protein 51) 
                 NM_138931 
                 21 
               
               
                 IPW 
                   Homo sapiens  mRNA; cDNA DKFZp686M12165 (from clone 
                 BX648788 
                 89 
               
               
                   
                 DKFZp686M12165) 
               
               
                 TCF2 
                 transcription factor 2, hepatic; LF-B3; variant hepatic nuclear 
                 NM_006481 
                 113 
               
               
                   
                 factor 
               
               
                 SPAG8 
                 sperm associated antigen 8 
                 NM_012436 
                 130 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 22 
               
             
             
               
                   
               
               
                 Pooled samples 
               
               
                 Stable Asthma three-fold decrease 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 SOSTDC1 
                 sclerostin domain containing 1 
                 NM_015464 
                 15 
               
               
                 RPEL1 
                 RPEL repeat containing 1 
                 AB051520 
                 51 
               
               
                 PLAU 
                 plasminogen activator, urokinase 
                 NM_002658 
                 98 
               
               
                 C12orf6 
                 chromosome 12 open reading frame 6 
                 NM_020367 
                 102 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 23 
               
             
             
               
                   
               
               
                 Genes F ST  &gt; 0.25 between Caucasians and Han Chinese from 161 gene dataset 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 PDE4B 
                 phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 
                 NM_002600 
                 27 
               
               
                   
                 dunce homolog,  Drosophila ) 
               
               
                 ADCY2 
                 adenylate cyclase 2 (brain) 
                 NM_020546 
                 46 
               
               
                 KIF3A 
                 kinesin family member 3A 
                 NM_007054 
                 80 
               
               
                 HIST1H1C 
                 histone 1, H1c 
                 NM_005319 
                 83 
               
               
                 PLAU 
                 plasminogen activator, urokinase 
                 NM_002658 
                 98 
               
               
                 FLJ40427 
                 hypothetical protein FLJ40427 
                 NM_178504 
                 108 
               
               
                 SPRR2B 
                 small proline-rich protein 2B 
                 NM_001017418 
                 109 
               
               
                 MYLK 
                 myosin, light polypeptide kinase 
                 NM_053025 
                 111 
               
               
                 DNAH5 
                 dynein, axonemal, heavy polypeptide 5 
                 NM_001369 
                 115 
               
               
                 SLC26A7 
                 solute carrier family 26, member 7 
                 NM_052832 
                 119 
               
               
                 CHST5 
                 carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 5 
                 NM_024533 
                 122 
               
               
                 ZNF483 
                 zinc finger protein 483 
                 NM_007169 
                 150 
               
               
                 ZNF483 
                 zinc finger protein 483 
                 NM_133464 
                 151 
               
               
                 SCARF2 
                 scavenger receptor class F, member 2 
                 NM_153334 
                 159 
               
               
                 C18orf1 
                 alternatively spliced; beta-1 form; possible membrane- 
                 NM_181481 
                 164 
               
               
                   
                 spanning protein; clone 22;  Homo sapiens  chromosome 18 
               
               
                   
                 open reading frame 1 (C18Sorf1), mRNA. 
               
               
                 MYEF2 
                 myelin expression factor 2 
                 NM_016132 
                 165 
               
               
                 KCNC3 
                 potassium voltage-gated channel, Shaw-related subfamily, 
                 NM_004977 
                 166 
               
               
                   
                 member 3 
               
               
                   
               
               
                 * corrected accession number in Genbank 
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 24 
               
             
             
               
                   
               
               
                 Genes 0.15 &lt; F ST  &lt; 0.25 between Caucasians and Han Chinese from 161 gene dataset 
               
             
          
           
               
                   
                   
                   
                 Seq. ID 
               
               
                 Common 
                 Description 
                 Genbank 
                 Number 
               
               
                   
               
             
          
           
               
                 CALB1 
                 calbindin 1, 28 kDa 
                 NM_004929 
                 18 
               
               
                 HAL 
                 histidine ammonia-lyase 
                 NM_002108 
                 30 
               
               
                 ZNF407 
                 zinc finger protein 407 
                 NM_017757 
                 31 
               
               
                 SLC2A14 
                 solute carrier family 2 (facilitated glucose transporter), 
                 NM_153449 
                 32 
               
               
                   
                 member 14 
               
               
                 BCL2A1 
                 BCL2-related protein A1 
                 NM_004049 
                 34 
               
               
                 ZCCHC2 
                 zinc finger, CCHC domain containing 2 
                 NM_017742 
                 38 
               
               
                 ALDH1A3 
                 aldehyde dehydrogenase 1 family, member A3 
                 NM_000693 
                 39 
               
               
                 PLEK 
                 pleckstrin 
                 NM_002664 
                 45 
               
               
                 DTNA 
                 dystrobrevin, alpha 
                 NM_001390 
                 47 
               
               
                 ARNTL2 
                 aryl hydrocarbon receptor nuclear translocator-like 2 
                 NM_020183 
                 48 
               
               
                 EMP1 
                 epithelial membrane protein 1 
                 NM_001423 
                 55 
               
               
                 PRG1 
                 proteoglycan 1, secretory granule 
                 NM_002727 
                 57 
               
               
                 DNAH7 
                 dynein, axonemal, heavy polypeptide 7 
                 NM_018897 
                 63 
               
               
                 SCEL 
                 sciellin 
                 NM_144777 
                 77 
               
               
                 DNCI1 
                 dynein, cytoplasmic, intermediate polypeptide 1 
                 NM_004411 
                 85 
               
               
                 MGC26733 
                 hypothetical protein MGC26733 
                 NM_144992 
                 104 
               
               
                 TCF2 
                 transcription factor 2, hepatic; LF-B3; variant hepatic 
                 NM_006481 
                 113 
               
               
                   
                 nuclear factor 
               
               
                 CLECSF12 
                 C-type (calcium dependent, carbohydrate-recognition 
                 NM_197953 
                 114 
               
               
                   
                 domain) lectin, superfamily member 12 
               
               
                 DNAH9 
                 dynein, axonemal, heavy polypeptide 9 
                 NM_001372 
                 116 
               
               
                 EAT2 
                 SH2 domain-containing molecule EAT2 
                 NM_053282 
                 120 
               
               
                 PRV1 
                 polycythemia rubra vera 1 
                 NM_020406 
                 129 
               
               
                 DNAI2 
                 dynein, axonemal, intermediate polypeptide 2 
                 NM_023036 
                 143 
               
               
                   
                 UI-H-EZ1-bbk-j-02-0-UI.s1 NCI_CGAP_Ch2  Homo sapiens   
               
               
                 LOC165186 
                 cDNA clone UI-H-EZ1-bbk-j-02-0-UI 3′, mRNA sequence.; 
                 NM_199280 
                 144 
               
               
                   
                 ESTs, Weakly similar to T00057 hypothetical protein 
               
               
                   
                 KIAA0423 - human (fragment) [ H. sapiens ] 
               
               
                 SLC30A7 
                 solute carrier family 30 (zinc transporter), member 7 
                 NM_133496 
                 152 
               
               
                 LILRB1 
                 leukocyte immunoglobulin-like receptor, subfamily B (with 
                 NM_006669 
                 160 
               
               
                   
                 TM and ITIM domains), member 1 
               
               
                 DNAH3 
                 dynein, axonemal, heavy polypeptide 3 
                 NM_017539 
                 167 
               
               
                   
               
             
          
         
       
     
     Other variations or embodiments of the invention will also be apparent to one of ordinary skill in the art from the above figures, tables, and description. Thus, the forgoing embodiments are not to be construed as limiting the scope of this invention.