Patent Publication Number: US-2009220973-A1

Title: Obesity and body fat distribution

Description:
FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     This invention was made with Government support under Grant Nos. ROI DK33201, DK60837, and K08DK064906, awarded by the National Institutes of Health. The U.S. Government has certain rights in the invention. 
    
    
     TECHNICAL FIELD 
     This invention relates to methods of predicting obesity and body fat distribution, and methods of identifying compounds for the treatment of obesity or the manipulation of body fat distribution. 
     BACKGROUND 
     Obesity is an epidemic health problem worldwide that impacts on the risk and prognosis of many diseases, including diabetes, cardiovascular disease, hyperlipidemia, and cancer (Lean, (2000) Proc Nutr Soc 59, 331-6). However, not all obese patients have the same risk of developing these disorders. Individuals with peripheral obesity, i.e., fit distributed subcutaneously in the gluteofemoral region, are at little or no risk of the common medical complications of obesity, whereas individuals with central obesity, i.e., fat accumulated in visceral depots, are prone to these complications (Mauriege et al., (1993) Eur J Clin Invest 23, 729-40; Gillum, (1987) J Chronic Dis 40, 421-8; Kissebah and Krakower, (1994) Physiol Rev 74, 761-811; and Abate and Garg, (1995) Prog Lipid Res 34, 53-70). 
     While differentiation of adipocytes has been extensively characterized (Gregoire, (2001) Exp Biol Med (Maywood) 226, 997-1002; Koutnikova and Auwerx, (2001) Ann Med 33, 556-61; and Tong and Hotamisligil, (2001) Rev Endocr Metab Disord 2, 349-55) and there have been considerable recent insights into the control of appetite and energy expenditure as contributing factors to obesity (Wynne et al., (2005) J Endocrinol 184, 291-318; Ricquier, (2005) Proc Nutr Soc 64, 47-52), little is known about the genetic basis for determination of adipocyte number, differences in body fat distribution or their association with metabolic disorders. Twin and population studies have revealed that both body mass index (BMI) and waist-hip ratio (WHR) are heritable traits, with genetics accounting for 25-70% of the observed variability (Nelson et al., (2000) Twin Res 3, 43-50; and Baker et al., (2005) Diabetes 54, 2492-6). In addition, it is known that some obese individuals, especially those with early onset obesity, have increased numbers of adipocytes, but how these are distributed and why this occurs is unknown (Hirsch and Batchelor, (1976) Clin Endocrinol Metab 5, 299-311). Anecdotally, it is also clear that individual humans observe differences in their own body fat distribution as they gain or lose weight. 
     The uneven distribution of adipose tissue is extreme in some ethic groups, such as Hottentot women, who have been noted for excessive accumulation of fat in the buttocks, a condition known as steatopygia (Ersek et al., (1994) Aesthetic Plast Surg 18, 279-82). Striking differences in adipose tissue distribution can also be observed in individuals with partial lipodystrophy (Garg and Misra, (2004) Endocrinol Metab Clin North Am 33, 305-31), both in its acquired and inherited forms. For example, familial partial lipodystrophy of the Dunnigan type due to mutations in the Lamin A/C gene is characterized by a marked loss of subcutaneous adipose tissue in the extremities and trunk, without loss of visceral, neck or facial adipose tissue (Garg et al., (1999) J Clin Endocrinol Metab 84, 1704; Shackleton et al., (2000) Nat Genet 24, 153-6). Some lipodystrophies even appear to have a segmental or dermatomal distribution (Shelley and Izumi, (1970) Arch Dermatol 102, 326-9). 
     SUMMARY 
     At least in pare the present invention is based on the discovery of major differences in expression of multiple genes involved in embryonic development and pattern specification between adipocytes taken from intra-abdominal and subcutaneous depots in rodents and humans. Similar differences were also present in the stromovascular fraction containing preadipocytes and that these differences persist in culture. Some of these developmental genes exhibit changes in expression that are closely correlated with level of obesity and the pattern of fat distribution. 
     In one aspect, the invention provides methods for diagnosing present obesity, e.g., high body mass index (BMI), or of predicting future obesity or undesirable adipose tissue distribution, e.g., high waist-hip ratio (WHR), in a subject, e.g., a human. The methods include providing a sample comprising a tissue or cell, e.g., an adipose tissue or cell, from the subject; and evaluating the level of mRNA in the cell for one, two, three, four or more of the genes listed in Table 1, e.g., one or more of Tbx15, Shox2, En1, Sfrp2, HoxC9, Nr2f1, Gpc4, Thbd, HoxA5 or HfoxC8, or a level of a protein encoded thereby. The level of expression, e.g., as compared to a predetermined reference level (e.g., as described herein), indicates whether the subject has, or is at risk of developing, obesity or undesirable adipose tissue distribution. 
     In some embodiments, the methods include determining a level of expression of at least one mRNA for a gene selected from the group consisting of Hox57, Gpc4 and Tbx15 in human adipose tissue, or a level of a protein encoded thereby, and comparing the levels to a reference, e.g., a reference that represents a subject with a selected BMI, e.g., a normal or near normal BMI. In some embodiments, the methods include measuring levels for one or both of Tbx15 in visceral fat and Gpc4 in subcutaneous fat. 
     In some embodiments, the relationship of the levels for the mRNA or protein in the human subject and the reference indicates whether the subject has or will develop an unhealthy BMI. The level of the mRNA or protein is used to select or exclude a subject for participation in a clinical trial. 
     In some embodiments, the subject is given a treatment or preventive measure for obesity, and the level of the mRNA or protein is correlated with the subject&#39;s response to the treatment or preventive measure for obesity. For example, the level of the protein or mRNA can be determined before, during and/or after the treatment, and a change in the level of the protein or mRNA indicates whether the subject is responding or has responded to the treatment. 
     In another aspect, the invention provides methods for determining a ratio of intra-abdominal (visceral) accumulation of fat versus subcutaneous (peripheral) fat in a subject. The methods include providing a first sample from the subject comprising visceral adipose cells or tissue; providing a second sample from the subject comprising peripheral adipose cells or tissue; quantifying a level of mRNA in the first and second samples for one, two, three, four or more of the genes listed in Table 1, e.g., one or more of Tbx15, Shox2, En1, Sfrp2, HoxC9, Nr2f1, Gpc4, Thbd, HoxA5 or HoxC8, or a level of a protein encoded thereby; and determining a ratio of the level of mRNA or protein in the first sample to the level of mRNA in the second sample. The ratio of the level of mRNA or protein in the first sample to the level of mRNA in the second sample indicates the ratio of visceral accumulation of fat versus peripheral fat in the subject. These methods can also be used to predict future undesirable distribution of weight. 
     In a her aspect, the invention provides methods for identifying a candidate compound, e.g., for the treatment of obesity. The methods include providing a sample comprising an adipose cell or tissue expressing one, two, three, four or more of the genes listed in Table 1, e.g., one or more of Tbx15, Shox2, En1, Sfrp2, HoxC9, Nr2f1, Gpc4, Thbd, HoxA5 or HoxC8; contacting the cell or tissue with a test compound, e.g., a small organic or inorganic molecule, an inhibitory or stimulatory nucleic acid, or a polypeptide; and evaluating the expressing of the one, two, three, four or more of the genes listed in Table 1, e.g., one or more of Tbx15, Shox2, En1, Sfrp2, HoxC9, Nr2f1, Gpc4, Thbd, HoxA5 or HoxC8, in the cell. A test compound that appropriately-modulates the expression of the gene or genes is a candidate compound for the treatment of obesity. 
     Further, the invention provides additional methods for identifying a candidate compound, e.g., for the treatment of obesity. The methods include providing a sample comprising one, two, three, four or more proteins expressed by a gene listed in Table 1, e.g., one or more of Tbx15, Shox2, En1, Sfrp2, HoxC9, Nr2f1, Gpc4, Thbd, HoxA5 or HoxC8, or a cell or tissue expressing the proteins; contacting the sample with a test compound, e.g., a small organic or inorganic molecule, an inhibitory or stimulatory nucleic acid, or a polypeptide; and evaluating the level or activity of the protein in the sample. A test compound that appropriately modulates, e.g., increases or decreases, the level or activity of the protein is a candidate compound for the treatment of obesity. 
     Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Exemplary methods and materials are described herein for use in the present invention; other, suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. 
     Other features and advantages of the invention will be apparent from the following detailed description and figures, and from the claims. 
    
    
     
       DESCRIPTION OF DRAWINGS 
         FIG. 1A  is a schematic illustration of the experimental design used in some of the examples set forth herein. Flank subcutaneous and intra-abdominal (epididymal) white adipose tissues were taken from 6-7 week old pooled C5Tb1/6 males. Stromovascular fraction and adipocytes were isolated after collagenase digestion of adipose tissues. Equal quantities of RNA were isolated from isolated adipocytes and stromovascular fraction of each fat depot. A hybridization mixture containing 15 μg of biotinylated cRNA, adjusted for possible carryover of residual total RNA, was prepared and hybridized to mouse Affymetrix U74Av2 chips. 
         FIG. 1B  is a diagram illustrating some of the results described herein. Among the 12,488 probesets present on the U74Av2 chip, 8,017 probesets representing 6174 are annotated for Gene Ontology Biological Process. Significant genes with differential expression in both depots were identified by selecting genes that passed two independent filters of significance (p-value Student&#39;s t-test &lt;0.05 and pFDR &lt;0.05) (see Methods). The first filter p-value Student&#39;s t-test &lt;0.05) selected 1,276 genes differentially expressed in the stromovascular fraction, 537 genes differentially expressed in isolated adipocytes and 233 genes differentially expressed in both cell fractions. Of these 233 genes, 197 genes passed the second filter of significance (PFDR &lt;0.05) and were assessed against an a priori set of 198 annotated genes involved in embryonic development and pattern specification (see Methods). Twelve genes from this set were found among the differentially expressed genes. 
         FIGS. 2A-C  are bar graphs illustrating the results of a comparison of Tbx15, Shox2, En1, Sfrp2 and HoxC9 gene expression between intra-abdominal (Epi; opened bars) and subcutaneous (SC; closed bars) adipose tissue of C57316 mice performed using real time PCR. These genes had a higher level of expression in subcutaneous in whole adipose tissue (2A) (Epi versus Sc; * p-value &lt;0.05), isolated adipocytes and stromovascular fraction (2B) (Epi versus Sc; * p-value &lt;0.05). These differences of expression were maintained when stromovascular fraction taken from intra-abdominal (epididymal) or subcutaneous adipose were placed in culture in a defined serum free medium and subjected to in vitro differentiation (2C) suggesting these differences are independent of extrinsic factors (Epi versus Sc; * p-value &lt;0.05) 
         FIGS. 3A-3C  are bar graphs illustrating the results of a comparison of Nr2f1, Gpc4, Thbd, HoxA5 and HoxC8 gene expression between intra-abdominal (Epi; opened bars) and subcutaneous (SC; closed bars) adipose tissue of C57B16 mice performed using real time PCR. These genes had a higher level of expression in intra-abdominal (epidydimal) whole adipose tissue ( 3 A) (Epi versus Sc; * p-value &lt;0.05), isolated adipocytes and stromovascular fraction ( 3 B) (Bpi versus Sc; * p-value &lt;0.05). These differences of expression were maintained when stromovascular fraction taken from intra-abdominal (epididymal) or subcutaneous adipose were placed in culture in a defined serum free medium and subjected to in vitro differentiation ( 3 C) suggesting these differences are independent of extrinsic factors (Epi versus Sc; * p-value &lt;0.05) 
         FIGS. 4A-4J  are bar graphs illustrating differential expression of subcutaneous dominant genes and intra-abdominal dominant genes in subcutaneous and intra-abdominal adipose tissue of lean humans. Visceral (Vis, opened bars) and subcutaneous (SC, closed bars) adipose tissue biopsies were performed on 53 lean subjects (BMI&lt;25; 22 males and 31 females). Shox2 ( 4 A), En1 ( 4 B), HoxC9 ( 4 C), Sfrp2 ( 4 D), Tbx15 ( 4 E), Nr2f1 ( 4 F), Thbd ( 4 G), HoxA5 ( 4 H), HoxC8 ( 4 I), and Gpc4 ( 4 J) expression levels were compared in both depots using real time PCR (Vis versus SC, * p&lt;0.05). 
         FIGS. 5A and 5B  are each sets of six scatter/line graphs illustrating expression of HoxA5, Gpc4 and Tbx15 in subcutaneous and visceral adipose tissue in human are correlated with adiposity and fat distribution. One hundred ninety eight subjects (99 males and 99 females) ranging from lean to obese with variable BMI ( 5 A) and fat distribution (WHR) ( 5 B) were subjected to visceral (Vis, opened bars) and subcutaneous (SC, closed bars) adipose tissue biopsies. Gene expression of HoxA5 (top panels), Gpc4 (middle panels) and Tbx15 (bottom panels) was assessed in both fat depots by real time PCR as described in Materials and Methods. Correlation significances were determined using Stat View software, either as linear correlations or in the case of non-linear correlations by exponential or lowess curve fitting. 
         FIG. 6  is a schematic diagram illustrating a hypothetical scheme of adipocyte development, not meant to be limiting. 
     
    
    
     DETAILED DESCRIPTION 
     Obesity is a multifactorial disorder influenced by a mixture of genetic and environmental factors, including control of appetite and energy expenditure, availability and nutritional content of food, and development of adipocyte cell mass. Furthermore, obesity occurs with different degrees of fat accumulation in different depots, and these are associated with different metabolic consequences with intra-abdominal (visceral) accumulation of fat producing a much greater risk of diabetes, dyslipidemia and accelerated atherosclerosis than subcutaneous (peripheral) fat. The accumulation of visceral fat, e.g., as opposed to peripheral fat, is referred to herein as “undesirable body fat distribution.” 
     Although obesity and body fat distribution are clearly hereditable traits, the role of developmental genes in obesity and fat distribution has received surprisingly little attention. Stromovascular fractions taken from different adipose depots (Djian et al., (1983) J Clin Invest 72, 1200-8, Adams et al., (1997) J Clin Invest 100, 3149-53; Kirkland et al., (1990) Am J Physiol 258, C206-10; Hauner and Entenmann, (1991) Int J Obes 15, 121-6; Tchkonia et al., (2002) Am J Physiol Regul Integr Comp Physiol 282, R1286-96; and Tchkonia et al., (2005) Am J Physiol Endocrinol Metab 288, E267-77) and from obese versus lean individuals show differing propensity to differentiate when place in tissue culture in vitro (van Harmelen et al., (2003) Int J Obes Relat Metab Disord 27, 889-95). In addition, the rate of lipolysis in adipose tissue taken from subcutaneous sites is lower than of adipose tissue from visceral or omental sites (Amer, (1995) Ann Med 27, 435-8). Furthermore, the lipolytic effect of catecholamines is weaker and the antilipolytic effect of insulin is more pronounced in subcutaneous as compared to visceral adipose tissue (Mauriege et al., (1987) Fur J Clin Invest 17, 156-65; and Bolinder et al., (1983) Diabetes 32, 117-23). 
     Characterization of differences in gene expression between human subcutaneous and visceral adipose tissue also suggest genetic/developmental heterogeneity. Acylation stimulating protein and angiotensinogen mRNA levels are higher in visceral adipose, whereas the levels of leptin, PPARγ, GLUT4, glycogen synthase and cholesterol ester transfer protein (CETP) are higher in the subcutaneous depot (Lefebvre et al., (1998) Diabetes 47, 98-103; and Dusserre et al., (2000) Biochim Biophys Acta 1500, 88-96). In a survey of genes differentially expressed in subcutaneous and visceral adipose tissue in men, Vohl et al. ((2004) Obes Res 12, 1217-22) also noted differences in genes involved in lipolysis, cytokine secretion, Wnt signaling, C/EPBα and some HOX genes. Differences in large and small adipocytes taken from normal and fat insulin receptor knockout (FIRKO) mice with regard to function, gene and protein expression have also been observed (Bluher et al., (2002) Dev Cell 3, 25-38; Bluher et al., (2004) J Biol Chem 279, 31891-901; and Bluher et al., (2004) J Biol Chem 279, 31902-9). The present study, therefore, explored the hypothesis that developmental genes might play an important role in obesity and body fat distribution in both rodents and humans. 
     Using microarray and qPCR analysis, 197 genes were found to be differentially expressed in both adipocytes and SVF-containing preadipocytes from subcutaneous and intra-abdominal depots of the mouse; of these, at least 12 are genes previously thought to play a role in early development and pattern specification. Of these, Tbx15, Shox2, En1, Sfrp2 and HoxC9 were more highly expressed in cells of subcutaneous adipose tissue, whereas Nr2f1, Gpc4, Thbd, HoxA5 and HoxC8 were more expressed in intra-abdominal adipose tissue. These differences in gene expression are intrinsic and persist during in vitro culture and differentiation indicating that they are cell autonomous and independent of tissue microenvironment. Since the expression of these developmental genes emerges during embryogenesis, before any white adipose tissue can be detected, and is maintained during adult life, this suggests that different adipocyte precursors are responsible for a specific adipose depot development and may participate later in the functional differences observed between internal and subcutaneous adipose depots. 
     Methods of Diagnosis 
     Included herein are methods for diagnosing obesity, for quantifying distribution of body fat, and for predicting fixture obesity and undesirable body fat distribution. The methods include obtaining a sample from a subject, e.g., a sample comprising a brown or white adipocyte or preadipocyte, and evaluating the presence and/or level of one, two, three, four or more of the genes listed in Table 1, e.g., one or more of Tbx15, Shox2, En1, Sfrp2, HoxC9, Nr2f1, Gpc4, Thbd, HoxA5 or HoxC8 in the sample, and comparing the presence and/or level with one or more references, e.g., a control reference that represents a normal level of the gene or genes, e.g., a level in an unaffected subject, and/or a disease reference that represents a level of the proteins associated with obesity or undesirable distribution of body fat, e.g., a level in a subject having excessive amounts of visceral fat. Suitable reference values can include those shown in FIG.  4 /Example 4. 
     Differential Gene Expression in Mice and Humans 
     While all of the genes that were differentially expressed in rodents were also differentially expressed in humans, in some cases, the direction of difference was different in the two species. This may reflect the fact that fat was not taken from identical depots in the two species or may simply represent differences between development in these two species. Other differences in gene expression have also been observed between humans and rodents. Thus, leptin exhibits a higher expression in subcutaneous than omental adipose in humans (Lefebvre et al., (1998) Diabetes 47, 98-103; and Dusserre et al., (2000) Biochim Biophys Acta 1500, 88-96), whereas in mice, leptin expression is higher in intra-abdominal (epididymal) fat than subcutaneous fat (Trayhurn et al., (1995) FEBS Let 368, 488-90). Likewise, the differential expression of α 2 -adrenergic receptor expression observed in humans (higher in subcutaneous adipose than in omental) Mauriege et al., (1987) Eur J Clin Invest 17, 156-65) is not observed at all in mice, which do not express α 2 -adrenergic receptors in adipose tissue (Castan et al., (1994) Am J Physiol 266, R1141-7). Conversely, β 3 -adrenergic receptors are widely expressed in mouse adipose tissue, whereas little or no expression has been reported in human adipose (Lafontan (1994) Cell Signal 6, 363-92). In our case, the interdepot differences of expression for developmental genes Shox2, En1, Nr2f1, HoxA5. HoxC8 and Thbd were preserved from mice to humans independent of gender, whereas interdepot differential expression of HoxC9 in humans occurred only in females, and Tbx15, Sfrp2 and Gpc4 exhibited opposite directions of differential expression in mice and humans. In both species, what is clear is that multiple developmental genes, including those involved in antero-posterior or dorso-ventral patterning, exhibit dramatic differences in level of expression in adipose and preadipose from different regions of the body. 
     Correlation of Gene Expression with Body Mass Index (BMI) 
     One of the most striking features of the expression of HoxA5, Gpc4 and Tbx15 in human adipose is not only their differential expression between depots, but their strong correlation with BMI. This is particularly true for Tbx15 in visceral fat and Gpc4 in subcutaneous fat such that both genes show dramatic changes in expression as BMI goes from the normal range (20-25) to either overweight (25-30) or obese (&gt;30). 
     No other parameter related to obesity or fat mass, including serum leptin, adiponectin or insulin, shows such a distinct change at this transition point. Indeed, if the physiological separation between lean and overweight/obese had not been previously defined by epidemiological criteria, one could define the overweight population by the expression level of these genes, suggesting that expression of these genes could related to the pathogenesis of obesity. 
     Thus, the methods described herein include determining levels of HoxA5; Gpc4 and Tbx15 in human adipose tissue, and comparing the levels to a reference, e.g., a reference that represents a subject with a selected BMI, e.g., a normal or near normal BMI. In some embodiments, the methods include measuring Tbx15 in visceral fat and/or Gpc4 in subcutaneous fat. The relationship of the levels of the genes in the human subject and the reference can be used to diagnose present obesity or predict the future likelihood that the subject will develop an unhealthy BMI. The levels of these genes can also be used to select subjects, e.g., stratify subjects, for participation in a clinical trial, and to correlate their expression with response to a given treatment or preventive measure for obesity. 
     Correlation of Gene Expression with Waist-Hip Ratio (WHR) 
     Distribution of adipose tissue (WHR) also has a strong heritable component (Baker et al., (2005) Diabetes 54, 2492-6) and has been shown to better correlate with risk of diabetes and atherosclerosis than BMI (Ohlson et al., (1985) Diabetes 34, 1055-8). Increased WHR, i.e., visceral/central or “apple shaped” obesity, also referred to herein as undesirable body fat distribution, is associated with higher risks for metabolic and cardiovascular complications (Mauriege et al., (1993) Eur J Clin Invest 23, 72940; Gillum, (1987) J Chronic Dis 40; 421-8; Kissebah and Krakower, (1994) Physiol Rev 74, 761-811; Abate and Garg, (1995) Prog Lipid Res 34, 53-70). Ideally, women should have a waist-to-hip ratio of 0.8 or less, and men should have a waist-to-hip ratio of 0.95 or less. 
     As described herein, HoxA5, Gpc4 and Tbx15 expression also vary with fat distribution, and that expression of the latter two is an excellent marker for visceral fat accumulation. Thus, high levels of Tbx15 and Gpc4 expression in subcutaneous adipose tissue and low levels of expression in visceral adipose tissue appear to be linked with high WHR and by extension should be correlated with higher risks for metabolic and cardiovascular complications. 
     Therefore, the methods described herein include evaluating the expression levels of these genes in adipose cells taken from different sites in the body, e.g., subcutaneous versus visceral fat depots, and comparing the expression levels to a reference level, a reference level that represents a subject with normal or close to normal body fat depots in the corresponding sites in the body. The difference between the level of expression of the gene in the subject&#39;s cells versus the reference will indicate whether there is, or in the future will be, an excessive (or insufficient) amount of adipose tissue in the relevant part of the body. As one example, levels of a gene that is listed in Table 1 for which increased expression is associated with increased adipose tissue will be indicative of increased adipose deposits if the level in the subject are above those in the reference. The converse is true for those genes for which decreased expression is associated with increased adipose depots. Thus, the methods described herein include determining levels of HoxA5, Gpc4, and Tbx15 in human adipose tissue, and comparing the levels to a reference, e.g., a reference that represents a subject with a selected WHR, e.g., a normal or near normal WHR. The relationship of the levels of the genes in the human subject and the reference can be used to diagnose present obesity or predict the future likelihood that the subject will develop an unhealthy WHR. The levels of these genes can also be used to select subjects, e.g., stratify subjects, for participation in a clinical trial, and to correlate their expression with response to a given treatment or preventive measure for obesity. 
     The methods can also include using standard mathematical algorithms to determine the ratio of expression of a given gene in the different fat depots, e.g., a ratio of expression between subcutaneous and visceral tissues, and comparing that ratio to a reference ratio, e.g., reference ration that represents a subject with normal or close to normal body fit distribution. Again, depending on whether increased or decreased expression of the gene is associated with increased adipose tissue depots, the relationship between the ratio in the subject and the reference ratio will be indicative of the presence or future likelihood of developing undesirable body fat distribution. The levels of these genes can also be used to select subjects, e.g., stratify subjects, for participation in a clinical trial, and to correlate their expression with response to a given treatment or preventive measure for obesity or undesirable body fat distribution. 
     For example, the methods can include measuring HoxA5, Gpc4 and Tbx15 in visceral fat and in subcutaneous fat. High levels of Tbx15 and Gpc4 expression in subcutaneous adipose tissue and low levels of expression in visceral adipose tissue indicate the presence or future likelihood of high WHR, and therefore higher risk for metabolic and cardiovascular complications 
     In some embodiments, the presence and/or level of the one or more genes is comparable to the presence and/or level of the one or more genes in the disease reference, and the subject has one or more symptoms or risk factors associated with obesity or undesirable body fat distribution, then the subject has, or is at an increased risk for, obesity or undesirable body fat distribution. In some embodiments, the subject has no overt signs or symptoms of obesity or undesirable body fat distribution, but the presence and/or level of one or more of the proteins evaluated is comparable to the presence and/or level of the protein(s) in the disease reference, then the subject has an increased risk of developing obesity or undesirable body fat distribution. For example, in a subject who is adolescent or pre-adolescent, the presence of a pathological level of the one or more genes may indicate that the subject is at an increased risk of future obesity or undesirable body fat distribution. 
     In some embodiments, the sample includes an adipose cell. In some embodiments, once it has been determined that a person has obesity or undesirable body fat distribution, or has an increased risk of developing obesity or undesirable body fat distribution, then a treatment, e.g., as known in the art or as described herein, can be administered. 
     Assay Methods 
     The presence and/or level of a gene or protein can be evaluated using methods known in the art, e.g., using standard Northern or Western analysis. In some embodiments, high throughput methods, e.g., protein or gene chips as are known in the art (see, e.g., Ch-12, “Genomies,” in Griftis et al., Eds.  Modern genetic Analysis,  1999, W.H. Freeman and Company; Ekis and Chu, Trends in Biotechnology, 1999, 17:217-218; MacBeath and Schreiber, Science 2000, 289(5485):1760-1763; Simpson,  Proteins and Proteomics: A Laboratory Manual , Cold Spring Harbor Laboratory Press; 2002; Hardiman,  Microarrays Methods and Applications: Nuts  &amp;  Bolts , DNA Press, 2003), can be used to detect the presence and/or level of the one or more genes. 
     In addition, methods for detecting or evaluating the activity of a selected protein are known in the art, and will vary depending on the protein selected. 
     Methods of Screening 
     The invention includes methods for screening of test compounds, to identify compounds that modulate the expression of one, two, three, four or more of the genes listed in Table 1, e.g., one or more of Tbx15, Shox2, En1, Sfrp2, HoxC9, Nr2f1, Gpc4, Thbd, HoxA5 or HoxC8, in a cell, e.g., an adipose cell, e.g., a brown or white adipocyte or preadipocyte. Assay methods useful in the methods of screening are described herein and known in the art. 
     In some embodiments, the test compounds are initially members of a library, e.g., an inorganic or organic chemical library, peptide library, oligonucleotide library, or mixed-molecule library. In some embodiments, the methods include screening small molecules, e.g., natural products or members of a combinatorial chemistry library. 
     A given library can comprise a set of structurally related or unrelated test compounds. Preferably, a set of diverse molecules should be used to cover a variety of frictions such as charge, aromaticity, hydrogen bonding, flexibility, size, length of side chain, hydrophobicity, and rigidity. Combinatorial techniques suitable for creating libraries are known in the a, e.g., methods for synthesizing libraries of small molecules, e.g., as exemplified by Obrecht and Villalgordo,  Solid - Supported Combinatorial and Parallel Synthesis of Small - Molecular - Weight Compound Libraries , Pergamon-Elsevier Science Limited (1998). Such methods include the “split and pool” or “parallel” synthesis techniques, solid-phase and solution-phase techniques, and encoding techniques (see, for example, Czarnik, Curr. Opin. Chem. Bio. 1:60-6 (1997)). In addition, a number of libraries, including small molecule libraries, are commercially available. 
     In some embodiments, the test compounds are peptide or peptidomimetic molecules, e.g., peptide analogs including peptides comprising non-naturally occurring amino acids or having non-peptide linkages; peptidomimetics (e.g., peptoid oligomers, e.g., peptoid amide or ester analogues, β-peptides, D-peptides, L-peptides, oligourea or oligocarbamate); small peptides (e.g., pentapeptides, hexapeptides, heptapeptides, octapeptides, nonapeptides, decapeptides, or larger, e.g., 20-mers or more); cyclic peptides; other non-natural or unnatural peptide-like structures, and inorganic molecules (e.g., heterocyclic ring molecules). In some embodiments, the test compounds are nucleic acids, e.g., DNA or RNA oligonucleotides. 
     In some embodiments, test compounds and libraries thereof can be obtained by systematically altering the structure of a first test compound. Taking a small molecule as an example, e.g., a first small molecule is selected that has been identified as capable of modulating the expression of one, two, three, four or more of the genes listed in Table 1, e.g., one or more of Tbx15, Shox2, En1, Sfrp2, HoxC9, Nr2f1, Gpc4, Thbd, HoxA5 or HoxC8. For example, in one embodiment, a general library of small molecules is screened, e.g., using the methods described herein, to select a fist test small molecule. Using methods known in the art, the structure of that small molecule is identified if necessary and correlated to a resulting biological activity, e.g., by a structure-activity relationship study. As one of skill in the art will appreciate, there are a variety of standard methods for creating such a structure-activity relationship. Thus, in some instances, the work may be largely empirical, and in others, the three-dimensional structure of an endogenous polypeptide or portion thereof can be used as a starting point for the rational design of a small molecule compound or compounds. 
     In some embodiments, test compounds identified as “hits” (e.g., test compounds that demonstrate the ability to modulate one, two, three, four or more of the genes listed in Table 1, e.g., one or more of Tbx15, Shox2, En1, Sfrp2, HoxC9, Nr2f1, Gpc4, Thbd, HoxA5 or HoxC8) in a first screen are selected and optimized by being systematically altered, e.g., using rational design, to optimize binding affinity, avidity, specificity, or other parameter. Such potentially optimized structures can also be screened using the methods described herein. Thus, in one embodiment the invention includes screening a first library of test compounds using a method described herein, identifying one or more hits in that library, subjecting those hits to systematic structural alteration to create one or more second generation compounds structurally related to the hit, and screening the second generation compound. Additional rounds of optimization can be used to identify a test compound with a desirable therapeutic profile. 
     Test compounds identified as hits can be considered candidate therapeutic compounds, useful in treating disorders described herein. Thus, the invention also includes compounds identified as “hits” by a method described herein, and methods for their administration and use in the treatment, prevention, or delay of development or progression of a disease described herein. 
     EXAMPLES 
     The invention is further described in the following examples, which do not limit the scope of the invention described in the claims. 
     Example 1 
     Genes Expression Differences Between Intra-Abdominal And Subcutaneous Adipose Tissue of Mice 
     Several studies have reported differences in gene expression (Atzmon et al, (2002) Horm Metab Res 34, 622-8; Linder et al., (2004) J Lipid Res 45, 148-54; Vohl et al., (2004) Obes Res 12, 1217-22; and von Eyben et al., (2004) Ann N Y Acad Sci 1030, 508-36) and proliferative capacity (Djian et al., (1983) J Clin Invest 72, 1200-8; Adams et al., (1997) J Clin Invest 100, 3149-53; Kirkland et al., (1990) Am J Physiol 258, C206-10; Hauner and Entenmann, (1991) Int J Obes 15, 121-6; Tchkonia et al., (2002) Am J Physiol Regul Integr Comp Physiol 282, RI 286-96; and Tchkonia et al., (2005) Am J Physiol Endocrinol Metab 288, E267-77) between fat taken from different depots in rodents and humans suggesting that genetic pro n g could affect specific adipose depot development. 
     To address this hypothesis, we performed gene expression analysis of both adipocytes (Ad) and stromovascular fraction (SVF) containing preadipocytes taken from subcutaneous (flank) fat and intra-abdominal (epididymal) fat. 
     Embryonic Development and Pattern Specification Set of Genes 
     A priori, we created a set of genes involve in embryonic development and pattern specification, using Gene Ontology Biological Processes annotations. The NetAffx™ Analysis Center (available on the world wide web at affymetrix.com), was queried for genes annotated for “embryonic development,” “pattern specification,” “pattern formation,” “mesoderm formation,” and/or “organogenesis.” The list obtained was then scrutinized and updated by review of the relevant literature for data implicating each gene family in directing embryonic development (e.g., BMP family, Frizzled homolog family, Hox family, or Pax family). A final set of 198 genes (254 probesets) with strong literature support was thus chosen to evaluate the enrichment in genes involve in embryonic development and pattern specification. 
     Adipose Tissue, Isolated Adipocytes and Stromovascular Fractions (SVF) and RNA Extraction 
     For analysis of adipose tissue, Six 6 to 7 weeks old C57b1/6 males were sacrificed and epididymal and flank subcutaneous adipose tissue were removed, washed with PBS, and immediately subjected to RNA extraction. To obtain purified cell fractions, ten 6- to 7-weeks old C57b1/6 males were sacrificed and epididymal and flank subcutaneous adipose tissue were removed under sterile conditions. Tissues from each depot were pooled, minced and digested with 1 mg/ml collagenase for 45 minutes at 37° C. in Dulbecco&#39;s modified Eagle&#39;s medium/Hamn&#39;s F-12 1:1 (DMEM/F 12), containing 1% BSA and antibiotics (penicillin 100 U/ml, streptomycin 0.1 mg/ml, fungizone 2.5 μg/ml and gentamicin 50 μg/ml). Digested tissues were filtered through sterile 150 μm nylon mesh and centrifuged at 250×g for 5 minutes. The floating fraction consisting of pure isolated adipocytes was then removed and washes 2 more times before proceeding to RNA extraction. The pellet, representing the stromovascular fraction containing preadipocytes and other cell types, was resuspended in erythrocyte lysis buffer consisting of 154 mM NH 4 Cl, 10 mM KHCO 3  and 0.1 mM EDTA for 10 minutes. The cell suspension was centrifuged at 500×g for 5 minutes and then resuspended in a culture medium consisting DMEM/F12, 10% fetal calf serum (FCS) and antibiotics. This cell suspension was filtered through a 25 μm sterile nylon mesh before being plated on 10 cm plate at 60,000 cells per cm 2 . 16 hours after plating, cells were extensively washed with PBS then subjected to RNA extraction. 
     Sample Preparation for Microarrays 
     RNA from adipose tissue, isolated adipocytes and stromovascular fractions were isolated using RNeasy kit (Qiagen). Double-stranded cDNA synthesis was reverse transcribed from 15 μg of isolated mRNA using the SuperScript Choice system (Invitrogen) using an oligo(dT) primer containing a T7 RNA polymerase promoter site. Double-stranded cDNA was purified with Phase Lock Gel (Eppendorf). Biotin-labeled cRNA was transcribed using a BioArray™ RNA transcript labeling kit (Enzo). A hybridization mixture containing 15 μg of biotinylated cRNA, adjusted for possible carryover of residual total RNA, was prepared and hybridized to mouse Affymetrix MG-U74A-v2 chips. The chips were washed, scanned, and analyzed with GeneChip® MAS Microarray Suite Software V. 5.0. For each group (epididymal and subcutaneous), 3 chips, each representing a pool of RNA from 10 mice, was analyzed used. All chips were subjected to global scaling to a target intensity of 1500 to take into account the inherent differences between the chips and their hybridization efficiencies. 
     Microarray Analysis 
     The 8017 probesets on the murine U74Av2 microarray representing 6174 genes with annotations for Gene Ontology biologic processes (available on the internet at affymetrix.com, accessed Nov. 13, 2005) were considered for analysis. To obtain a list of genes with a conjoint differential expression between the two tissue beds, we selected genes that passed two independent filters of significance. The first filter screened for genes with evidence of independent differential expression for both tissues types between tissue beds by selecting those genes with significance levels of p&lt;0.05 using Student&#39;s t-test for both cell types (Ae versus Ase; Se versus Ssc). The second filter used a single test statistic to selected genes that exhibited concordant and significant differential expression in both the adipocytes and stromovascular fractions between epididymal and subcutaneous adipose tissues. To this end, we used a combined test statistic T Δ+Δ =[(S sc −S e )+(A sc −A e )]/SD, where S represents the expression value in the stromovascular fraction, A adipocytes, subscript sc subcutaneous depot subscript e epididymal depot, and SD the sums of the four standard deviations. T Δ+Δ  is expected to be zero when there is no difference in expression between tissue depots, and non-zero if one cell-type experienced differential expression between tissue depots. Congruent changes in expression between tissue depots for both cell types will lead to even greater values of T Δ+Δ , whereas changes of opposite direction will cancel each other out. By using this single test statistic, we were able to determine the positive false discovery rate (pFDR) (Mauriege et al., (1993) Eur J Clin Invest 23, 729-40), thus determining the probability of significant joint differential regulation corrected for multiple hypothesis testing. 
     The Affymetrix U74Av2 microarrays were used, with 8017 probesets representing 6174 different annotated genes (www.affymetrix.com, Nov. 13, 2005) ( FIG. 1B ). Of these, 197 genes were found to have conjoint differential expression in both cell fractions between the two tissue beds using stringent statistical criteria with a two tailed t-test value for both cell fractions &lt;0.05 and a positive False Discovery Rate value &lt;0.05 (see Table 1). This list was assessed against an a priori set of 198 annotated genes involved in embryonic development and pattern specification on the array (see Table 2). Twelve of these developmental genes were found among the differentially expressed genes, representing a 1.9-fold enrichment (=0.006) compared to the 6174 annotated genes on the array (Table 1). 
     Among these 12 genes, seven genes had higher levels of expression in intra-abdominal a epididymal SVF and/or adipocytes (Nr2f1, Thbd, HoxA5, HoxC8, Gpc4, Hrmt112, and Vdr) and five genes had higher levels of expression in subcutaneous SVF and/or adipocytes (Tbx15, Shox2, En1, Slpr2 and HoxC9). Of the seven genes from intra-abdominal group, we decided to focus our analysis on the five most significant genes, including two Homeobox genes, HoxA5 and HoxC8; Nr2f1, nuclear receptor subfamily 2 group F member 1, also known as COUP-TFI, an orphan member of the steroid receptor superfamily thought to be involved in organogenesis (Pereira et al., (199S) J Steroid Biochem Mol Biol 53, 503-8); glypican 4 (Gpc4), a cell surface heparan sulfate proteoglycan involved in cell division and growth regulation (De Cat and David, (2001) Semin Cell Dev Biol 12, 117-25); and thrombomodulin (Thbd), a surface glycoprotein of endothelial and placental cells (Weiler and Isermann, (2003) J Thromb Haemost 1, 1515-24). All five genes from subcutaneous group of genes including the Homeobox gene HoxC9; short stature Homeobox 2 (Shox2) a transcription factor with homeodomain expressed during embryonic development (Blaschke et al., (1998) Proc Natl Acad Sci USA 95, 2406-11); Thox-15 (Tbx15), a transcription factor involved in craniofacial and limb development in the mouse (Singh et al., (2005) Mech Dev 122, 131-44); engrailed 1 (En1), the mouse homologue of a  Drosophila  patterning gene (Joyner and Martin, (1987) Genes Dev 1, 29-38); and secreted frizzled-related protein 2 (Sfrp2), a soluble modulator of Wnt signaling (Leimeister et al., (1998) Mech Dev 75, 29-42), were also studied. 
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Genes Showing Differential Expression in Adipoctyes 
               
               
                 and Stromovascular Fraction of Adipose Tissue. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Mean 
                 Mean 
                 p value 
                 Mean 
                 Mean 
                 p value 
               
               
                 Gene ID 
                 Probeset ID 
                 Ae 
                 Asc 
                 Ae vs Asc 
                 Se 
                 Ssc 
                 Se vs Ssc 
               
               
                   
               
               
                 AE000663 
                 92712_at 
                 99.3 
                 389.9 
                 0.0171 
                 241.8 
                 359.6 
                 0.0039 
               
               
                 AA675604 
                 104544_at 
                 162.4 
                 773.7 
                 0.0469 
                 129.7 
                 838.2 
                 0.0012 
               
               
                 AI849271 
                 95064_at 
                 50538.9 
                 77559.2 
                 0.0285 
                 7387.2 
                 4569.3 
                 0.0123 
               
               
                 J04946 
                 160927_at 
                 219.1 
                 662.0 
                 0.0364 
                 314.5 
                 2798.3 
                 0.0020 
               
               
                 AI838021 
                 97456_at 
                 1398.1 
                 2474.9 
                 0.0201 
                 1723.4 
                 2838.2 
                 0.0039 
               
               
                 AF045887 
                 101887_at 
                 16339.4 
                 2185.5 
                 0.0078 
                 88.7 
                 754.0 
                 0.0021 
               
               
                 AB027125 
                 95015_at 
                 2059.1 
                 790.5 
                 0.0047 
                 652.9 
                 148.7 
                 0.0149 
               
               
                 M74570 
                 100068_at 
                 17238.1 
                 8658.5 
                 0.0063 
                 25048.8 
                 12039.6 
                 0.0076 
               
               
                 AW123269 
                 96784_at 
                 383.4 
                 72.0 
                 0.0016 
                 3239.2 
                 640.8 
                 0.0096 
               
               
                 AV003419 
                 161703_f_at 
                 44613.5 
                 26734.9 
                 0.0272 
                 33384.2 
                 12585.7 
                 0.0010 
               
               
                 M14044 
                 100569_at 
                 98848.5 
                 53546.4 
                 0.0099 
                 30093.7 
                 18292.6 
                 0.0384 
               
               
                 AJ002390 
                 97529_at 
                 1219.7 
                 3507.0 
                 0.0336 
                 477.5 
                 1645.1 
                 0.0123 
               
               
                 M97216 
                 93498_s_at 
                 24056.5 
                 18497.4 
                 0.0046 
                 7375.0 
                 4106.1 
                 0.0248 
               
               
                 X82648 
                 93592_at 
                 87.8 
                 335.6 
                 0.0094 
                 95.2 
                 274.4 
                 0.0287 
               
               
                 D87901 
                 160082_s_at 
                 9205.1 
                 5438.4 
                 0.0211 
                 18123.6 
                 12870.6 
                 0.0026 
               
               
                 AI852332 
                 99497_at 
                 804.8 
                 1164.0 
                 0.0319 
                 583.5 
                 1371.2 
                 0.0103 
               
               
                 AI846773 
                 104315_at 
                 2814.7 
                 1389.7 
                 0.0376 
                 6232.6 
                 1996.7 
                 0.0007 
               
               
                 M63725 
                 100984_at 
                 1498.0 
                 1162.9 
                 0.0153 
                 3211.6 
                 5035.8 
                 0.0367 
               
               
                 U13840 
                 92603_at 
                 7219.7 
                 5807.5 
                 0.0271 
                 7956.1 
                 4528.0 
                 0.0015 
               
               
                 X01838 
                 93088_at 
                 68009.1 
                 78627.3 
                 0.0219 
                 40904.2 
                 64767.4 
                 0.0072 
               
               
                 X55573 
                 102727_at 
                 119.3 
                 370.4 
                 0.0390 
                 8004.2 
                 2198.5 
                 0.0000 
               
               
                 D83745 
                 96146_at 
                 874.5 
                 1375.1 
                 0.0064 
                 7989.1 
                 3765.1 
                 0.0165 
               
               
                 X06454 
                 103033_at 
                 18499.6 
                 33207.4 
                 0.0016 
                 4763.7 
                 42308.8 
                 0.0000 
               
               
                 M19381 
                 96522_at 
                 40446.4 
                 28714.6 
                 0.0090 
                 20940.0 
                 12234.6 
                 0.0174 
               
               
                 M27844 
                 93293_at 
                 27546.3 
                 20459.3 
                 0.0176 
                 49178.8 
                 40506.3 
                 0.0259 
               
               
                 AI842328 
                 92632_at 
                 4473.1 
                 3046.9 
                 0.0244 
                 8109.3 
                 4285.6 
                 0.0121 
               
               
                 U16740 
                 93499_at 
                 5064.7 
                 4173.5 
                 0.0313 
                 9309.7 
                 8050.9 
                 0.0080 
               
               
                 U16741 
                 98127_at 
                 5755.6 
                 3678.1 
                 0.0107 
                 5109.3 
                 3526.1 
                 0.0067 
               
               
                 AI747654 
                 160280_at 
                 50615.1 
                 32157.4 
                 0.0124 
                 8644.3 
                 3761.3 
                 0.0018 
               
               
                 AB023418 
                 92459_at 
                 682.8 
                 2312.4 
                 0.0464 
                 624.5 
                 33115.2 
                 0.0001 
               
               
                 X66032 
                 94294_at 
                 998.2 
                 1429.9 
                 0.0088 
                 3392.3 
                 2047.4 
                 0.0008 
               
               
                 AW047630 
                 99535_at 
                 18919.9 
                 10694.1 
                 0.0333 
                 3717.8 
                 5383.2 
                 0.0237 
               
               
                 AI847784 
                 160358_at 
                 680.0 
                 1124.7 
                 0.0281 
                 252.6 
                 450.5 
                 0.0295 
               
               
                 L78075 
                 94105_at 
                 9941.6 
                 7597.7 
                 0.0006 
                 12300.8 
                 9734.5 
                 0.0140 
               
               
                 M31131 
                 102852_at 
                 80.2 
                 234.1 
                 0.0498 
                 1749.1 
                 814.7 
                 0.0161 
               
               
                 AI854020 
                 96346_at 
                 71828.6 
                 45731.2 
                 0.0032 
                 623.5 
                 2584.8 
                 0.0052 
               
               
                 AV336987 
                 161941_r_at 
                 2919.9 
                 4189.9 
                 0.0194 
                 3509.7 
                 4786.5 
                 0.0204 
               
               
                 AI838398 
                 96725_at 
                 1119.0 
                 1414.1 
                 0.0235 
                 2275.2 
                 3315.1 
                 0.0079 
               
               
                 Y15163 
                 101973_at 
                 6854.0 
                 3597.3 
                 0.0196 
                 8237.5 
                 3678.1 
                 0.0014 
               
               
                 Z18272 
                 93517_at 
                 15077.4 
                 8457.4 
                 0.0091 
                 3323.0 
                 6487.4 
                 0.0035 
               
               
                 AF017175 
                 93320_at 
                 6518.6 
                 3200.5 
                 0.0087 
                 8312.1 
                 3186.6 
                 0.0001 
               
               
                 AV013428 
                 162308_f_at 
                 1503.8 
                 2208.4 
                 0.0028 
                 4465.9 
                 2218.9 
                 0.0080 
               
               
                 AI837625 
                 160065_s_at 
                 4354.7 
                 2016.4 
                 0.0022 
                 17483.3 
                 3532.9 
                 0.0000 
               
               
                 U49385 
                 160652_at 
                 1599.6 
                 1234.2 
                 0.0155 
                 3356.0 
                 2021.9 
                 0.0020 
               
               
                 U74683 
                 101019_at 
                 2225.8 
                 1023.3 
                 0.0072 
                 1143.9 
                 251.9 
                 0.0022 
               
               
                 AW061318 
                 97255_at 
                 2692.1 
                 1369.1 
                 0.0436 
                 3647.5 
                 1727.0 
                 0.0201 
               
               
                 U27267 
                 98772_at 
                 147.8 
                 43.9 
                 0.0462 
                 246.4 
                 789.6 
                 0.0131 
               
               
                 X78445 
                 99979_at 
                 1289.4 
                 117.7 
                 0.0299 
                 30354.7 
                 15883.0 
                 0.0033 
               
               
                 D63679 
                 103617_at 
                 276.9 
                 472.4 
                 0.0383 
                 374.1 
                 608.6 
                 0.0315 
               
               
                 AB026432 
                 95683_g_at 
                 8997.6 
                 7136.2 
                 0.0051 
                 20606.4 
                 16879.8 
                 0.0114 
               
               
                 Z38015 
                 93431_at 
                 12219.9 
                 9890.5 
                 0.0197 
                 14812.4 
                 7269.5 
                 0.0011 
               
               
                 AW060270 
                 97868_at 
                 3304.7 
                 4534.0 
                 0.0031 
                 3134.2 
                 3784.0 
                 0.0215 
               
               
                 M76131 
                 97559_at 
                 21077.2 
                 16056.3 
                 0.0358 
                 23817.2 
                 20575.5 
                 0.0386 
               
               
                 U57686 
                 96195_at 
                 878.9 
                 1414.4 
                 0.0453 
                 1206.9 
                 2448.8 
                 0.0009 
               
               
                 AW049716 
                 101841_at 
                 805.7 
                 380.1 
                 0.0329 
                 3471.5 
                 5432.1 
                 0.0236 
               
               
                 AJ006587 
                 94252_at 
                 10301.5 
                 7696.0 
                 0.0353 
                 10657.9 
                 8904.5 
                 0.0260 
               
               
                 X98471 
                 97426_at 
                 50456.2 
                 27341.7 
                 0.0044 
                 19625.7 
                 9467.9 
                 0.0046 
               
               
                 L12703 
                 96523_at 
                 53.1 
                 422.9 
                 0.0128 
                 1005.3 
                 2116.3 
                 0.0083 
               
               
                 M29961 
                 102373_at 
                 6763.2 
                 2915.9 
                 0.0006 
                 670.2 
                 1147.2 
                 0.0259 
               
               
                 J02700 
                 104174_at 
                 26.6 
                 93.1 
                 0.0347 
                 662.5 
                 104.4 
                 0.0062 
               
               
                 AW122933 
                 97317_at 
                 21426.3 
                 13197.2 
                 0.0039 
                 297.4 
                 1848.3 
                 0.0005 
               
               
                 AW061222 
                 97517_at 
                 1934.3 
                 2521.4 
                 0.0312 
                 1258.9 
                 1649.7 
                 0.0420 
               
               
                 U41739 
                 97498_at 
                 16061.1 
                 12045.1 
                 0.0257 
                 16926.6 
                 1944.8 
                 0.0029 
               
               
                 DI6215 
                 101991_at 
                 9522.8 
                 13037.1 
                 0.0311 
                 263.6 
                 1443.3 
                 0.0017 
               
               
                 AF017128 
                 99835_at 
                 1185.8 
                 373.0 
                 0.0478 
                 1467.6 
                 3371.1 
                 0.0025 
               
               
                 AI839918 
                 93270_at 
                 4261.9 
                 3501.9 
                 0.0173 
                 10705.2 
                 7081.3 
                 0.0335 
               
               
                 AB000096 
                 102789_at 
                 694.4 
                 1140.3 
                 0.0291 
                 1799.9 
                 729.8 
                 0.0001 
               
               
                 L41631 
                 102651_at 
                 278.3 
                 750.8 
                 0.0081 
                 601.3 
                 830.7 
                 0.0369 
               
               
                 U15012 
                 99108_s_at 
                 26654.2 
                 19789.5 
                 0.0396 
                 1414.8 
                 2202.9 
                 0.0108 
               
               
                 AI153412 
                 104412_at 
                 8093.8 
                 5438.8 
                 0.0124 
                 2394.2 
                 625.0 
                 0.0050 
               
               
                 X83577 
                 102886_at 
                 2522.8 
                 1687.2 
                 0.0102 
                 7312.0 
                 2151.0 
                 0.0090 
               
               
                 D50430 
                 98984_f_at 
                 4526.9 
                 7135.8 
                 0.0331 
                 851.3 
                 1110.8 
                 0.0061 
               
               
                 AB003502 
                 93727_at 
                 6809.2 
                 4002.5 
                 0.0280 
                 7801.1 
                 6419.4 
                 0.0229 
               
               
                 AF043220 
                 94296_s_at 
                 2002.8 
                 1504.9 
                 0.0173 
                 941.1 
                 680.0 
                 0.0237 
               
               
                 M69069 
                 97540_f_at 
                 56632.0 
                 84722.1 
                 0.0060 
                 19345.1 
                 48703.0 
                 0.0026 
               
               
                 X52490 
                 101886_f_at 
                 47481.0 
                 67094.4 
                 0.0037 
                 18901.1 
                 50653.5 
                 0.0004 
               
               
                 V00746 
                 93120_f_at 
                 66239.3 
                 96624.8 
                 0.0083 
                 25468.5 
                 59120.4 
                 0.0001 
               
               
                 X16426 
                 101898_s_at 
                 3484.2 
                 14555.1 
                 0.0139 
                 764.4 
                 3709.8 
                 0.0000 
               
               
                 Y00629 
                 98472_at 
                 566.5 
                 1182.3 
                 0.0013 
                 1837.9 
                 3367.8 
                 0.0001 
               
               
                 U05837 
                 94840_at 
                 1452.0 
                 2031.7 
                 0.0150 
                 2229.4 
                 6725.3 
                 0.0001 
               
               
                 AF077659 
                 103833_at 
                 7260.1 
                 3440.7 
                 0.0113 
                 428.0 
                 169.9 
                 0.0191 
               
               
                 Y00208 
                 103086_at 
                 1604.8 
                 837.8 
                 0.0305 
                 1657.3 
                 242.6 
                 0.0000 
               
               
                 X07439 
                 93378_at 
                 2484.5 
                 1597.2 
                 0.0374 
                 3351.3 
                 1144.9 
                 0.0003 
               
               
                 X55318 
                 92891_f_at 
                 674.4 
                 1189.3 
                 0.0042 
                 748.2 
                 564.6 
                 0.0357 
               
               
                 U44389 
                 93351_at 
                 930.5 
                 425.9 
                 0.0401 
                 2136.2 
                 641.6 
                 0.0024 
               
               
                 AI837110 
                 96696_at 
                 1628.4 
                 990.7 
                 0.0287 
                 3705.9 
                 2379.7 
                 0.0369 
               
               
                 Y15733 
                 94177_at 
                 374.9 
                 158.7 
                 0.0274 
                 668.6 
                 461.1 
                 0.0181 
               
               
                 AA762325 
                 97859_at 
                 2627.2 
                 1327.8 
                 0.0086 
                 5876.8 
                 3991.2 
                 0.0105 
               
               
                 M21065 
                 102401_at 
                 9524.6 
                 17803.2 
                 0.0055 
                 793.0 
                 1186.8 
                 0.0367 
               
               
                 Y11460 
                 94826_at 
                 2244.9 
                 1790.8 
                 0.0016 
                 2332.9 
                 3410.1 
                 0.0007 
               
               
                 M90365 
                 104121_at 
                 3445.4 
                 1685.8 
                 0.0010 
                 1314.7 
                 447.7 
                 0.0009 
               
               
                 AB013345 
                 102020_at 
                 501.0 
                 1359.0 
                 0.0132 
                 20.0 
                 15.6 
                 0.0472 
               
               
                 U36340 
                 100010_at 
                 751.9 
                 652.0 
                 0.0488 
                 1684.7 
                 1343.9 
                 0.0477 
               
               
                 AW047023 
                 96010_at 
                 3542.9 
                 2569.8 
                 0.0430 
                 4870.3 
                 4120.3 
                 0.0186 
               
               
                 AF034745 
                 102038_at 
                 138.8 
                 212.6 
                 0.0336 
                 117.7 
                 258.7 
                 0.0016 
               
               
                 M63335 
                 160083_at 
                 59754.7 
                 40987.4 
                 0.0078 
                 5915.5 
                 11405.0 
                 0.0019 
               
               
                 U27195 
                 92401_at 
                 9509.6 
                 5737.5 
                 0.0051 
                 632.4 
                 906.3 
                 0.0233 
               
               
                 D86232 
                 93077_s_at 
                 12075.9 
                 21116.2 
                 0.0363 
                 7720.2 
                 18785.1 
                 0.0008 
               
               
                 AI848045 
                 93749_at 
                 2311.3 
                 1325.5 
                 0.0049 
                 4965.7 
                 10727.1 
                 0.0004 
               
               
                 AI317205 
                 103020_s_at 
                 1197.6 
                 1453.4 
                 0.0467 
                 818.0 
                 1057.5 
                 0.0233 
               
               
                 Y13439 
                 92323_at 
                 596.2 
                 978.5 
                 0.0476 
                 1088.5 
                 1708.2 
                 0.0096 
               
               
                 AI844810 
                 103416_at 
                 21093.8 
                 11355.8 
                 0.0004 
                 9413.9 
                 13726.7 
                 0.0088 
               
               
                 AB005662 
                 160880_at 
                 678.6 
                 1004.7 
                 0.0150 
                 868.2 
                 1431.0 
                 0.0162 
               
               
                 AF072240 
                 104340_at 
                 1723.0 
                 659.4 
                 0.0228 
                 1693.7 
                 858.1 
                 0.0494 
               
               
                 AI853261 
                 160458_at 
                 8292.3 
                 5080.0 
                 0.0082 
                 815.0 
                 325.3 
                 0.0001 
               
               
                 AI841279 
                 100539_at 
                 1566.2 
                 851.8 
                 0.0233 
                 2153.9 
                 779.6 
                 0.0001 
               
               
                 X66402 
                 98833_at 
                 179.5 
                 622.3 
                 0.0475 
                 14273.8 
                 68072.2 
                 0.0006 
               
               
                 J02652 
                 101082_at 
                 47789.2 
                 63641.8 
                 0.0269 
                 8250.1 
                 6163.1 
                 0.0039 
               
               
                 AB004879 
                 103653_at 
                 555.5 
                 167.3 
                 0.0132 
                 951.7 
                 597.1 
                 0.0107 
               
               
                 AI255271 
                 102096_f_at 
                 128.0 
                 9573.7 
                 0.0226 
                 50.3 
                 149.4 
                 0.0011 
               
               
                 M16359 
                 101910_f_at 
                 183.1 
                 11635.4 
                 0.0321 
                 36.7 
                 68.7 
                 0.0407 
               
               
                 X51829 
                 160463_at 
                 2434.6 
                 3653.3 
                 0.0215 
                 1268.8 
                 1630.9 
                 0.0278 
               
               
                 AI648850 
                 100828_at 
                 1041.0 
                 1659.4 
                 0.0290 
                 650.4 
                 1261.2 
                 0.0067 
               
               
                 AI117835 
                 93482_at 
                 13090.5 
                 6705.6 
                 0.0002 
                 37600.0 
                 7683.1 
                 0.0020 
               
               
                 U96723 
                 95506_at 
                 2031.0 
                 906.5 
                 0.0336 
                 3157.4 
                 2087.1 
                 0.0244 
               
               
                 U81453 
                 94713_at 
                 918.9 
                 1198.3 
                 0.0119 
                 2868.2 
                 3548.0 
                 0.0141 
               
               
                 X61449 
                 98587_at 
                 4299.8 
                 2754.7 
                 0.0286 
                 7851.0 
                 3334.8 
                 0.0067 
               
               
                 AW125874 
                 95070_at 
                 1143.4 
                 796.7 
                 0.0190 
                 5282.0 
                 3996.4 
                 0.0017 
               
               
                 U83148 
                 102955_at 
                 3785.4 
                 1707.8 
                 0.0075 
                 1632.7 
                 1039.5 
                 0.0212 
               
               
                 Y07688 
                 101930_at 
                 8742.6 
                 6157.7 
                 0.0270 
                 8430.9 
                 6011.9 
                 0.0193 
               
               
                 AB017202 
                 93563_s_at 
                 3536.5 
                 1703.8 
                 0.0051 
                 29717.3 
                 17043.2 
                 0.0181 
               
               
                 Z49204 
                 99009_at 
                 1892.7 
                 964.1 
                 0.0173 
                 5358.6 
                 2207.2 
                 0.0003 
               
               
                 AI839690 
                 103922_f_at 
                 864.2 
                 519.2 
                 0.0464 
                 4941.0 
                 2840.9 
                 0.0113 
               
               
                 X74134 
                 102715_at 
                 551.1 
                 101.1 
                 0.0057 
                 1383.2 
                 289.9 
                 0.0004 
               
               
                 AA645293 
                 97977_at 
                 733.1 
                 1220.0 
                 0.0057 
                 1199.2 
                 2054.2 
                 0.0021 
               
               
                 AF089751 
                 95586_at 
                 1077.8 
                 1530.7 
                 0.0094 
                 2404.7 
                 4921.1 
                 0.0000 
               
               
                 AJ009823 
                 101712_at 
                 997.9 
                 1810.0 
                 0.0270 
                 793.7 
                 1259.4 
                 0.0080 
               
               
                 AI846025 
                 95470_at 
                 4077.9 
                 2298.9 
                 0.0217 
                 1407.0 
                 1702.8 
                 0.0441 
               
               
                 AB006758 
                 102280_at 
                 756.2 
                 294.5 
                 0.0182 
                 1373.0 
                 497.7 
                 0.0009 
               
               
                 X57337 
                 93349_at 
                 1721.3 
                 4735.5 
                 0.0042 
                 23473.4 
                 47164.8 
                 0.0042 
               
               
                 D50060 
                 101196_at 
                 879.6 
                 1671.0 
                 0.0052 
                 4967.6 
                 1661.0 
                 0.0063 
               
               
                 AA755004 
                 96831_at 
                 63.5 
                 374.9 
                 0.0161 
                 1939.4 
                 5034.1 
                 0.0004 
               
               
                 AI842259 
                 92810_at 
                 966.4 
                 385.0 
                 0.0178 
                 6964.0 
                 3660.8 
                 0.0010 
               
               
                 AF053367 
                 100554_at 
                 1740.5 
                 1093.8 
                 0.0134 
                 10364.4 
                 5104.7 
                 0.0130 
               
               
                 U44088 
                 160829_at 
                 8260.0 
                 13438.1 
                 0.0111 
                 6162.8 
                 10902.3 
                 0.0025 
               
               
                 AA607557 
                 161034_at 
                 284.8 
                 746.2 
                 0.0205 
                 475.5 
                 656.6 
                 0.0177 
               
               
                 U85711 
                 104580_at 
                 1760.7 
                 893.9 
                 0.0033 
                 1997.4 
                 1423.8 
                 0.0040 
               
               
                 AW047139 
                 96774_at 
                 2483.6 
                 1584.8 
                 0.0376 
                 5635.3 
                 4697.2 
                 0.0109 
               
               
                 Z38110 
                 102395_at 
                 14731.0 
                 9813.7 
                 0.0169 
                 33630.2 
                 18940.4 
                 0.0002 
               
               
                 AW123013 
                 99183_at 
                 7021.4 
                 5762.2 
                 0.0129 
                 6489.0 
                 4811.7 
                 0.0122 
               
               
                 AF093857 
                 100622_at 
                 19772.8 
                 10598.1 
                 0.0067 
                 15049.0 
                 28212.0 
                 0.0003 
               
               
                 AF093853 
                 100332_s_at 
                 9035.9 
                 4555.0 
                 0.0091 
                 9217.0 
                 19732.5 
                 0.0012 
               
               
                 AW122197 
                 96852_at 
                 9116.7 
                 6581.3 
                 0.0162 
                 16038.7 
                 13215.3 
                 0.0216 
               
               
                 AV353694 
                 161446_r_at 
                 5368.4 
                 8850.8 
                 0.0445 
                 6341.9 
                 7869.5 
                 0.0091 
               
               
                 AW122030 
                 96295_at 
                 14317.5 
                 8059.2 
                 0.0050 
                 11078.7 
                 7195.3 
                 0.0019 
               
               
                 U22033 
                 102791_at 
                 1464.2 
                 4114.7 
                 0.0102 
                 1964.7 
                 3551.1 
                 0.0009 
               
               
                 D44456 
                 93085_at 
                 923.8 
                 3031.4 
                 0.0156 
                 280.9 
                 1003.0 
                 0.0115 
               
               
                 AI845915 
                 104100_at 
                 43869.2 
                 36308.4 
                 0.0448 
                 9141.5 
                 4899.8 
                 0.0138 
               
               
                 M89777 
                 97415_at 
                 4734.7 
                 3200.4 
                 0.0127 
                 1449.5 
                 1776.4 
                 0.0455 
               
               
                 X89650 
                 99587_at 
                 3208.4 
                 2386.6 
                 0.0365 
                 3173.9 
                 2756.2 
                 0.0164 
               
               
                 AI844445 
                 102117_at 
                 1345.9 
                 594.0 
                 0.0348 
                 1178.8 
                 632.5 
                 0.0011 
               
               
                 X57277 
                 101555_at 
                 31407.3 
                 18445.6 
                 0.0158 
                 42855.4 
                 31108.0 
                 0.0023 
               
               
                 D64162 
                 102649_s_at 
                 104.9 
                 464.9 
                 0.0022 
                 1754.7 
                 829.2 
                 0.0101 
               
               
                 AI847564 
                 93070_at 
                 1324.4 
                 957.6 
                 0.0436 
                 3290.6 
                 2617.0 
                 0.0430 
               
               
                 AB016424 
                 96041_at 
                 7605.2 
                 3592.8 
                 0.0027 
                 10082.0 
                 7170.8 
                 0.0128 
               
               
                 AW046449 
                 96207_at 
                 2836.5 
                 1945.1 
                 0.0249 
                 13237.0 
                 7607.3 
                 0.0141 
               
               
                 AI048434 
                 160518_at 
                 5922.5 
                 4298.2 
                 0.0188 
                 4844.0 
                 4013.7 
                 0.0485 
               
               
                 AF014371 
                 101112_g_at 
                 14325.1 
                 10492.6 
                 0.0392 
                 13158.0 
                 9154.3 
                 0.0131 
               
               
                 AW121012 
                 100509_at 
                 2024.6 
                 1360.7 
                 0.0215 
                 3508.4 
                 2112.6 
                 0.0082 
               
               
                 U58513 
                 98504_at 
                 2947.2 
                 1543.6 
                 0.0085 
                 11648.0 
                 6191.0 
                 0.0076 
               
               
                 M83218 
                 103448_at 
                 1075.6 
                 480.1 
                 0.0009 
                 272.8 
                 492.9 
                 0.0478 
               
               
                 X03505 
                 102712_at 
                 13920.3 
                 5441.6 
                 0.0300 
                 61929.6 
                 102890.2 
                 0.0061 
               
               
                 L10244 
                 96657_at 
                 9701.0 
                 6761.9 
                 0.0170 
                 7749.4 
                 17947.1 
                 0.0008 
               
               
                 AB008553 
                 101389_at 
                 3358.1 
                 4064.3 
                 0.0402 
                 14319.9 
                 9631.1 
                 0.0220 
               
               
                 M21285 
                 94057_g_at 
                 231696.5 
                 305128.6 
                 0.0144 
                 7982.8 
                 19207.9 
                 0.0023 
               
               
                 U88567 
                 93503_at 
                 281.2 
                 1510.6 
                 0.0405 
                 621.2 
                 6317.6 
                 0.0000 
               
               
                 U66918 
                 99042_s_at 
                 282.1 
                 2457.0 
                 0.0004 
                 397.2 
                 3622.3 
                 0.0023 
               
               
                 AJ243651 
                 100373_at 
                 166.5 
                 311.5 
                 0.0371 
                 131.9 
                 176.4 
                 0.0347 
               
               
                 AF004666 
                 99524_at 
                 611.6 
                 265.7 
                 0.0100 
                 3396.8 
                 996.2 
                 0.0041 
               
               
                 AI839882 
                 94034_at 
                 2871.2 
                 1875.4 
                 0.0201 
                 4247.6 
                 1982.7 
                 0.0009 
               
               
                 U88328 
                 92232_at 
                 3605.6 
                 17509.2 
                 0.0013 
                 1969.1 
                 4618.8 
                 0.0094 
               
               
                 AJ005567 
                 95794_f_at 
                 1233.3 
                 2070.9 
                 0.0067 
                 3158.0 
                 5385.1 
                 0.0302 
               
               
                 AI837107 
                 103504_at 
                 1038.7 
                 1226.3 
                 0.0056 
                 2045.5 
                 1207.7 
                 0.0052 
               
               
                 U47323 
                 100952_at 
                 9903.8 
                 3763.6 
                 0.0424 
                 1916.9 
                 1387.8 
                 0.0283 
               
               
                 AI842665 
                 93327_at 
                 2700.0 
                 1935.9 
                 0.0180 
                 2745.0 
                 2191.4 
                 0.0287 
               
               
                 AF041822 
                 102256_at 
                 20.8 
                 255.0 
                 0.0012 
                 23.1 
                 727.1 
                 0.0124 
               
               
                 U86137 
                 93367_at 
                 755.9 
                 153.3 
                 0.0140 
                 628.4 
                 495.9 
                 0.0425 
               
               
                 L19932 
                 92877_at 
                 501.6 
                 735.6 
                 0.0447 
                 93.2 
                 353.1 
                 0.0137 
               
               
                 X14432 
                 104601_at 
                 2245.4 
                 861.4 
                 0.0094 
                 5919.2 
                 1878.5 
                 0.0005 
               
               
                 M62470 
                 160469_at 
                 8011.5 
                 1387.4 
                 0.0209 
                 41141.3 
                 26162.1 
                 0.0052 
               
               
                 AI849587 
                 95465_s_at 
                 743.1 
                 1129.6 
                 0.0122 
                 2896.5 
                 1034.0 
                 0.0491 
               
               
                 AI852433 
                 104071_at 
                 3352.1 
                 2358.6 
                 0.0131 
                 5282.7 
                 3615.1 
                 0.0487 
               
               
                 L31777 
                 99566_at 
                 27393.0 
                 23196.3 
                 0.0026 
                 27201.0 
                 16484.4 
                 0.0005 
               
               
                 M28729 
                 100343_f_at 
                 94370.3 
                 50995.0 
                 0.0069 
                 38286.9 
                 19310.8 
                 0.0287 
               
               
                 M13441 
                 101543_f_at 
                 160632.1 
                 76299.2 
                 0.0013 
                 59543.9 
                 34148.4 
                 0.0377 
               
               
                 M28739 
                 94835_f_at 
                 7670.9 
                 4789.0 
                 0.0080 
                 17788.7 
                 9599.6 
                 0.0037 
               
               
                 X04663 
                 94788_f_at 
                 18550.8 
                 11564.0 
                 0.0173 
                 28376.4 
                 17148.7 
                 0.0001 
               
               
                 AI840882 
                 95696_at 
                 21807.0 
                 14814.2 
                 0.0322 
                 10205.9 
                 7138.5 
                 0.0036 
               
               
                 AW046479 
                 102279_at 
                 643.6 
                 1293.8 
                 0.0141 
                 1376.1 
                 2043.3 
                 0.0097 
               
               
                 AB001489 
                 99926_at 
                 1009.4 
                 1814.9 
                 0.0344 
                 1320.4 
                 1793.4 
                 0.0218 
               
               
                 AB010742 
                 93392_at 
                 827.0 
                 1913.7 
                 0.0034 
                 152.7 
                 232.2 
                 0.0222 
               
               
                 AF026469 
                 99064_at 
                 4105.2 
                 3382.3 
                 0.0295 
                 4249.9 
                 3171.4 
                 0.0029 
               
               
                 AI847972 
                 98521_at 
                 3108.4 
                 2425.5 
                 0.0290 
                 3010.6 
                 2311.7 
                 0.0101 
               
               
                 AI462105 
                 94963_at 
                 13498.7 
                 7326.6 
                 0.0458 
                 34083.9 
                 22131.3 
                 0.0132 
               
               
                 AW061016 
                 99964_at 
                 27.0 
                 53.5 
                 0.0144 
                 439.6 
                 40.2 
                 0.0278 
               
               
                 X69656 
                 98606_s_at 
                 1296.5 
                 733.9 
                 0.0416 
                 1631.7 
                 944.0 
                 0.0183 
               
               
                 D87661 
                 97535_at 
                 3854.3 
                 2559.2 
                 0.0014 
                 7650.0 
                 6463.3 
                 0.0086 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Gene ID 
                 Gene Title 
                 Gene Symbol 
                 PpFDRst 
               
               
                   
                   
               
               
                   
                 AE000663 
                 RIKEN cDNA 1810009J06 gene 
                 1810009J06Rik 
                 0.005 
               
               
                   
                 AA675604 
                 RIKEN cDNA 4930517K11 gene 
                 4930517K11Rik 
                 0.003 
               
               
                   
                 AI849271 
                 acetyl-Coenzyme A acyltransferase 
                 Acaa2 
                 0.004 
               
               
                   
                   
                 2 (mitochondrial 3-oxoacyl- 
               
               
                   
                   
                 Coenzyme A thiolase) 
               
               
                   
                 J04946 
                 angiotensin converting enzyme 
                 Ace 
                 0.003 
               
               
                   
                 AI838021 
                 acyl-CoA synthetase long-chain 
                 Acsl5 
                 0.003 
               
               
                   
                   
                 family member 5 
               
               
                   
                 AF045887 
                 angiotensinogen 
                 Agt 
                 0.003 
               
               
                   
                 AB027125 
                 aldo-keto reductase family 1, 
                 Akr1c12 
                 0.003 
               
               
                   
                   
                 member C12 
               
               
                   
                 M74570 
                 aldehyde dehydrogenase family 1, 
                 Aldh1a1 
                 0.003 
               
               
                   
                   
                 subfamily A1 
               
               
                   
                 AW123269 
                 anillin, actin binding protein (scraps 
                 Anln 
                 0.003 
               
               
                   
                   
                 homolog,  Drosophila ) 
               
               
                   
                 AV003419 
                 annexin A1 
                 Anxa1 
                 0.003 
               
               
                   
                 M14044 
                 annexin A2 
                 Anxa2 
                 0.005 
               
               
                   
                 AJ002390 
                 annexin A8 
                 Anxa8 
                 0.004 
               
               
                   
                 M97216 
                 amyloid beta (A4) precursor-like 
                 Aplp2 
                 0.004 
               
               
                   
                   
                 protein 2 
               
               
                   
                 X82648 
                 apolipoprotein D 
                 Apod 
                 0.008 
               
               
                   
                 D87901 
                 ADP-ribosylation factor 4 
                 Arf4 
                 0.004 
               
               
                   
                 AI852332 
                 ADP-ribosylation factor interacting 
                 Arfip2 
                 0.004 
               
               
                   
                   
                 protein 2 
               
               
                   
                 AI846773 
                 Rho GTPase activating protein 1 
                 Arhgap1 
                 0.003 
               
               
                   
                 M63725 
                 activating transcription factor 1 
                 Atf1 
                 0.033 
               
               
                   
                 U13840 
                 ATPase, H+ transporting, V0 
                 Atp6v0d1 
                 0.004 
               
               
                   
                   
                 subunit D isoform 1 
               
               
                   
                 X01838 
                 beta-2 microglobulin 
                 B2m 
                 0.003 
               
               
                   
                 X55573 
                 brain derived neurotrophic factor 
                 Bdnf 
                 0.003 
               
               
                   
                 D83745 
                 B-cell translocation gene 3 
                 Btg3 
                 0.005 
               
               
                   
                 X06454 
                 complement component 4 (within 
                 C4///Slp 
                 0.003 
               
               
                   
                   
                 H-2S)///sex-limited protein 
               
               
                   
                 M19381 
                 calmodulin 1 
                 Calm1 
                 0.005 
               
               
                   
                 M27844 
                 calmodulin 2 
                 Calm2 
                 0.004 
               
               
                   
                 AI842328 
                 calmodulin 3 
                 Calm3 
                 0.006 
               
               
                   
                 U16740 
                 capping protein (actin filament) 
                 Capza1 
                 0.007 
               
               
                   
                   
                 muscle Z-line, alpha 1 
               
               
                   
                 U16741 
                 Capping protein (actin filament) 
                 Capza2 
                 0.004 
               
               
                   
                   
                 muscle Z-line, alpha 2 
               
               
                   
                 AI747654 
                 caveolin, caveolae protein 1 
                 Cav1 
                 0.003 
               
               
                   
                 AB023418 
                 chemokine (C-C motif) ligand 8 
                 Ccl8 
                 0.003 
               
               
                   
                 X66032 
                 cyclin B2 
                 Ccnb2 
                 0.009 
               
               
                   
                 AW047630 
                 CCR4 carbon catabolite repression 
                 Ccrn4l 
                 0.025 
               
               
                   
                   
                 4-like ( S. cerevisiae ) 
               
               
                   
                 AI847784 
                 CD34 antigen 
                 Cd34 
                 0.015 
               
               
                   
                 L78075 
                 cell division cycle 42 homolog ( S.   
                 Cdc42 
                 0.003 
               
               
                   
                   
                   cerevisiae ) 
               
               
                   
                 M31131 
                 cadherin 2 
                 Cdh2 
                 0.005 
               
               
                   
                 AI854020 
                 cysteine dioxygenase 1, cytosolic 
                 Cdo1 
                 0.004 
               
               
                   
                 AV336987 
                 Centaurin, gamma 3 
                 Centg3 
                 0.008 
               
               
                   
                 AI838398 
                 capicua homolog ( Drosophila ) 
                 Cic 
                 0.005 
               
               
                   
                 Y15163 
                 Cbp/p300-interacting transactivator, 
                 Cited2 
                 0.003 
               
               
                   
                   
                 with Glu/Asp-rich carboxy-terminal 
               
               
                   
                   
                 domain, 2 
               
               
                   
                 Z18272 
                 procollagen, type VI, alpha 2 
                 Col6a2 
                 0.032 
               
               
                   
                 AF017175 
                 camitine palmitoyl transferase 1a, 
                 Cpt1a 
                 0.003 
               
               
                   
                   
                 liver 
               
               
                   
                 AV013428 
                 crystallin, alpha B 
                 Cryab 
                 0.010 
               
               
                   
                 AI837625 
                 cysteine and glycine-rich protein 1 
                 Csrp1 
                 0.003 
               
               
                   
                 U49385 
                 cytidine 5′-triphosphate synthase 2 
                 Ctps2 
                 0.003 
               
               
                   
                 U74683 
                 cathepsin C 
                 Ctsc 
                 0.003 
               
               
                   
                 AW061318 
                 CUG triplet repeat, RNA binding 
                 Cugbp2 
                 0.010 
               
               
                   
                   
                 protein 2 
               
               
                   
                 U27267 
                 chemokine (C-X-C motif) ligand 5 
                 Cxcl5 
                 0.005 
               
               
                   
                 X78445 
                 cytochrome P450, family 1, 
                 Cyp1b1 
                 0.003 
               
               
                   
                   
                 subfamily b, polypeptide 1 
               
               
                   
                 D63679 
                 decay accelerating factor 1 
                 Daf1 
                 0.016 
               
               
                   
                 AB026432 
                 damage specific DNA binding 
                 Ddb1 
                 0.005 
               
               
                   
                   
                 protein 1 
               
               
                   
                 Z38015 
                 dystrophia myotonica-protein 
                 Dmpk 
                 0.003 
               
               
                   
                   
                 kinase 
               
               
                   
                 AW060270 
                 DnaJ (Hsp40) homolog, subfamily 
                 Dnaja3 
                 0.004 
               
               
                   
                   
                 A, member 3 
               
               
                   
                 M76131 
                 eukaryotic translation elongation 
                 Eef2 
                 0.007 
               
               
                   
                   
                 factor 2 
               
               
                   
                 U57686 
                 embryonal Fyn-associated substrate 
                 Efs 
                 0.004 
               
               
                   
                 AW049716 
                 epidermal growth factor receptor 
                 Egfr 
                 0.008 
               
               
                   
                 AJ006587 
                 eukaryotic translation initiation 
                 Eif2s3x 
                 0.012 
               
               
                   
                   
                 factor 2, subunit 3, structural gene 
               
               
                   
                   
                 X-linked 
               
               
                   
                 X98471 
                 epithelial membrane protein 1 
                 Emp1 
                 0.004 
               
               
                   
                 L12703 
                 engrailed 1 
                 En1 
                 0.003 
               
               
                   
                 M29961 
                 glutamyl aminopeptidase 
                 Enpep 
                 0.003 
               
               
                   
                 J02700 
                 ectonucleotide 
                 Enpp1 
                 0.003 
               
               
                   
                   
                 pyrophosphatase/phosphodiesterase 1 
               
               
                   
                 AW122933 
                 ectonucleotide 
                 Enpp2 
                 0.004 
               
               
                   
                   
                 pyrophosphatase/phosphodiesterase 2 
               
               
                   
                 AW061222 
                 exosome component 4 
                 Exosc4 
                 0.014 
               
               
                   
                 U41739 
                 four and a half LIM domains 1 
                 Fhl1 
                 0.003 
               
               
                   
                 DI6215 
                 flavin containing monooxygenase 1 
                 Fmo1 
                 0.005 
               
               
                   
                 AF017128 
                 fos-like antigen 1 
                 Fosl1 
                 0.020 
               
               
                   
                 AI839918 
                 glycyl-tRNA synthetase 
                 Gars 
                 0.006 
               
               
                   
                 AB000096 
                 GATA binding protein 2 
                 Gata2 
                 0.012 
               
               
                   
                 L41631 
                 glucokinase 
                 Gck 
                 0.005 
               
               
                   
                 U15012 
                 growth hormone receptor 
                 Ghr 
                 0.016 
               
               
                   
                 AI153412 
                 guanine nucleotide binding protein, 
                 Gnai1 
                 0.003 
               
               
                   
                   
                 alpha inhibiting 1 
               
               
                   
                 X83577 
                 glypican 4 
                 Gpc4 
                 0.003 
               
               
                   
                 D50430 
                 glycerol phosphate dehydrogenase 
                 Gpd2 
                 0.010 
               
               
                   
                   
                 2, mitochondrial 
               
               
                   
                 AB003502 
                 G1 to S phase transition 1 
                 Gspt1 
                 0.007 
               
               
                   
                 AF043220 
                 general transcription factor II I 
                 Gtf2i 
                 0.010 
               
               
                   
                 M69069 
                 histocompatibility 2, D region locus 
                 H2-D1 
                 0.003 
               
               
                   
                   
                 1 
               
               
                   
                 X52490 
                 histocompatibility 2, D region locus 
                 H2-D1///H2-L 
                 0.003 
               
               
                   
                   
                 1///histocompatibility 2, D region 
               
               
                   
                 V00746 
                 histocompatibility 2, K1, K region 
                 H2-K1 
                 0.003 
               
               
                   
                 X16426 
                 histocompatibility 2, Q region locus 
                 H2-Q10 
                 0.003 
               
               
                   
                   
                 10 
               
               
                   
                 Y00629 
                 histocompatibility 2, T region locus 
                 H2-T23 
                 0.003 
               
               
                   
                   
                 23 
               
               
                   
                 U05837 
                 hexosaminidase A 
                 Hexa 
                 0.003 
               
               
                   
                 AF077659 
                 homeodomain interacting protein 
                 Hipk2 
                 0.007 
               
               
                   
                   
                 kinase 2 
               
               
                   
                 Y00208 
                 Homeobox A5 
                 Hoxa5 
                 0.003 
               
               
                   
                 X07439 
                 Homeobox C8 
                 Hoxc8 
                 0.003 
               
               
                   
                 X55318 
                 Homeobox C9 
                 Hoxc9 
                 0.047 
               
               
                   
                 U44389 
                 hydroxyprostaglandin 
                 Hpgd 
                 0.003 
               
               
                   
                   
                 dehydrogenase 15 (NAD) 
               
               
                   
                 AI837110 
                 heterogeneous nuclear 
                 Hrmt1l2 
                 0.007 
               
               
                   
                   
                 ribonucleoproteins 
               
               
                   
                   
                 methyltransferase-like 2 ( S.   
               
               
                   
                   
                   cerevisiae ) 
               
               
                   
                 Y15733 
                 hydroxysteroid (17-beta) 
                 Hsd17b7 
                 0.007 
               
               
                   
                   
                 dehydrogenase 7 
               
               
                   
                 AA762325 
                 inositol polyphosphate-5- 
                 Inpp5a 
                 0.003 
               
               
                   
                   
                 phosphatase A 
               
               
                   
                 M21065 
                 interferon regulatory factor 1 
                 Irf1 
                 0.005 
               
               
                   
                 Y11460 
                 integrin beta 4 binding protein 
                 Itgb4bp 
                 0.008 
               
               
                   
                 M90365 
                 junction plakoglobin 
                 Jup 
                 0.003 
               
               
                   
                 AB013345 
                 potassium channel, subfamily K, 
                 Kcnk3 
                 0.003 
               
               
                   
                   
                 member 3 
               
               
                   
                 U36340 
                 Kruppel-like factor 3 (basic) 
                 Klf3 
                 0.024 
               
               
                   
                 AW047023 
                 karyopherin (importin) alpha 3 
                 Kpna3 
                 0.016 
               
               
                   
                 AF034745 
                 ligand of numb-protein X 1 
                 Lnx1 
                 0.004 
               
               
                   
                 M63335 
                 lipoprotein lipase 
                 Lpl 
                 0.004 
               
               
                   
                 U27195 
                 leukotriene C4 synthase 
                 Ltc4s 
                 0.006 
               
               
                   
                 D86232 
                 lymphocyte antigen 6 complex, 
                 Ly6c 
                 0.003 
               
               
                   
                   
                 locus C 
               
               
                   
                 AI848045 
                 monoamine oxidase A 
                 Maoa 
                 0.003 
               
               
                   
                 AI317205 
                 mitogen activated protein kinase 
                 Map3k1 
                 0.010 
               
               
                   
                   
                 kinase kinase 1 
               
               
                   
                 Y13439 
                 mitogen-activated protein kinase 12 
                 Mapk12 
                 0.009 
               
               
                   
                 AI844810 
                 mitogen-activated protein kinase 6 
                 Mapk6 
                 0.016 
               
               
                   
                 AB005662 
                 mitogen-activated protein kinase 8 
                 Mapk8ip3 
                 0.005 
               
               
                   
                   
                 interacting protein 3 
               
               
                   
                 AF072240 
                 methyl-CpG binding domain 
                 Mbd1 
                 0.004 
               
               
                   
                   
                 protein 1 
               
               
                   
                 AI853261 
                 melanoma cell adhesion molecule 
                 Mcam 
                 0.003 
               
               
                   
                 AI841279 
                 brain acyl-CoA hydrolase 
                 MGI: 1917275 
                 0.003 
               
               
                   
                 X66402 
                 matrix metalloproteinase 3 
                 Mmp3 
                 0.003 
               
               
                   
                 J02652 
                 malic enzyme, supernatant 
                 Mod1 
                 0.018 
               
               
                   
                 AB004879 
                 muscle and microspikes RAS 
                 Mras 
                 0.004 
               
               
                   
                 AI255271 
                 major urinary protein 1///major 
                 Mup1///Mup2/// 
                 0.003 
               
               
                   
                   
                 urinary protein 2///major urinary 
                 Mup3///Mup4/// 
               
               
                   
                   
                 protein 3///major urinary protein 4/// 
                 Mup5 
               
               
                   
                   
                 major urinary protein 5 
               
               
                   
                 M16359 
                 major urinary protein 3 
                 Mup3 
                 0.003 
               
               
                   
                 X51829 
                 myeloid differentiation primary 
                 Myd116 
                 0.012 
               
               
                   
                   
                 response gene 116 
               
               
                   
                 AI648850 
                 myosin, light polypeptide 4 
                 Myl4 
                 0.008 
               
               
                   
                 AI117835 
                 myosin, light polypeptide kinase 
                 Mylk 
                 0.003 
               
               
                   
                 U96723 
                 myosin IC 
                 Myo1c 
                 0.009 
               
               
                   
                 U81453 
                 myosin VIIa 
                 Myo7a 
                 0.005 
               
               
                   
                 X61449 
                 nucleosome assembly protein 1-like 1 
                 Nap1l1 
                 0.003 
               
               
                   
                 AW125874 
                 asparaginyl-tRNA synthetase 
                 Nars 
                 0.003 
               
               
                   
                 U83148 
                 nuclear factor, interleukin 3, 
                 Nfil3 
                 0.005 
               
               
                   
                   
                 regulated 
               
               
                   
                 Y07688 
                 nuclear factor I/X 
                 Nfix 
                 0.006 
               
               
                   
                 AB017202 
                 nidogen 2 
                 Nid2 
                 0.005 
               
               
                   
                 Z49204 
                 nicotinamide nucleotide 
                 Nnt 
                 0.003 
               
               
                   
                   
                 transhydrogenase 
               
               
                   
                 AI839690 
                 NAD(P)H: quinone oxidoreductase 
                 Nqo3a2 
                 0.007 
               
               
                   
                   
                 type 3, polypeptide A2 
               
               
                   
                 X74134 
                 nuclear receptor subfamily 2, group 
                 Nr2f1 
                 0.003 
               
               
                   
                   
                 F, member 1 
               
               
                   
                 AA645293 
                 netrin 1 
                 Ntn1 
                 0.003 
               
               
                   
                 AF089751 
                 purinergic receptor P2X, ligand- 
                 P2rx4 
                 0.003 
               
               
                   
                   
                 gated ion channel 4 
               
               
                   
                 AJ009823 
                 purinergic receptor P2X, ligand- 
                 P2rx7 
                 0.009 
               
               
                   
                   
                 gated ion channel, 7 
               
               
                   
                 AI846025 
                 PAK1 interacting protein 1 
                 Pak1ip1 
                 0.009 
               
               
                   
                 AB006758 
                 protocadherin 7 
                 Pcdh7 
                 0.003 
               
               
                   
                 X57337 
                 procollagen C-proteinase enhancer 
                 Pcolce 
                 0.003 
               
               
                   
                   
                 protein 
               
               
                   
                 D50060 
                 proprotein convertase 
                 Pcsk6 
                 0.004 
               
               
                   
                   
                 subtilisin/kexin type 6 
               
               
                   
                 AA755004 
                 protein disulfide isomerase 
                 Pdia5 
                 0.003 
               
               
                   
                   
                 associated 5 
               
               
                   
                 AI842259 
                 pyruvate dehydrogenase kinase, 
                 Pdk3 
                 0.003 
               
               
                   
                   
                 isoenzyme 3 
               
               
                   
                 AF053367 
                 PDZ and LIM domain 1 (elfin) 
                 Pdlim1 
                 0.003 
               
               
                   
                 U44088 
                 pleckstrin homology-like domain, 
                 Phlda1 
                 0.003 
               
               
                   
                   
                 family A, member 1 
               
               
                   
                 AA607557 
                 phospholipase A2, group X 
                 Pla2g10 
                 0.007 
               
               
                   
                 U85711 
                 phospholipase C, delta 1 
                 Plcd1 
                 0.003 
               
               
                   
                 AW047139 
                 pleckstrin homology domain 
                 Plekhc1 
                 0.005 
               
               
                   
                   
                 containing, family C (with FERM 
               
               
                   
                   
                 domain) member 1 
               
               
                   
                 Z38110 
                 peripheral myelin protein 
                 Pmp22 
                 0.003 
               
               
                   
                 AW123013 
                 Protein phosphatase 3, regulatory 
                 Ppp3r1 
                 0.006 
               
               
                   
                   
                 subunit B, alpha isoform 
               
               
                   
                   
                 (calcineurin B, type I) 
               
               
                   
                 AF093857 
                 peroxiredoxin 6 
                 Prdx6 
                 0.045 
               
               
                   
                 AF093853 
                 peroxiredoxin 6///peroxiredoxin 6, 
                 Prdx6///Prdx6- 
                 0.006 
               
               
                   
                   
                 related sequence 1 
                 rs1 
               
               
                   
                 AW122197 
                 protein kinase, cAMP dependent 
                 Prkar1a 
                 0.004 
               
               
                   
                   
                 regulatory, type I, alpha 
               
               
                   
                 AV353694 
                 protease, serine, 25 
                 Prss25 
                 0.013 
               
               
                   
                 AW122030 
                 phosphoserine aminotransferase 1 
                 Psat1 
                 0.003 
               
               
                   
                 U22033 
                 proteosome (prosome, macropain) 
                 Psmb8 
                 0.003 
               
               
                   
                   
                 subunit, beta type 8 (large 
               
               
                   
                   
                 multifunctional protease 7) 
               
               
                   
                 D44456 
                 proteosome (prosome, macropain) 
                 Psmb9 
                 0.003 
               
               
                   
                   
                 subunit, beta type 9 (large 
               
               
                   
                   
                 multifunctional protease 2) 
               
               
                   
                 AI845915 
                 polymerase I and transcript release 
                 Ptrf 
                 0.008 
               
               
                   
                   
                 factor 
               
               
                   
                 M89777 
                 RAB3D, member RAS oncogene 
                 Rab3d 
                 0.022 
               
               
                   
                   
                 family 
               
               
                   
                 X89650 
                 RAB7, member RAS oncogene 
                 Rab7 
                 0.007 
               
               
                   
                   
                 family 
               
               
                   
                 AI844445 
                 RAB, member of RAS oncogene 
                 Rabl4 
                 0.003 
               
               
                   
                   
                 family-like 4 
               
               
                   
                 X57277 
                 RAS-related C3 botulinum substrate 1 
                 Rac1 
                 0.004 
               
               
                   
                 D64162 
                 retinoic acid early transcript 1, 
                 Raet1a///Raet1b 
                 0.007 
               
               
                   
                   
                 alpha///retinoic acid early 
                 ///Raet1c/// 
               
               
                   
                   
                 transcript beta///retinoic acid early 
                 Raet1d///Raet1e 
               
               
                   
                   
                 transcript gamma///retinoic acid 
               
               
                   
                   
                 early transcript delta///retinoic acid 
               
               
                   
                   
                 early transcript 1E 
               
               
                   
                 AI847564 
                 RAN binding protein 5 
                 Ranbp5 
                 0.007 
               
               
                   
                 AB016424 
                 RNA binding motif protein 3 
                 Rbm3 
                 0.004 
               
               
                   
                 AW046449 
                 RNA binding motif, single stranded 
                 Rbms1 
                 0.005 
               
               
                   
                   
                 interacting protein 1 
               
               
                   
                 AI048434 
                 RER1 retention in endoplasmic 
                 Rer1 
                 0.013 
               
               
                   
                   
                 reticulum 1 homolog ( S. cerevisiae ) 
               
               
                   
                 AF014371 
                 ras homolog gene family, member A 
                 Rhoa 
                 0.006 
               
               
                   
                 AW121012 
                 ring finger protein (C3HC4 type) 19 
                 Rnf19 
                 0.006 
               
               
                   
                 U58513 
                 Rho-associated coiled-coil forming 
                 Rock2 
                 0.003 
               
               
                   
                   
                 kinase 2 
               
               
                   
                 M83218 
                 S100 calcium binding protein A8 
                 S100a8 
                 0.007 
               
               
                   
                   
                 (calgranulin A) 
               
               
                   
                 X03505 
                 serum amyloid A 3 
                 Saa3 
                 0.008 
               
               
                   
                 L10244 
                 spermidine/spermine N1-acetyl 
                 Sat1 
                 0.008 
               
               
                   
                   
                 transferase 1 
               
               
                   
                 AB008553 
                 scavenger receptor class B, member 
                 Scarb2 
                 0.012 
               
               
                   
                   
                 2 
               
               
                   
                 M21285 
                 stearoyl-Coenzyme A desaturase 1 
                 Scd1 
                 0.006 
               
               
                   
                 U88567 
                 secreted frizzled-related sequence 
                 Sfrp2 
                 0.003 
               
               
                   
                   
                 protein 2 
               
               
                   
                 U66918 
                 short stature Homeobox 2 
                 Shox2 
                 0.003 
               
               
                   
                 AJ243651 
                 solute carrier family 39 (zinc 
                 Slc39a1 
                 0.023 
               
               
                   
                   
                 transporter), member 1 
               
               
                   
                 AF004666 
                 solute carrier family 8 
                 Slc8a1 
                 0.003 
               
               
                   
                   
                 (sodium/calcium exchanger), 
               
               
                   
                   
                 member 1 
               
               
                   
                 AI839882 
                 small fragment nuclease 
                 Smfn 
                 0.003 
               
               
                   
                 U88328 
                 suppressor of cytokine signaling 3 
                 Socs3 
                 0.003 
               
               
                   
                 AJ005567 
                 small proline-rich protein 2I 
                 Sprr2i 
                 0.006 
               
               
                   
                 AI837107 
                 single-stranded DNA binding 
                 Ssbp2 
                 0.005 
               
               
                   
                   
                 protein 2 
               
               
                   
                 U47323 
                 stromal interaction molecule 1 
                 Stim1 
                 0.008 
               
               
                   
                 AI842665 
                 Tax1 (human T-cell leukemia virus 
                 Tax1bp3 
                 0.008 
               
               
                   
                   
                 type I) binding protein 3 
               
               
                   
                 AF041822 
                 T-box 15 
                 Tbx15 
                 0.003 
               
               
                   
                 U86137 
                 telomerase associated protein 1 
                 Tep1 
                 0.003 
               
               
                   
                 L19932 
                 transforming growth factor, beta 
                 Tgfbi 
                 0.013 
               
               
                   
                   
                 induced 
               
               
                   
                 X14432 
                 thrombomodulin 
                 Thbd 
                 0.003 
               
               
                   
                 M62470 
                 thrombospondin 1 
                 Thbs1 
                 0.004 
               
               
                   
                 AI849587 
                 transmembrane protein 37 
                 Tmem37 
                 0.017 
               
               
                   
                 AI852433 
                 transportin 2 (importin 3, 
                 Tnpo2 
                 0.008 
               
               
                   
                   
                 karyopherin beta 2b) 
               
               
                   
                 L31777 
                 triosephosphate isomerase 1 
                 Tpi1 
                 0.003 
               
               
                   
                 M28729 
                 tubulin, alpha 1 
                 Tuba1 
                 0.004 
               
               
                   
                 M13441 
                 tubulin, alpha 6 
                 Tuba6 
                 0.003 
               
               
                   
                 M28739 
                 tubulin, beta 2 
                 Tubb2 
                 0.003 
               
               
                   
                 X04663 
                 tubulin, beta 5 
                 Tubb5 
                 0.003 
               
               
                   
                 AI840882 
                 thioredoxin-like 2 
                 Txnl2 
                 0.012 
               
               
                   
                 AW046479 
                 ubiquitin-activating enzyme E1-like 
                 Ube1l 
                 0.005 
               
               
                   
                 AB001489 
                 upstream binding transcription 
                 Ubtf 
                 0.008 
               
               
                   
                   
                 factor, RNA polymerase I 
               
               
                   
                 AB010742 
                 uncoupling protein 3 
                 Ucp3 
                 0.003 
               
               
                   
                   
                 (mitochondrial, proton carrier) 
               
               
                   
                 AF026469 
                 ubiquitin specific protease 4 (proto- 
                 Usp4 
                 0.005 
               
               
                   
                   
                 oncogene) 
               
               
                   
                 AI847972 
                 vesicle-associated membrane 
                 Vamp3 
                 0.005 
               
               
                   
                   
                 protein 3 
               
               
                   
                 AI462105 
                 vinculin 
                 Vcl 
                 0.007 
               
               
                   
                 AW061016 
                 vitamin D receptor 
                 Vdr 
                 0.004 
               
               
                   
                 X69656 
                 tryptophanyl-tRNA synthetase 
                 Wars 
                 0.005 
               
               
                   
                 D87661 
                 tyrosine 3- 
                 Ywhah/// 
                 0.003 
               
               
                   
                   
                 monooxygenase/tryptophan 5- 
                 LOC545556 
               
               
                   
                   
                 monooxygenase activation protein, 
               
               
                   
                   
                 eta polypeptide///similar to 14-3-3 
               
               
                   
                   
                 protein eta 
               
               
                   
                   
               
               
                   
                 Epididymal isolated adipocytes: Ae; subcutaneous isolated adipocytes: Asc; epidydimal stromovascular fraction: Se; subcutaneous stromovascular fraction: Ssc 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Genes Involved in Embryonic Development, Pattern Specification, Mesoderm Formation and Organogenesis (198 Genes). 
               
            
           
           
               
               
               
               
            
               
                 Public ID 
                 Gene Title 
                 Gene Symbol 
                 Probesets 
               
               
                   
               
               
                 L15436 
                 Activin A receptor, type 1 
                 Acvr1 
                 93460_at 
               
               
                 Z31663 
                 Activin A receptor, type 1B 
                 Acvr1b 
                 101177_at 
               
               
                 M84120 
                 Activin receptor IIB 
                 Acvr2b 
                 93903_at 
               
               
                 X99273 
                 Aldehyde dehydrogenase family 1, subfamily A2 
                 Aldh1a2 
                 101707_at 
               
               
                 AI854771 
                 Angiomotin 
                 Amot 
                 95531_at 
               
               
                 M88127 
                 Adenomatosis polyposis  coli   
                 Apc 
                 101447_at 
               
               
                 M37890 
                 Androgen receptor 
                 Ar 
                 92667_at 
               
               
                 U77628 
                 Achaete-scute complex homolog-like 2 ( Drosophila ) 
                 Ascl2 
                 101355_at 
               
               
                 AB013819 
                 Baculoviral IAP repeat-containing 5 
                 Birc5 
                 101521_at 
               
               
                 AA518586 
                 Bone morphogenetic protein 1 
                 Bmp1 
                 92701_at, 95557_at 
               
               
                 L25602 
                 Bone morphogenetic protein 2 
                 Bmp2 
                 102559_at, 161118_r_at 
               
               
                 X56848 
                 Bone morphogenetic protein 4 
                 Bmp4 
                 93455_s_at, 93456_r_at 
               
               
                 L41145 
                 Bone morphogenetic protein 5 
                 Bmp5 
                 99393_at 
               
               
                 X56906 
                 Bone morphogenetic protein 7 
                 Bmp7 
                 93243_at 
               
               
                 D16250 
                 Bone morphogenetic protein receptor, type 1A 
                 Bmpr1a 
                 92767_at 
               
               
                 Z23143 
                 Bone morphogenetic protein receptor, type 1B 
                 Bmpr1b 
                 97725_at 
               
               
                 AF003942 
                 Bone morphogenic protein receptor, type II (serine/threonine 
                 Bmpr2 
                 99865_at 
               
               
                 AF012104 
                 BMX non-receptor tyrosine kinase 
                 Bmx 
                 98840_at 
               
               
                 M64292 
                 B-cell translocation gene 2, anti-proliferative 
                 Btg2 
                 101583_at 
               
               
                 M80463 
                 Caudal type Homeobox 1 
                 Cdx1 
                 103477_at 
               
               
                 U00454 
                 Caudal type Homeobox 2 
                 Cdx2 
                 103239_at 
               
               
                 AI851751 
                 Chromodomain helicase DNA binding protein 8 
                 Chd8 
                 104059_at, 99821_at 
               
               
                 AF069501 
                 Chordin 
                 Chrd 
                 103249_at 
               
               
                 AF071313 
                 COP9 (constitutive photomorphogenic) homolog, subunit 3 
                 Cops3 
                 99113_at 
               
               
                 M90364 
                 Catenin (cadherin associated protein), beta 1, 88 kda 
                 Ctnnb1 
                 160430_at 
               
               
                 AI851990 
                 Catenin beta interacting protein 1 
                 Ctnnbip1 
                 99492_at 
               
               
                 AW123921 
                 Disabled homolog 2 ( Drosophila ) 
                 Dab2 
                 104633_at, 98044_at, 98045_s_at 
               
               
                 AV238668 
                 Desert hedgehog 
                 Dhh 
                 161111_f_at, 161588_r_at, 
               
               
                 X86925 
                 E2F transcription factor 5 
                 E2f5 
                 98995_at 
               
               
                 X76858 
                 E4F transcription factor 1 
                 E4f1 
                 104689_at 
               
               
                 U35233 
                 Endothelin 1 
                 Edn1 
                 102737_at, 102738_s_at 
               
               
                 U07602 
                 Ephrin B1 
                 Efnb1 
                 98407_at 
               
               
                 U30244 
                 Ephrin B2 
                 Efnb2 
                 160857_at 
               
               
                 AF016294 
                 E74-like factor 3 
                 Elf3 
                 99059_at 
               
               
                 L12703 
                 Engrailed 1 
                 En1 
                 96523_at 
               
               
                 Y00203 
                 Engrailed 2 
                 En2 
                 98338_at 
               
               
                 L25890 
                 Eph receptor B2 
                 Ephb2 
                 98771_at 
               
               
                 X96639 
                 Exostoses (multiple) 1 
                 Ext1 
                 102811_at 
               
               
                 U61110 
                 Eyes absent 1 homolog ( Drosophila ) 
                 Eya1 
                 94705_at, 94706_s_at 
               
               
                 D89080 
                 Fibroblast growth factor 10 
                 Fgf10 
                 95976_at 
               
               
                 D12483 
                 Fibroblast growth factor 8 
                 Fgf8 
                 97742_s_at 
               
               
                 AF030635 
                 FK506 binding protein 8 
                 Fkbp8 
                 100613_at 
               
               
                 L35949 
                 Forkhead box f1a 
                 Foxf1a 
                 93704_at 
               
               
                 U36760 
                 Forkhead box G1 
                 Foxg1 
                 161049_at 
               
               
                 AF069303 
                 Forkhead box H1 
                 Foxh1 
                 97789_at 
               
               
                 L13204 
                 Forkhead box J1 
                 Foxj1 
                 98831_at 
               
               
                 X92498 
                 Forkhead box L1 
                 Foxl1 
                 101185_at 
               
               
                 U68058 
                 Frizzled-related protein 
                 Frzb 
                 104672_at 
               
               
                 Z29532 
                 Follistatin 
                 Fst 
                 98817_at 
               
               
                 AF054623 
                 Frizzled homolog 1 ( Drosophila ) 
                 Fzd1 
                 161040_at 
               
               
                 AW123618 
                 Frizzled homolog 2 ( Drosophila ) 
                 Fzd2 
                 93681_at 
               
               
                 AU020229 
                 Frizzled homolog 3 ( Drosophila ) 
                 Fzd3 
                 98169_s_at, 98348_at 
               
               
                 AW122897 
                 Frizzled homolog 4 ( Drosophila ) 
                 Fzd4 
                 93459_s_at, 95771_i_at, 
               
               
                 U43319 
                 Frizzled homolog 6 ( Drosophila ) 
                 Fzd6 
                 101142_at 
               
               
                 U43320 
                 Frizzled homolog 7 ( Drosophila ) 
                 Fzd7 
                 101143_at 
               
               
                 U43321 
                 Frizzled homolog 8 ( Drosophila ) 
                 Fzd8 
                 99415_at 
               
               
                 Y17709 
                 Frizzled homolog 9 ( Drosophila ) 
                 Fzd9 
                 99844_at 
               
               
                 D88611 
                 Glial cells missing homolog 2 ( Drosophila ) 
                 Gcm2 
                 94709_at, 94710_g_at 
               
               
                 AF100906 
                 Growth differentiation factor 11 
                 Gdf11 
                 101814_at 
               
               
                 M63801 
                 Gap junction membrane channel protein alpha 1 
                 Gja1 
                 100064_f_at, 100065_r_at 
               
               
                 X61675 
                 Gap junction membrane channel protein alpha 5 
                 Gja5 
                 101778_at 
               
               
                 X95255 
                 GLI-Kruppel family member GLI3 
                 Gli3 
                 101182_at 
               
               
                 AA681520 
                 Geminin 
                 Gmnn 
                 160069_at 
               
               
                 AI843313 
                 Glypican 3 
                 Gpc3 
                 160158_at 
               
               
                 X83577 
                 Glypican 4 
                 Gpc4 
                 102886_at 
               
               
                 AF045801 
                 Gremlin 1 
                 Grem1 
                 101758_at 
               
               
                 AB017132 
                 Hematopoietically expressed Homeobox 
                 Hhex 
                 98408_at 
               
               
                 M62766 
                 3-hydroxy-3-methylglutaryl-Coenzyme A reductase 
                 Hmgcr 
                 104285_at, 99425_at 
               
               
                 M22115 
                 Homeobox A1 
                 Hoxa1 
                 95297_at 
               
               
                 L08757 
                 Homeobox A10 
                 Hoxa10 
                 92970_at 
               
               
                 U20371 
                 Homeobox A11 
                 Hoxa11 
                 104021_at 
               
               
                 U59322 
                 Homeobox A13 
                 Hoxa13 
                 94636_at 
               
               
                 M93148 
                 Homeobox A2 
                 Hoxa2 
                 102643_at 
               
               
                 Y11717 
                 Homeobox A3 
                 Hoxa3 
                 102087_at 
               
               
                 AV279579 
                 Homeobox A4 
                 Hoxa4 
                 162402_r_at 
               
               
                 Y00208 
                 Homeobox A5 
                 Hoxa5 
                 103086_at, 97745_at, 97746_f_at 
               
               
                 M11988 
                 Homeobox A6 
                 Hoxa6 
                 102579_f_at 
               
               
                 M17192 
                 Homeobox A7 
                 Hoxa7 
                 102864_at, 102580_r_at 
               
               
                 AB005458 
                 Homeobox A9 
                 Hoxa9 
                 92745_at 
               
               
                 X53063 
                 Homeobox B1 
                 Hoxb1 
                 93888_at 
               
               
                 U57051 
                 Homeobox B13 
                 Hoxb13 
                 99808_at 
               
               
                 U02278 
                 Homeobox B3 
                 Hoxb3 
                 98780_at 
               
               
                 M36654 
                 Homeobox B4 
                 Hoxb4 
                 92255_at 
               
               
                 M26283 
                 Homeobox B5 
                 Hoxb5 
                 103666_at 
               
               
                 M18401 
                 Homeobox B6 
                 Hoxb6 
                 103445_at 
               
               
                 M18400 
                 Homeobox B7 
                 Hoxb7 
                 92914_at 
               
               
                 M18399 
                 Homeobox B8 
                 Hoxb8 
                 96417_s_at 
               
               
                 M34857 
                 Homeobox B9 
                 Hoxb9 
                 103952_at 
               
               
                 X69019 
                 Homeobox C4 
                 Hoxc4 
                 102660_at 
               
               
                 U28071 
                 Homeobox C5 
                 Hoxc5 
                 95312_at 
               
               
                 M35986 
                 Homeobox C6 
                 Hoxc6 
                 99980_at 
               
               
                 X07439 
                 Homeobox C8 
                 Hoxc8 
                 93378_at 
               
               
                 X55318 
                 Homeobox C9 
                 Hoxc9 
                 92891_f_at 
               
               
                 M87802 
                 Homeobox D1 
                 Hoxd1 
                 98819_at 
               
               
                 X62669 
                 Homeobox D10 
                 Hoxd10 
                 103741_at, 98820_g_at 
               
               
                 X58849 
                 Homeobox D12 
                 Hoxd12 
                 99427_at 
               
               
                 X99291 
                 Homeobox D13 
                 Hoxd13 
                 102567_at 
               
               
                 X73572 
                 Homeobox D3 
                 Hoxd3 
                 98367_at 
               
               
                 U77364 
                 Homeobox D4 
                 Hoxd4 
                 102380_s_at 
               
               
                 AI837887 
                 Homeobox D8 
                 Hoxd8 
                 160460_at 
               
               
                 X62669 
                 Homeobox D9 
                 Hoxd9 
                 99426_at, 93221_at 
               
               
                 AI837110 
                 Heterogeneous nuclear ribonucleoproteins methyltransferase-like 2 
                 Hrmt1l2 
                 96696_at 
               
               
                 X04480 
                 Insulin-like growth factor 1 
                 Igf1 
                 95545_at 
               
               
                 X71922 
                 Insulin-like growth factor 2 
                 Igf2 
                 98622_at, 95546_g_at 
               
               
                 X76291 
                 Indian hedgehog 
                 Ihh 
                 103949_at, 98623_g_at 
               
               
                 J05149 
                 Insulin receptor 
                 Insr 
                 102146_at 
               
               
                 D12645 
                 Kinesin family member 3A 
                 Kif3a 
                 100398_at, 161275_at 
               
               
                 M36775 
                 Laminin, alpha 1 
                 Lama1 
                 103729_at 
               
               
                 U12147 
                 Laminin, alpha 2 
                 Lama2 
                 92366_at 
               
               
                 X84014 
                 Laminin, alpha 3 
                 Lama3 
                 97790_s_at, 
               
               
                 U69176 
                 Laminin, alpha 4 
                 Lama4 
                 104587_at 
               
               
                 AV236263 
                 Laminin, alpha 5 
                 Lama5 
                 161702_f_at 
               
               
                 AA874589 
                 LIM and senescent cell antigen-like domains 1 
                 Lims1 
                 104634_at, 161793_at 
               
               
                 AF064984 
                 Low density lipoprotein receptor-related protein 5 
                 Lrp5 
                 103806_at, 99931_at 
               
               
                 AF074265 
                 Low density lipoprotein receptor-related protein 6 
                 Lrp6 
                 103271_at 
               
               
                 AV317327 
                 Mitogen activated protein kinase 1 
                 Mapk1 
                 161583_at 
               
               
                 Z14249 
                 Mitogen activated protein kinase 3 
                 Mapk3 
                 101834_at 
               
               
                 AW120605 
                 Myeloid/lymphoid or mixed lineage-leukemia translocation to 3 
                 Mllt3 
                 103925_at, 93253_at, 93254_at 
               
               
                 AA414339 
                 Nuclear receptor coactivator 6 
                 Ncoa6 
                 95351_at 
               
               
                 AF074926 
                 N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 1 
                 Ndst1 
                 92516_at 
               
               
                 AF091351 
                 NK2 transcription factor related, locus 5 ( Drosophila ) 
                 Nkx2-5 
                 97777_at, 95525_at 
               
               
                 U79163 
                 Noggin 
                 Nog 
                 97727_at, 93590_at 
               
               
                 X74134 
                 Nuclear receptor subfamily 2, group F, member 1 
                 Nr2f1 
                 102715_at 
               
               
                 X76653 
                 Nuclear receptor subfamily 2, group F, member 2 
                 Nr2f2 
                 103052_r_at 
               
               
                 AF010130 
                 Neuregulin 3 
                 Nrg3 
                 99834_at 
               
               
                 M20978 
                 Paired box gene 1 
                 Pax1 
                 96595_at, 161792_f_at 
               
               
                 X55781 
                 Paired box gene 2 
                 Pax2 
                 99809_at 
               
               
                 X59358 
                 Paired box gene 3 
                 Pax3 
                 100697_at 
               
               
                 AB010557 
                 Paired box gene 4 
                 Pax4 
                 99908_at 
               
               
                 M97013 
                 Paired box gene 5 
                 Pax5 
                 102578_at 
               
               
                 X63963 
                 Paired box gene 6 
                 Pax6 
                 92271_at 
               
               
                 X57487 
                 Paired box gene 8 
                 Pax8 
                 96504_at, 96993_at 
               
               
                 X84000 
                 Paired box gene 9 
                 Pax9 
                 98838_at 
               
               
                 M29464 
                 Platelet derived growth factor, alpha 
                 Pdgfa 
                 94932_at 
               
               
                 AI840738 
                 Platelet derived growth factor receptor, alpha polypeptide 
                 Pdgfra 
                 160332_at 
               
               
                 Y15443 
                 Pleckstrin homology-like domain, family A, member 2 
                 Phlda2 
                 104548_at 
               
               
                 AI747899 
                 Phosphatidylinositol transfer protein, beta 
                 Pitpnb 
                 102696_s_at, 161202_r_at, 
               
               
                 U70132 
                 Paired-like homeodomain transcription factor 2 
                 Pitx2 
                 102788_s_at 
               
               
                 AF027185 
                 Phospholipase C, gamma 1 
                 Plcg1 
                 98290_at, 102697_at, 104557_at 
               
               
                 AF000294 
                 Peroxisome proliferator activated receptor binding protein 
                 Pparbp 
                 160603_at, 161340_r_at 
               
               
                 Z67745 
                 Protein phosphatase 2a, catalytic subunit, alpha isoform 
                 Ppp2ca 
                 92638_at 
               
               
                 U77946 
                 Paired like homeodomain factor 1 
                 Prop1 
                 100698_at 
               
               
                 AI848841 
                 Patched homolog 1 
                 Ptch1 
                 104030_at 
               
               
                 Z22821 
                 RAB23, member RAS oncogene family 
                 Rab23 
                 93718_at 
               
               
                 AV375524 
                 V-rel reticuloendotheliosis viral oncogene homolog A (avian) 
                 Rela 
                 162042_i_at, 104031_at 
               
               
                 U88566 
                 Secreted frizzled-related sequence protein 1 
                 Sfrp1 
                 97997_at 
               
               
                 U88567 
                 Secreted frizzled-related sequence protein 2 
                 Sfrp2 
                 93503_at, 97813_at 
               
               
                 AF117709 
                 Secreted frizzled-related sequence protein 4 
                 Sfrp4 
                 92469_at 
               
               
                 X76290 
                 Sonic hedgehog 
                 Shh 
                 101831_at 
               
               
                 U66918 
                 Short stature Homeobox 2 
                 Shox2 
                 99042_s_at 
               
               
                 AI641895 
                 Shroom 
                 Shrm 
                 100024_at 
               
               
                 U40576 
                 Single-minded homolog 2 
                 Sim2 
                 92896_s_at 
               
               
                 U17132 
                 Solute carrier family 30 (zinc transporter), member 1 
                 Slc30a1 
                 93938_at, 99043_s_at 
               
               
                 U58992 
                 MAD homolog 1 ( Drosophila ) 
                 Smad1 
                 102983_at 
               
               
                 U60530 
                 MAD homolog 2 ( Drosophila ) 
                 Smad2 
                 104536_at 
               
               
                 AB008192 
                 MAD homolog 3 ( Drosophila ) 
                 Smad3 
                 93613_at, 102984_g_at 
               
               
                 U79748 
                 MAD homolog 4 ( Drosophila ) 
                 Smad4 
                 160440_at 
               
               
                 U58993 
                 MAD homolog 5 ( Drosophila ) 
                 Smad5 
                 102865_at 
               
               
                 U85614 
                 SWI/SNF related, matrix associated, actin dependent regulator of 
                 Smarcc1 
                 102062_at 
               
               
                 AF089721 
                 Smoothened homolog ( Drosophila ) 
                 Smo 
                 96812_at 
               
               
                 AA866668 
                 SRY-box containing gene 3 
                 Sox3 
                 103301_i_at 
               
               
                 X51683 
                 Brachyury 
                 T 
                 93941_at, 92264_at 
               
               
                 AF013282 
                 T-box 15 
                 Tbx15 
                 100354_at, 103302_r_at 
               
               
                 AA755817 
                 T-box 2 
                 Tbx2 
                 104655_at, 102256_at 
               
               
                 AW121328 
                 T-box 3 
                 Tbx3 
                 103538_at, 100355_g_at 
               
               
                 U57331 
                 T-box 6 
                 Tbx6 
                 93611_at, 92705_at 
               
               
                 AB008174 
                 Transcription factor 2 
                 Tcf2 
                 101396_at 
               
               
                 AF035717 
                 Transcription factor 21 
                 Tcf21 
                 103050_at 
               
               
                 AI841235 
                 Transcription factor 3 
                 Tcf3 
                 104458_at, 162159_i_at 
               
               
                 AJ009862 
                 Transforming growth factor, beta 1 
                 Tgfb1 
                 101918_at 
               
               
                 M32745 
                 Transforming growth factor, beta 3 
                 Tgfb3 
                 102751_at, 160780_at 
               
               
                 D25540 
                 Transforming growth factor, beta receptor I 
                 Tgfbr1 
                 92427_at 
               
               
                 X14432 
                 Thrombomodulin 
                 Thbd 
                 104601_at, 161382_at 
               
               
                 AF019048 
                 Tumor necrosis factor (ligand) superfamily, member 11 
                 Tnfsf11 
                 93416_at 
               
               
                 AI122079 
                 Tnf receptor-associated factor 6 
                 Traf6 
                 104189_at, 162023_f_at 
               
               
                 AB010152 
                 Transformation related protein 63 
                 Trp63 
                 103810_at, 98874_at 
               
               
                 L31959 
                 Tetratricopeptide repeat domain 10 
                 Ttc10 
                 100404_at, 104190_at 
               
               
                 AW060819 
                 Twisted gastrulation homolog 1 ( Drosophila ) 
                 Twsg1 
                 102032_at 
               
               
                 AF089812 
                 Ubiquitin-conjugating enzyme E2A, RAD6 homolog ( S. Cerevisiae ) 
                 Ube2a 
                 96695_at, 162392_r_at 
               
               
                 AW061016 
                 Vitamin D receptor 
                 Vdr 
                 99964_at 
               
               
                 M95200 
                 Vascular endothelial growth factor A 
                 Vegfa 
                 103520_at, 99965_at 
               
               
                 U73620 
                 Vascular endothelial growth factor C 
                 Vegfc 
                 94712_at 
               
               
                 M11943 
                 Wingless-related MMTV integration site 1 
                 Wnt1 
                 94134_at 
               
               
                 U61969 
                 Wingless related MMTV integration site 10a 
                 Wnt10a 
                 98862_at 
               
               
                 AF029307 
                 Wingless related MMTV integration site 10b 
                 Wnt10b 
                 92750_s_at, 92752_r_at 
               
               
                 X70800 
                 Wingless-related MMTV integration site 11 
                 Wnt11 
                 103490_at, 92751_i_at 
               
               
                 AF070988 
                 Wingless related MMTV integration site 2b 
                 Wnt2b 
                 94126_at 
               
               
                 M32502 
                 Wingless-related MMTV integration site 3 
                 Wnt3 
                 99325_at 
               
               
                 X56842 
                 Wingless-related MMTV integration site 3A 
                 Wnt3a 
                 102667_at 
               
               
                 M89797 
                 Wingless-related MMTV integration site 4 
                 Wnt4 
                 103238_at 
               
               
                 M89798 
                 Wingless-related MMTV integration site 5A 
                 Wnt5a 
                 99390_at 
               
               
                 M89799 
                 Wingless-related MMTV integration site 5B 
                 Wnt5b 
                 103513_at 
               
               
                 M89800 
                 Wingless-related MMTV integration site 6 
                 Wnt6 
                 103735_at 
               
               
                 M89801 
                 Wingless-related MMTV integration site 7A 
                 Wnt7a 
                 101316_at 
               
               
                 M89802 
                 Wingless-related MMTV integration site 7B 
                 Wnt7b 
                 92404_at 
               
               
                 Z68889 
                 Wingless-related MMTV integration site 8A 
                 Wnt8a 
                 99361_at 
               
               
                 AI553024 
                 Zinc finger and BTB domain containing 16 
                 Zbtb16 
                 92201_at 
               
               
                 D70849 
                 Zinc finger protein of the cerebellum 3 
                 Zic3 
                 98330_at 
               
               
                   
               
            
           
         
       
     
     Example 2 
     Confirmation of Interdepot Gene Expression Differences by Real Time PCR (RT-PCR) 
     The differences of expression in genes involved in embryonic development and pattern specification described in Example 1 were confirmed by quantitative RT-PCR. 
     Analysis of Gene Expression by Real Time PCR 
     Expression of murine and human genes of particular interest based on the microarray analysis (Tbx15, Shox2, En1, Sfrp2, HoxC9, Nr2f1, Apc4, Thbd, HoxA5 and HoxC8) was further assesses by quantitative real-time RT-PCR. For murine samples, 1 μg of total RNA was reverse transcribed in 20 μl using Advantage RT-for-PCR kit (BD Biosciences, Palo Alto, USA) according manufacturer&#39;s instructions. 5 μl of diluted (1/20) reverse transcription reaction was amplified with specific primers (300 nM each) in a 20 μl PCR using a SYBR Green PCR Master Mix (Applied Biosystems, Forest City, USA). For human samples, total RNA was isolated from paired subcutaneous and visceral adipose tissue samples using TRIzol (Life Technologies, Inc., Grand Island, N.Y.), and 1 μg RNA was reverse transcribed with standard reagents (Life Technologies, Inc., Grand Island, N.Y.). 2 μl of each RT reaction was amplified in a 26 μl PCR using the Brilliant SYBR Green QPCR Core Reagent Kit from Stratagene (La Jolla, Calif.). Analysis of murine and human gene expression were assessed in the ABI PRISM 7000 sequence detector for an initial denaturation at 95° C. for 10 minutes, followed by 40 PCR cycles, each cycle consisting of 95° C. for 15 seconds, 60° C. for 1 minute, and 72° C. for 1 minute and SYBR Green fluorescence emissions were monitored after each cycle. For each gene, mRNA expression was calculated relative to 36B4 for human samples and TBP for murine samples. Amplification of specific transcripts was confirmed by melting curve profiles (cooling the sample to 68° C. and heating slowly to 95° C. with measurement of fluorescence) at the end of each PCR. The specificity of the PCR was further verified by subjecting the amplification products to agarose gel electrophoresis. Primer sequences for each gene are given in Table 3. 
     In whole tissue, all predominantly subcutaneous genes Tbx15, Shox2, En1, Sfrp2 and HoxC9 were more highly expressed in subcutaneous adipose tissue as compared to intra-abdominal (epididymal) fat, with the most marked differences observed for Tbx15, Shox2, and En1 expression (39-, 23-, and 5.4-fold respectively; p=0.005, 0.018, and 0.008, respectively) ( FIG. 2A ). Conversely, all predominant intra-abdominal genes Nr2f1, Gpc4, Thbd, HoxA5 and HoxC8 were significantly more expressed in intra-abdominal adipose tissue as compared to subcutaneous adipose tissue by 2.1- to 3.5-fold (all p&lt;0.05) ( FIG. 3A ). 
     Likewise, differences were confirmed in isolated adipocytes and stromovascular cells obtained from both depots by qPCR. Thus, both adipocytes and SVF cells isolated from subcutaneous adipose tissue expressed higher level of all subcutaneous genes Tbx15 [140- and 460-fold (p=0.001 and 0.013)], Shox2 [20- and 205-fold (p=0.006 and 0.012)], En1; [12.3- and 4.9-fold (p=0.0006 and 0.0007)], Sfrp2 [2.6- and 4.5-fold (p=0.001 and 0.04)] and HoxC9 [1.8- and 2.1-fold (p=0.023 and 0.06)] ( FIG. 2B ). Conversely, adipocytes and SVF from epididymal adipose tissue expressed higher level of intra-abdominal genes Nr2f1, Gpc4, Thbd, HoxA5 and HoxC8 [5.4- and 7.8-fold (p=0.006 and 0.003); 2.1- and 1.5-fold (p=0.003 and 0.05); 3.8- and 0.7-fold (p=0.004 and 0.3); 1.6- and 2.2-fold (p=0.04 and 0.02); 3.8- and 1.7-fold (p=0.009 and 0.02), respectively] ( FIG. 3B ). 
     
       
         
           
               
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Primers list for real time PCR 
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Accession 
                   
                 SEQ ID 
                   
                 SEQ ID 
                   
               
               
                 Name 
                 number 
                 Forward primer (5′-3′) 
                 NO: 
                 Reverse primer (5′-3′) 
                 NO: 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 T-box 15 
                 Human: 
                 CGAGTTCATGTGATTCGCAAAG 
                 1 
                 TAGGCCGTAACT 
                 2 
                   
               
               
                 (Tbx15) 
                 NM_152380 
                   
                   
                 GTGGTGAACA 
               
               
                   
                 Murine: 
                 TGTTCGCACACTGACCTTTG 
                 3 
                 CCAGTGCTGGAG 
                 4 
               
               
                   
                 NM_009323 
                   
                   
                 GTGGTT 
               
               
                   
               
               
                 Short stature 
                 Human: 
                 CCGCCAGCCAGTTTGAAG 
                 5 
                 GCGCTGTGGCGC 
                 6 
               
               
                 Homeobox 2 
                 NM_006884 
                   
                   
                 ACGCGC 
               
               
                 (Shox2) 
                 Murine: 
                 TGGAACAACTCAA 
                 7 
                 TTCAAACTGGCT 
                 8 
               
               
                   
                 NM_013665 
                 CGAGCTGGAGA 
                   
                 AGCGGCTCCTAT 
               
               
                   
               
               
                 Engrailed 1 
                 Human: 
                 TTCGGATCGTCCATCCTCC 
                 9 
                 GCTCCGTGATGT 
                 10 
               
               
                 (En1) 
                 NM_001426 
                   
                   
                 AGCGGTTT 
               
               
                   
                 Murine: 
                 ACACAACCCTGCGATCCTACTC 
                 11 
                 CGCTTGTCTTCCTT 
                 12 
               
               
                   
                 NM_010133 
                   
                   
                 CTCGTTCT 
               
               
                   
               
               
                 Secreted 
                 Human: 
                 CCGAAAGGGACCTGAAGAAATC 
                 13 
                 GCTCCCCA 
                 14 
               
               
                 frizzled- 
                 NM_003013 
                   
                   
                 CCCTGTTTCTG 
                   
               
               
                 related protein 
                 Murine: 
                 AGGACAACGACCTCTGCATC 
                 15 
                 TGTCGTCCTC 
                 16 
               
               
                 2 (Sfrp2) 
                 NM_009144 
                   
                   
                 ATTCTTGGTTT 
               
               
                   
               
               
                 Homeobox C9 
                 Human: 
                 CAGCAACCCCGTGGCC 
                 17 
                 CCGACGGTCC 
                 18 
               
               
                 (HoxC9) 
                 NM_006897 
                   
                   
                 CTGGTTAAA 
               
               
                   
                 Murine: 
                 CAGCAAGCACAAAGAGGAGA 
                 19 
                 CGACGGTCCCTG 
                 20 
               
               
                   
                 NM_008272 
                   
                   
                 GTTAAATAC 
               
               
                   
               
               
                 Nuclear 
                 Human: 
                 TCAAAGCCATCGTGCTGTTC 
                 21 
                 AGTGCGCACTGG 
                 22 
               
               
                 receptor 
                 NM_005654 
                   
                   
                 AGGAGTACG 
               
               
                 subfamily 2, 
                 Murine: 
                 ACATCCGCATCTTTCAGGAAC 
                 23 
                 ACAAGCATCTGAC 
                 24 
               
               
                 group F, 
                 NM_010151 
                   
                   
                 GTGAATAGC 
               
               
                 member 1 
               
               
                 (Nr2f1/COUP- 
               
               
                 TFI) 
               
               
                   
               
               
                 Glypican 4 
                 Human: 
                 GCAAGGTCTCCGTGGTAAACC 
                 25 
                 CCGGCAGTGGG 
                 26 
               
               
                 (Gpc4) 
                 NM_001448 
                   
                   
                 AGCAGTA 
               
               
                   
                 Murine: 
                 GGCAGCTGGCACTAGTTTG 
                 27 
                 AACGGTGCTTGG 
                 28 
               
               
                   
                 NM_008150 
                   
                   
                 GAGAGAG 
               
               
                   
               
               
                 Thrombomodulin 
                 Human: 
                 CCCAACACCCAGGCTAGCT 
                 29 
                 GATGTCCGTGCA 
                 30 
               
               
                 (Thbd) 
                 NM_000361 
                   
                   
                 GATGAAACC 
               
               
                   
                 Murine: 
                 TCCCAAGTTTCCATGTTTCC 
                 31 
                 GCATGAGTTGTG 
                 32 
               
               
                   
                 NM_009378 
                   
                   
                 TGCTTCGT 
               
               
                   
               
               
                 Homeobox A5 
                 Human: 
                 CGCCCAACCCCAGATCTAC 
                 33 
                 CGGGCCGCCTATGTTGT 
                 34 
               
               
                 (HoxA5) 
                 NM_019102 
               
               
                   
                 Murine: 
                 CCCAGATCTACCCCTGGATG 
                 35 
                 CAGGGTCTGGT 
                 36 
               
               
                   
                 NM_010453 
                   
                   
                 AGCGAGTGT 
               
               
                   
               
               
                 Homeobox C8 
                 Human: 
                 ATGGATGAGACCCCACGCTC 
                 37 
                 AGACTTCAATC 
                 38 
               
               
                 (HoxC8) 
                 NM_022658 
                   
                   
                 CGACGTTTTCG 
               
               
                   
                 Murine: 
                 GTCTCCCAGCCTCATGTTTC 
                 39 
                 TCTGATACCGGC 
                 40 
               
               
                   
                 NM_010466 
                   
                   
                 TGTAAGTTTGT 
               
               
                   
               
               
                 36B4 
                 Human: 
                 AACATGCTCAACATCTCCCC-3 
                 41 
                 CCGACTCCTCC 
                 42 
               
               
                   
                 NM_001002 
                   
                   
                 GACTCTTC 
               
               
                   
               
               
                 TATA box- 
                 Murine: 
                 ACCCTTCACCAATGACTCCTATG 
                 43 
                 TGACTGCAGCA 
                 44 
               
               
                 binding protein 
                 NM_013684 
                   
                   
                 AATCGCTTGG 
               
               
                 (TBP) 
               
               
                   
               
            
           
         
       
     
     Example 3 
     Interdepot Differences in Gene Expression are Independent of Extrinsic Factors 
     To determine if these differences in gene expression were cell autonomous, preadipocytes (SVF) taken from intra-abdominal (epididymal) or subcutaneous adipose were placed in culture in defined serum free medium and subjected to in vitro differentiation. 
     Preadipocyte Differentiation 
     Induction of preadipocyte differentiation was performed using the stromovascular fraction as described by Hauner et al. (Lean, (2000) Proc Nutr Soc 59, 331-6). After 16 hours of incubation, cells were extensively washed with PBS, and the medium was changed into medium consisting on DMEM/F12 1:1 medium with antibiotics supplemented with 33 μM biotin, 17 μM panthotenate, 10 μg/ml human transferrin, 66 nM insulin, 1 nM triiodothyronine, 1 μM dexamethasone, and, for the first 3 days, 1 μg/ml troglitazone. The medium was then changed every 2 days. After 6 days of differentiation, cells were washed once with PBS before proceeding for RNA extraction). 
     After 6 days, all the predominantly subcutaneous genes and all the predominantly epididymal genes maintained their interdepot differences of expression  FIGS. 2C and 3C ). Thus, differences of developmental gene expression between depots are independent of extrinsic factors, such as innervation, blood flow, the level of oxygenation and nutrients or any other interstitial factors. 
     Example 4 
     Interdepot Differences of Expression in Humans 
     Since the striking interdepot differences for expression of these developmental genes between subcutaneous and intra-abdominal fat in mice appeared to be intrinsic and be present in both the preadipocyte and adipocyte fractions, we decided to determine if similar differences might be present in human adipose tissue. To address this question, 53 lean subjects (22 males and 31 females with BMI &lt;25) with normal fat distribution (WHR for male 0.80-1.06, WHR for female 0.62-0.87) were subjected to abdominal subcutaneous and visceral adipose tissue biopsies and gene expression for the human homologues of each of these developmental genes assessed using real time PCR. 
     Human Subjects 
     Paired samples of visceral and subcutaneous adipose tissue were obtained from 198 Caucasian men (n=99) and women (n=99) who underwent open abdominal surgery for gastric banding, cholecystectomy, appendectomy, weight reduction surgery, abdominal injury, or explorative laparotomy. The age ranged from 24 to 85 years for male and from 27 to 86 years for female. Body mass index (BMI) ranged from 21.7 to 46.8 kg/m 2  for the males and from 20.8 to 54.1 kg/m 2  for the females. Waist-to-hip ratio (WHR) ranged from 0.8 to 1.37 for the males and from 0.62 to 1.45 for the females. All subjects had a stable weight with no fluctuations of more than 2 percent of the body weight for at least 3 months before surgery. Patients with severe conditions including type 2 diabetes, generalized inflammation or end stage malignant diseases were excluded from the study. Samples of visceral and subcutaneous adipose tissue were immediately frozen in liquid nitrogen after removal. The study was approved by the ethics committee of the University of Leipzig. All subjects gave written informed consent before taking part in the study. 
     As observed in mice, Nr2f1, Thbd, HoxA5 and HoxC8, which showed higher expression in epididymal fat showed a higher level of expression in visceral adipose tissue of humans, both in males and females ( FIGS. 4F , G, H, and I, respectively). In addition, for these genes, the magnitude of interdepot differential gene expression in humans was even greater than that in mice Nr2f1461-fold and 894fold, Thbd 124-fold and 147-fold, HoxA5 23-fold and 24-fold, HoxC8 1210-fold and 1100-fold, for males and females, respectively). Glypican 4 (Gpc4) expression in humans also showed a strong differential expression, however in lean humans this gene was more highly expressed in subcutaneous as compared to visceral adipose tissue with a 5.4-fold difference in males and 4.8-fold difference in females ( FIG. 43 ). 
     The group of subcutaneous genes also showed significant and differential patterns of expression between depots in humans. In this case, two of the genes, Shox2 and En1, presented a pattern of expression in humans in the same direction as in mice, and in the case of En1, the differential expression was of extreme magnitude (17,500-fold and 42,500-fold for males and females, respectively) ( FIGS. 4A-B ). As in mice, HoxC9 expression was found significantly higher in subcutaneous than in visceral adipose tissue (2.3-fold), however, in humans this difference was gender-specific and was not present in males ( FIG. 4C ). Tbx15 and Srfp2 also showed markedly different expression in humans, however in humans these genes were more highly expressed in visceral adipose tissue compared to subcutaneous adipose tissue in both genders (Tbx15: 27.1-fold in male and 38.7-fold in female, Sfrp2: 950-fold in male and 1200-fold in female) ( FIGS. 4D-E ). 
     Example 5 
     Gene Expression, BMI and Body Fat Distribution 
     To investigate whether the genes studied were related to obesity or body fat distribution, we determined the level of gene expression in adipose tissue biopsies from this group of 53 subjects plus another group of 145 overweight or obese individuals. The final group of 198 human subjects (99 males and 99 females) ranged from lean to obese (BMI range 21.7-46.8 for male and 20.8-54.1 for female) with variable adipose tissue distribution (Waist-Hip Ratio [WHR] 0.8-1.37 for males and 0.62-1.45 for females) (Table 4). Three of the 10 developmental genes showed significant relationships to BMI or OHR. HoxA5 expression in both visceral and subcutaneous adipose tissue significantly increased with BMI in males (R=0.448, p &lt;0.0001 and, R=0.292, p=0.0034, respectively) and females (R=0.535, p&lt;0.0001 and R=0.361, p=0.0002, respectively) ( FIG. 5A ). This correlation was more marked in visceral than in subcutaneous adipose tissue in both genders. In addition, there was a significant positive correlation of UoxA5 expression with WER in visceral and subcutaneous adipose tissue for both males (R=0.446, p&lt;0.0001 and R=0.479, p&lt;0.0001, respectively) and females (R=0.580, p&lt;0.0001 and R=0.449, p&lt;0.0001, respectively) ( FIG. 5B ). 
     In human adipose, there were very strong correlations of Gpc4 expression with BMI and WHR in both males and females. In this case, the correlation in the two depots was in opposite directions with decreasing Gp4 expression in subcutaneous adipose tissue with increasing BMI (male: R=0.74, p&lt;0.0001; female. R=0.735, p &lt;0.0001) and WHR (male: R=0.575, p&lt;0.0001; female: R=0.730, p&lt;0.0001), and increasing Gpc4 expression in visceral adipose tissue with increasing BMI (male: R=0.525, p&lt;0.0001; female: R=0.507, p&lt;0.0001) and WHR (male: R=0.598, p &lt;0.0001; female: R=0.5, p&lt;0.0001) ( FIGS. 5A-B ). In addition, the shape of the relationship was different, being fairly linear in visceral adipose tissue, whereas in subcutaneous adipose tissue Gpc4 expression decreased abruptly as individual when from normal BMI (20-25) to overweight (BMI&gt;25) or obese (BMI&gt;30) levels. Likewise, in subcutaneous adipose tissue Gpc4 expression displayed a curvilinear negative correlation with very low levels in males with WHR&gt;1.1 and females with WHR&gt;0.95. 
     The most profound correlations with BMI and WHR were observed for Tbx15 expression in visceral adipose tissue. As with Gpc4, there was a strong exponential negative relationship with a marked decrease in Tbx15 expression as BMI progressed from normal to overweight or obese levels. This was true in both males (R=0.706, p &lt;0.0001) and females R=0.852, p&lt;0.0001) ( FIG. 5A ). There was also a strong exponential negative relationship between Tbox15 expression and WHR in visceral adipose tissue with marked declines above WHR of 1.05 for males (R=0.604, p&lt;0.0001) and 0.95 for females (R=0.817, p&lt;0.0001) ( FIG. 5B ). By contrast, Tbx15 expression showed a more modest positive correlation with both BMI and WHR in subcutaneous adipose tissue of both males (R=0.282, p=0.0047; R=0.406, p&lt;0.0001) and females (R=0.191, p=0.0587; R=0.345, p=0.0005). However, in all cases, expression of Tbx15 in subcutaneous tissue was much lower than the level of expression in visceral adipose tissue of lean individuals. Thus, HoxA5, Gpc4 and Tbx15 expression in adipose tissue were strongly correlated with the level of obesity, as well as adipose tissue distribution, especially Tbx15 expression in visceral fat. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Characteristics of the Study Population 
               
            
           
           
               
               
               
            
               
                 Gender 
                 Male (98 subjects) 
                 Female (98 subjects) 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Mean age ± SD (range) years 
                 56.4 ± 13.3 
                 (25-85) 
                 56 ± 16.6 
                 (27-86) 
               
               
                 Mean BMI ± SD (range) 
                 30.8 ± 6.7 
                 (21.7-46.8) 
                 31 ± 7.6 
                 (20.8-54.1) 
               
               
                 Mean WHR ± SD (range) 
                 1.07 ± 0.12 
                 (0.8-1.37) 
                 0.94 ± 0.19 
                 (0.62-1.45) 
               
               
                 Mean fasted Insulin level ± SD (range) pM 
                 128.8 ± 119.2 
                 (12-512) 
                 137.6 ± 129 
                 (10.5-628) 
               
               
                 Mean fasted FFA level ± SD (range) mM 
                 0.53 ± 0.34 
                 (0.05-1.51) 
                 0.53 ± 0.32 
                 (0.05-1.31) 
               
               
                   
               
            
           
         
       
     
     Other Embodiments 
     It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.