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Bimodal distribution of RNA expression levels in human skeletal muscle tissue

Bimodal distribution of RNA expression levels in human skeletal muscle tissue,10.1186/1471-2164-12-98,BMC Genomics,Clinton C Mason,Robert L Hanson,Vic

Bimodal distribution of RNA expression levels in human skeletal muscle tissue   (Citations: 2)
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BACKGROUND: Many human diseases and phenotypes are related to RNA expression, levels of which are influenced by a wide spectrum of genetic and exposure-related factors. In a large genome-wide study of muscle tissue expression, we found that some genes exhibited a bimodal distribution of RNA expression, in contrast to what is usually assumed in studies of a single healthy tissue. As bimodality has classically been considered a hallmark of genetic control, we assessed the genome-wide prevalence, cause, and association of this phenomenon with diabetes-related phenotypes in skeletal muscle tissue from 225 healthy Pima Indians using exon array expression chips. RESULTS: Two independent batches of microarrays were used for bimodal assessment and comparison. Of the 17,881 genes analyzed, eight (GSTM1, HLA-DRB1, ERAP2, HLA-DRB5, MAOA, ACTN3, NR4A2, and THNSL2) were found to have bimodal expression replicated in the separate batch groups, while 24 other genes had evidence of bimodality in only one group. Some bimodally expressed genes had modest associations with pre-diabetic phenotypes, of note ACTN3 with insulin resistance. Most of the other bimodal genes have been reported to be involved with various other diseases and characteristics. Association of expression with cis genetic variation in a subset of 149 individuals found all but one of the confirmed bimodal genes and nearly half of all potential ones to be highly significant expression quantitative trait loci (eQTL). The rare prevalence of these bimodally expressed genes found after controlling for batch effects was much lower than the prevalence reported in other studies. Additional validation in data from separate muscle expression studies confirmed the low prevalence of bimodality we observed. CONCLUSIONS: We conclude that the prevalence of bimodal gene expression is quite rare in healthy muscle tissue (cis-polymorphisms, indicating that such bimodal genes are, for the most part, eQTL. The high frequency of disease associations reported with these genes gives hope that this unique feature may identify or actually be an underlying factor responsible for disease development.
Journal: BMC Genomics , vol. 12, no. 1, pp. 98-16, 2011
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    • ..., thought to occur due to cis-acting polymorphisms ...

    Caroline S. Foxet al. Genome-Wide Association for Abdominal Subcutaneous and Visceral Adipos...

    • ...The expression levels of several skeletal muscle mRNA transcripts in the exon array study had a bimodal frequency distribution, and these transcripts were found to be highly significant expression quantitative trait loci (eQTL), one of which was transcribed from HLA-DRB1 [10]...
    • ...The parameters of the best-fitting bimodal distribution were estimated by maximum likelihood methods after transforming expression data to correct for skewness using the most appropriate Box–Cox parameter, as previously described [10, 21]...
    • ...Individuals were classified into high and low expression categories of HLA-DRB1 based on these parameters [10]...

    R. C. Williamset al. HLA-DRB1 reduces the risk of type 2 diabetes mellitus by increased ins...

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