Population Differences in Transcript-Regulator Expression Quantitative Trait LociReportar como inadecuado

Population Differences in Transcript-Regulator Expression Quantitative Trait Loci - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Gene expression quantitative trait loci eQTL are useful for identifying single nucleotide polymorphisms SNPs associated with diseases. At times, a genetic variant may be associated with a master regulator involved in the manifestation of a disease. The downstream target genes of the master regulator are typically co-expressed and share biological function. Therefore, it is practical to screen for eQTLs by identifying SNPs associated with the targets of a transcript-regulator TR. We used a multivariate regression with the gene expression of known targets of TRs and SNPs to identify TReQTLs in European CEU and African YRI HapMap populations. A nominal p-value of <1×10−6 revealed 234 SNPs in CEU and 154 in YRI as TReQTLs. These represent 36 independent tag SNPs in CEU and 39 in YRI affecting the downstream targets of 25 and 36 TRs respectively. At a false discovery rate FDR = 45%, one cis-acting tag SNP within 1 kb of a gene in each population was identified as a TReQTL. In CEU, the SNP rs16858621 in Pcnxl2 was found to be associated with the genes regulated by CREM whereas in YRI, the SNP rs16909324 was linked to the targets of miRNA hsa-miR-125a. To infer the pathways that regulate expression, we ranked TReQTLs by connectivity within the structure of biological process subtrees. One TReQTL SNP rs3790904 in CEU maps to Lphn2 and is associated nominal p-value = 8.1×10−7 with the targets of the X-linked breast cancer suppressor Foxp3. The structure of the biological process subtree and a gene interaction network of the TReQTL revealed that tumor necrosis factor, NF-kappaB and variants in G-protein coupled receptors signaling may play a central role as communicators in Foxp3 functional regulation. The potential pleiotropic effect of the Foxp3 TReQTLs was gleaned from integrating mRNA-Seq data and SNP-set enrichment into the analysis.

Autor: Pierre R. Bushel , Ray McGovern, Liwen Liu, Oliver Hofmann, Ahsan Huda, Jun Lu, Winston Hide, Xihong Lin

Fuente: http://plos.srce.hr/


Documentos relacionados