Exon-specific QTLs skew the inferred distribution of expression QTLs detected using gene expression array data.

PloS One
Jean-Baptiste VeyrierasJonathan K Pritchard

Abstract

Mapping of expression quantitative trait loci (eQTLs) is an important technique for studying how genetic variation affects gene regulation in natural populations. In a previous study using Illumina expression data from human lymphoblastoid cell lines, we reported that cis-eQTLs are especially enriched around transcription start sites (TSSs) and immediately upstream of transcription end sites (TESs). In this paper, we revisit the distribution of eQTLs using additional data from Affymetrix exon arrays and from RNA sequencing. We confirm that most eQTLs lie close to the target genes; that transcribed regions are generally enriched for eQTLs; that eQTLs are more abundant in exons than introns; and that the peak density of eQTLs occurs at the TSS. However, we find that the intriguing TES peak is greatly reduced or absent in the Affymetrix and RNA-seq data. Instead our data suggest that the TES peak observed in the Illumina data is mainly due to exon-specific QTLs that affect 3' untranslated regions, where most of the Illumina probes are positioned. Nonetheless, we do observe an overall enrichment of eQTLs in exons versus introns in all three data sets, consistent with an important role for exonic sequences in gene regulation.

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Citations

Jul 13, 2013·Genome Biology·Anat Kreimer, Itsik Pe'er
Nov 20, 2015·Molecular Biology and Evolution·Johannes EngelkenElena Bosch
Mar 5, 2016·Human Molecular Genetics·Darren A CusanovichCarole Ober
Aug 11, 2016·PloS One·Michael A GrassiUNKNOWN DCCT/EDIC Research Group
Dec 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ryosuke KitaHunter B Fraser

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Methods Mentioned

BETA
RNA-seq

Software Mentioned

EN
Ensembl
MAQ
Affymetrix
BIMBAM
LARS

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