Exon expression QTL (eeQTL) analysis highlights distant genomic variations associated with splicing regulation

Abstract

Alternative splicing is a ubiquitous mechanism of post-transcriptional regulation of gene expression and produces multiple isoforms from the same genes. Expression quantitative trait loci (eQTL) has been a major method for finding associations between gene expression and genomic variations. Differences in alternative splicing isoforms are resulted from differences in the expression of exons. We propose to use exon expression QTL (eeQTL) to study the genomic variations that are associated with splicing regulation. A stringent criterion was adopted to study gene-level eQTLs and exon-level eeQTLs for both cis- and trans- factors. From experiments on an RNA-sequencing (RNA-Seq) data set of HapMap samples, we observed that compared with eQTLs, more eeQTL trans-factors can be found than cis-factors, and many of the eeQTLs cannot be found at the gene level. This work highlights that the regulation of exons adds another layer of regulation on gene expression, and that eeQTL analysis is a new approach for investigating genome-wide genomic variations that are involved in the regulation of alternative splicing.

Graphical abstract

Keywords

eeQTL / eQTL / alternative splicing / trans-factor / association / regulation

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SUPPLEMENTARY MATERIALS

The supplementary materials can be found online with this article at DOI 10.1007/s40484-014-0031-9.

ACKNOWLEDGEMENTS

This work is partially supported by the National Basic Research Program of China (2012CB316504), the Hi-tech Research and Development Program of China (2012AA020401), NSFC Grant 91010016, and the National Institute of General Medical Sciences (R01GM097230).

COMPLIANCE WITH ETHICS GUIDELINES

The author Leying Guan, Qian Yang, Mengting Gu, Liang Chen and Xuegong Zhang declare that they have no conflict of interests.This article does not contain any studies with human or animal subjects performed by any of the authors.

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg