Allele-specific expression and eQTL analysis in mouse adipose tissue

BMC Genomics

Thomas A Drake³  Aldons J Lusis¹  Eleazar Eskin²  Atila van Nas¹  Lisa Martin¹  Farhad Hormozdiari²  Yehudit Hasin-Brumshtein¹ 

[1] Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA;Department of Computer Science, University of California, Los Angeles, CA 90095, USA;Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA

关键词: C57BL/6J;    DBA/2J;    DNase I hypersensitivity;    RNA-seq;    Adipose;    Allele Specific Expression;    eQTL;    Trans;    Cis;   

Others  :  1216590
DOI  :  10.1186/1471-2164-15-471

 received in 2013-11-15, accepted in 2014-05-07,  发布年份 2014

【 摘 要 】

Background

The simplest definition of cis-eQTLs versus trans, refers to genetic variants that affect expression in an allele specific manner, with implications on underlying mechanism. Yet, due to technical limitations of expression microarrays, the vast majority of eQTL studies performed in the last decade used a genomic distance based definition as a surrogate for cis, therefore exploring local rather than cis-eQTLs.

Results

In this study we use RNAseq to explore allele specific expression (ASE) in adipose tissue of male and female F1 mice, produced from reciprocal crosses of C57BL/6J and DBA/2J strains. Comparison of the identified cis-eQTLs, to local-eQTLs, that were obtained from adipose tissue expression in two previous population based studies in our laboratory, yields poor overlap between the two mapping approaches, while both local-eQTL studies show highly concordant results. Specifically, local-eQTL studies show ~60% overlap between themselves, while only 15-20% of local-eQTLs are identified as cis by ASE, and less than 50% of ASE genes are recovered in local-eQTL studies. Utilizing recently published ENCODE data, we also find that ASE genes show significant bias for SNPs prevalence in DNase I hypersensitive sites that is ASE direction specific.

Conclusions

We suggest a new approach to analysis of allele specific expression that is more sensitive and accurate than the commonly used fisher or chi-square statistics. Our analysis indicates that technical differences between the cis and local-eQTL approaches, such as differences in genomic background or sex specificity, account for relatively small fraction of the discrepancy. Therefore, we suggest that the differences between two eQTL mapping approaches may facilitate sorting of SNP-eQTL interactions into true cis and trans, and that a considerable portion of local-eQTL may actually represent trans interactions.

【 授权许可】

   
2014 Hasin-Brumshtein et al.; licensee BioMed Central Ltd.

【 图 表 】

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