Genome-wide epistatic expression quantitative trait loci discovery in four human tissues reveals the importance of local chromosomal interactions governing gene expression

BMC Genomics
Darren J FitzpatrickDenis C Shields

Abstract

Epistasis (synergistic interaction) among SNPs governing gene expression is likely to arise within transcriptional networks. However, the power to detect it is limited by the large number of combinations to be tested and the modest sample sizes of most datasets. By limiting the interaction search space firstly to cis-trans and then cis-cis SNP pairs where both SNPs had an independent effect on the expression of the most variable transcripts in the liver and brain, we greatly reduced the size of the search space. Within the cis-trans search space we discovered three transcripts with significant epistasis. Surprisingly, all interacting SNP pairs were located nearby each other on the chromosome (within 290 kb-2.16 Mb). Despite their proximity, the interacting SNPs were outside the range of linkage disequilibrium (LD), which was absent between the pairs (r(2) < 0.01). Accordingly, we redefined the search space to detect cis-cis interactions, where a cis-SNP was located within 10 Mb of the target transcript. The results of this show evidence for the epistatic regulation of 50 transcripts across the tissues studied. Three transcripts, namely, HLA-G, PSORS1C1 and HLA-DRB5 share common regulatory SNPs in the pre-frontal cortex and thei...Continue Reading

References

Jun 22, 2001·Trends in Genetics : TIG·R C Jansen, J P Nap
Jul 22, 2004·Nature Reviews. Genetics·Orjan Carlborg, Chris S Haley
Jul 23, 2004·Nature·Michael MorleyVivian G Cheung
Dec 30, 2004·Nature Genetics·Jason H Moore
Dec 30, 2006·PLoS Genetics·Nick PattersonDavid Reich
Feb 10, 2007·Science·Barbara E StrangerEmmanouil T Dermitzakis
Jul 20, 2007·PloS One·Rudi AlbertsRitsert C Jansen
Sep 18, 2007·Nature Genetics·Barbara E StrangerEmmanouil T Dermitzakis
Sep 18, 2007·Nature Genetics·Harald H H GöringJohn Blangero
Sep 18, 2007·Nature Genetics·Anna L DixonWilliam O C Cookson
Mar 18, 2008·Nature·Valur EmilssonKari Stefansson
Mar 29, 2008·Science·Job Dekker
May 9, 2008·PLoS Biology·Eric E SchadtRoger Ulrich
Oct 11, 2008·PLoS Genetics·Jean-Baptiste VeyrierasJonathan K Pritchard
May 13, 2009·Nature Reviews. Genetics·Heather J Cordell
Aug 1, 2009·Science·Antigone S DimasStylianos E Antonarakis
Sep 8, 2009·American Journal of Human Genetics·Jason H Moore, Scott M Williams
Dec 8, 2009·Nature Genetics·Youssef IdaghdourGreg Gibson
Jan 23, 2010·Science·Michael CostanzoCharles Boone
Sep 22, 2010·PLoS Biology·Vivian G CheungRichard S Spielman
Oct 15, 2010·Nature Biotechnology·Bradley E BernsteinJames A Thomson
Jan 11, 2011·Bioinformatics·V M LourençoM Kirst
Mar 29, 2011·Briefings in Bioinformatics·Kristel Van Steen
Oct 21, 2011·Nature·David BrawandHenrik Kaessmann
Jun 12, 2012·Molecular Cell·Colm J RyanNevan J Krogan
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Sep 8, 2012·Nature·Robert E ThurmanJohn A Stamatoyannopoulos
Sep 8, 2012·Nature·Amartya SanyalJob Dekker

❮ Previous
Next ❯

Citations

Sep 7, 2016·Molecular Brain·Alejandro Medrano-Fernández, Angel Barco
Apr 25, 2018·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Bertrand LecointreA Ganesan

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM06990
GSE44771

Methods Mentioned

BETA
RNAseq
Hi-C
HiC
genotyping

Software Mentioned

PLINK
HaploReg
UCSC LiftOver tool
R
EIGENSOFT
smartpca

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik
Tobias WürschumJochen Christoph Reif
European Journal of Human Genetics : EJHG
Xing XuRobert J Klein
© 2021 Meta ULC. All rights reserved