Global patterns of cis variation in human cells revealed by high-density allelic expression analysis

被引：175

作者：

Ge, Bing ^{[2
]}

Pokholok, Dmitry K. ^{[3
]}

Kwan, Tony ^{[2
]}

Grundberg, Elin ^{[1
,2
,4
]}

Morcos, Lisanne ^{[1
,2
,4
]}

Verlaan, Dominique J. ^{[1
,2
,4
]}

Le, Jennie ^{[3
]}

Koka, Vonda ^{[2
]}

Lam, Kevin C. L. ^{[2
]}

Gagne, Vincent ^{[5
]}

Dias, Joana ^{[2
]}

Hoberman, Rose ^{[6
]}

Montpetit, Alexandre ^{[2
]}

Joly, Marie-Michele ^{[2
]}

Harvey, Edward J. ^{[7
]}

Sinnett, Daniel ^{[5
]}

Beaulieu, Patrick ^{[5
]}

Hamon, Robert ^{[5
]}

Graziani, Alexandru ^{[5
]}

Dewar, Ken ^{[1
,2
,4
]}

Harmsen, Eef ^{[2
]}

Majewski, Jacek ^{[1
,2
,4
]}

Goering, Harald H. H. ^{[8
]}

Naumova, Anna K. ^{[4
,9
]}

Blanchette, Mathieu ^{[5
]}

Gunderson, Kevin L. ^{[3
]}

Pastinen, Tomi ^{[1
,2
,4
]}

机构：

[1] McGill Univ, McGill Univ Hlth Ctr, Dept Human Genet, Montreal, PQ, Canada

[2] Genome Quebec Innovat Ctr, Montreal, PQ, Canada

[3] Illumina Inc, San Diego, CA USA

[4] McGill Univ, McGill Univ Hlth Ctr, Dept Med Genet, Montreal, PQ, Canada

[5] Univ Montreal, Hop St Justine, Montreal, PQ H3T 1C5, Canada

[6] Univ Montreal, Sch Comp Sci, Montreal, PQ, Canada

[7] Univ Montreal, Div Orthopaed Surg, McGill Univ Hlth Ctr, Montreal, PQ, Canada

[8] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA

[9] McGill Univ, Dept Obstet & Gynecol, Res Inst, McGill Univ Hlth Ctr, Montreal, PQ H3A 2T5, Canada

来源：

NATURE GENETICS | 2009年 / 41卷 / 11期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; HUMAN GENE-EXPRESSION; REGULATORY VARIATION; HUMAN HAPLOTYPES; DISEASE; DISCOVERY; VARIANTS; LOCI;

D O I：

10.1038/ng.473

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Cis-acting variants altering gene expression are a source of phenotypic differences. The cis-acting components of expression variation can be identified through the mapping of differences in allelic expression (AE), which is the measure of relative expression between two allelic transcripts. We generated a map of AE associated SNPs using quantitative measurements of AE on Illumina Human1M BeadChips. In 53 lymphoblastoid cell lines derived from donors of European descent, we identified common cis variants affecting 30% (2935/9751) of the measured RefSeq transcripts at 0.001 permutation significance. The pervasive influence of cis-regulatory variants, which explain >50% of population variation in AE, extend to full-length transcripts and their isoforms as well as to unannotated transcripts. These strong effects facilitate fine mapping of cis-regulatory SNPs, as demonstrated by dissection of heritable control of transcripts in the systemic lupus erythematosus-associated C8orf13-BLK region in chromosome 8. The dense collection of associations will facilitate large-scale isolation of cis-regulatory SNPs.

引用

页码：1216 / U78

页数：9

共 29 条

[1] Global Survey of Genomic Imprinting by Transcriptome Sequencing [J].

Babak, Tomas ;

DeVeale, Brian ;

Armour, Christopher ;

Raymond, Christopher ;

Cleary, Michele A. ;

van der Kooy, Derek ;

Johnson, Jason M. ;

Lim, Lee P. .

CURRENT BIOLOGY, 2008, 18 (22) :1735-1741

[2] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[3] Validating Discovered Cis-Acting Regulatory Genetic Variants: Application of an Allele Specific Expression Approach to HapMap Populations [J].

Campino, Susana ;

Forton, Julian ;

Raj, Srilakshmi ;

Mohr, Bert ;

Auburn, Sarah ;

Fry, Andrew ;

Mangano, Valentina D. ;

Vandiedonck, Claire ;

Richardson, Anna ;

Rockett, Kirk ;

Clark, Taane G. ;

Kwiatkowski, Dominic P. .

PLOS ONE, 2008, 3 (12)

[4] Mapping determinants of human gene expression by regional and genome-wide association [J].

Cheung, VG ;

Spielman, RS ;

Ewens, KG ;

Weber, TM ;

Morley, M ;

Burdick, JT .

NATURE, 2005, 437 (7063) :1365-1369

[5] Monozygotic twins reveal germline contribution to allelic expression differences [J].

Cheung, Vivian G. ;

Bruzel, Alan ;

Burdick, Joshua T. ;

Morley, Michael ;

Devlin, James L. ;

Spielman, Richard S. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (06) :1357-1360

[6] Genetic Analysis of Human Traits In Vitro: Drug Response and Gene Expression in Lymphoblastoid Cell Lines [J].

Choy, Edwin ;

Yelensky, Roman ;

Bonakdar, Sasha ;

Plenge, Robert M. ;

Saxena, Richa ;

De Jager, Philip L. ;

Shaw, Stanley Y. ;

Wolfish, Cara S. ;

Slavik, Jacqueline M. ;

Cotsapas, Chris ;

Rivas, Manuel ;

Dermitzakis, Emmanouil T. ;

Cahir-McFarland, Ellen ;

Kieff, Elliott ;

Hafler, David ;

Daly, Mark J. ;

Altshuler, David .

PLOS GENETICS, 2008, 4 (11)

[7] Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci [J].

Cooper, Jason D. ;

Smyth, Deborah J. ;

Smiles, Adam M. ;

Plagnol, Vincent ;

Walker, Neil M. ;

Allen, James E. ;

Downes, Kate ;

Barrett, Jeffrey C. ;

Healy, Barry C. ;

Mychaleckyj, Josyf C. ;

Warram, James H. ;

Todd, John A. .

NATURE GENETICS, 2008, 40 (12) :1399-1401

[8] Common Regulatory Variation Impacts Gene Expression in a Cell Type-Dependent Manner [J].

Dimas, Antigone S. ;

Deutsch, Samuel ;

Stranger, Barbara E. ;

Montgomery, Stephen B. ;

Borel, Christelle ;

Attar-Cohen, Homa ;

Ingle, Catherine ;

Beazley, Claude ;

Arcelus, Maria Gutierrez ;

Sekowska, Magdalena ;

Gagnebin, Marilyne ;

Nisbett, James ;

Deloukas, Panos ;

Dermitzakis, Emmanouil T. ;

Antonarakis, Stylianos E. .

SCIENCE, 2009, 325 (5945) :1246-1250

[9] A genome-wide association study of global gene expression [J].

Dixon, Anna L. ;

Liang, Liming ;

Moffatt, Miriam F. ;

Chen, Wei ;

Heath, Simon ;

Wong, Kenny C. C. ;

Taylor, Jenny ;

Burnett, Edward ;

Gut, Ivo ;

Farrall, Martin ;

Lathrop, G. Mark ;

Abecasis, Goncalo R. ;

Cookson, William O. C. .

NATURE GENETICS, 2007, 39 (10) :1202-1207

[10] Genetics of gene expression and its effect on disease [J].

Emilsson, Valur ;

Thorleifsson, Gudmar ;

Zhang, Bin ;

Leonardson, Amy S. ;

Zink, Florian ;

Zhu, Jun ;

Carlson, Sonia ;

Helgason, Agnar ;

Walters, G. Bragi ;

Gunnarsdottir, Steinunn ;

Mouy, Magali ;

Steinthorsdottir, Valgerdur ;

Eiriksdottir, Gudrun H. ;

Bjornsdottir, Gyda ;

Reynisdottir, Inga ;

Gudbjartsson, Daniel ;

Helgadottir, Anna ;

Jonasdottir, Aslaug ;

Jonasdottir, Adalbjorg ;

Styrkarsdottir, Unnur ;

Gretarsdottir, Solveig ;

Magnusson, Kristinn P. ;

Stefansson, Hreinn ;

Fossdal, Ragnheidur ;

Kristjansson, Kristleifur ;

Gislason, Hjortur G. ;

Stefansson, Tryggvi ;

Leifsson, Bjorn G. ;

Thorsteinsdottir, Unnur ;

Lamb, John R. ;

Gulcher, Jeffrey R. ;

Reitman, Marc L. ;

Kong, Augustine ;

Schadt, Eric E. ;

Stefansson, Kari .

NATURE, 2008, 452 (7186) :423-U2

← 1 2 3 →