Gene-expression variation within and among human populations

被引:221
作者
Storey, John D.
Madeoy, Jennifer
Strout, Jeanna L.
Wurfel, Mark
Ronald, James
Akey, Joshua M.
机构
[1] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
[2] Univ Washington, Dept Biostat, Seattle, WA 98195 USA
[3] Univ Washington, Div Pulm & Crit Care Med, Harborview Med Ctr, Seattle, WA 98195 USA
关键词
D O I
10.1086/512017
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Understanding patterns of gene-expression variation within and among human populations will provide important insights into the molecular basis of phenotypic diversity and the interpretation of patterns of expression variation in disease. However, little is known about how gene-expression variation is apportioned within and among human populations. Here, we characterize patterns of natural gene-expression variation in 16 individuals of European and African ancestry. We find extensive variation in gene-expression levels and estimate that similar to 83% of genes are differentially expressed among individuals and that similar to 17% of genes are differentially expressed among populations. By decomposing total gene-expression variation into within-versus among-population components, we find that most expression variation is due to variation among individuals rather than among populations, which parallels observations of extant patterns of human genetic variation. Finally, we performed allele-specific quantitative polymerase chain reaction to demonstrate that cis-regulatory variation in the lymphocyte adaptor protein (SH2B adapter protein 3) contributes to differential expression between European and African samples. These results provide the first insight into how human population structure manifests itself in gene-expression levels and will help guide the search for regulatory quantitative trait loci.
引用
收藏
页码:502 / 509
页数:8
相关论文
共 45 条
[1]   Population history and natural selection shape patterns of genetic variation in 132 genes [J].
Akey, JM ;
Eberle, MA ;
Rieder, MJ ;
Carlson, CS ;
Shriver, MD ;
Nickerson, DA ;
Kruglyak, L .
PLOS BIOLOGY, 2004, 2 (10) :1591-1599
[2]   Interrogating a high-density SNP map for signatures of natural selection [J].
Akey, JM ;
Zhang, G ;
Zhang, K ;
Jin, L ;
Shriver, MD .
GENOME RESEARCH, 2002, 12 (12) :1805-1814
[3]   A haplotype map of the human genome [J].
Altshuler, D ;
Brooks, LD ;
Chakravarti, A ;
Collins, FS ;
Daly, MJ ;
Donnelly, P ;
Gibbs, RA ;
Belmont, JW ;
Boudreau, A ;
Leal, SM ;
Hardenbol, P ;
Pasternak, S ;
Wheeler, DA ;
Willis, TD ;
Yu, FL ;
Yang, HM ;
Zeng, CQ ;
Gao, Y ;
Hu, HR ;
Hu, WT ;
Li, CH ;
Lin, W ;
Liu, SQ ;
Pan, H ;
Tang, XL ;
Wang, J ;
Wang, W ;
Yu, J ;
Zhang, B ;
Zhang, QR ;
Zhao, HB ;
Zhao, H ;
Zhou, J ;
Gabriel, SB ;
Barry, R ;
Blumenstiel, B ;
Camargo, A ;
Defelice, M ;
Faggart, M ;
Goyette, M ;
Gupta, S ;
Moore, J ;
Nguyen, H ;
Onofrio, RC ;
Parkin, M ;
Roy, J ;
Stahl, E ;
Winchester, E ;
Ziaugra, L ;
Shen, Y .
NATURE, 2005, 437 (7063) :1299-1320
[4]   An apportionment of human DNA diversity [J].
Barbujani, G ;
Magagni, A ;
Minch, E ;
CavalliSforza, LL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (09) :4516-4519
[5]   Cis-acting variation in the expression of a high proportion of genes in human brain [J].
Bray, NJ ;
Buckland, PR ;
Owen, MJ ;
O'Donovan, MC .
HUMAN GENETICS, 2003, 113 (02) :149-153
[6]   A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain [J].
Bray, NJ ;
Buckland, PR ;
Williams, NM ;
Williams, HJ ;
Norton, N ;
Owen, MJ ;
O'Donovan, MC .
AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (01) :152-161
[7]   Observations on the swarming and mating behaviour of Anopheles funestus from southern Mozambique -: art. no. 2 [J].
Charlwood, JD ;
Thompson, R ;
Madsen, H .
MALARIA JOURNAL, 2003, 2 (1)
[8]   Natural variation in human gene expression assessed in lymphoblastoid cells [J].
Cheung, VG ;
Conlin, LK ;
Weber, TM ;
Arcaro, M ;
Jen, KY ;
Morley, M ;
Spielman, RS .
NATURE GENETICS, 2003, 33 (03) :422-425
[9]   The-374A allele of the receptor for advanced glycation end products gene is associated with a decreased risk of ischemic heart disease in African-Brazilians with type 2 diabetes [J].
dos Santos, KG ;
Canani, LH ;
Gross, JL ;
Tschiedel, B ;
Souto, KEP ;
Rolsenberg, S .
MOLECULAR GENETICS AND METABOLISM, 2005, 85 (02) :149-156
[10]   Cis-acting expression quantitative trait loci in mice [J].
Doss, S ;
Schadt, EE ;
Drake, TA ;
Lusis, AJ .
GENOME RESEARCH, 2005, 15 (05) :681-691