title: Gene-expression variation within and among human populations.
abstract: 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 approximately 83% of genes are differentially expressed among individuals and that approximately 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.
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195-7730, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Storey
authors.forename: Jennifer
authors.initials: J
authors.lastname: Madeoy
authors.forename: Jeanna L
authors.initials: JL
authors.lastname: Strout
authors.forename: Mark
authors.initials: M
authors.lastname: Wurfel
authors.forename: James
authors.initials: J
authors.lastname: Ronald
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Akey
mesh_terms: D044466:Asian People / Q000235:genetics; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005828:Genetics, Population; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D040641:Quantitative Trait Loci; D014158:Transcription, Genetic; D044465:White People / Q000235:genetics