title: Genotype, haplotype and copy-number variation in worldwide human populations.
abstract: Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups. Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms (SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected--including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas--the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.
authors.affiliation: Center for Computational Medicine and Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Mattias
authors.initials: M
authors.lastname: Jakobsson
authors.forename: Sonja W
authors.initials: SW
authors.lastname: Scholz
authors.forename: Paul
authors.initials: P
authors.lastname: Scheet
authors.forename: J Raphael
authors.initials: JR
authors.lastname: Gibbs
authors.forename: Jenna M
authors.initials: JM
authors.lastname: VanLiere
authors.forename: Hon-Chung
authors.initials: HC
authors.lastname: Fung
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Szpiech
authors.forename: James H
authors.initials: JH
authors.lastname: Degnan
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Rita
authors.initials: R
authors.lastname: Guerreiro
authors.forename: Jose M
authors.initials: JM
authors.lastname: Bras
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Schymick
authors.forename: Dena G
authors.initials: DG
authors.lastname: Hernandez
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.forename: Javier
authors.initials: J
authors.lastname: Simon-Sanchez
authors.forename: Mar
authors.initials: M
authors.lastname: Matarin
authors.forename: Angela
authors.initials: A
authors.lastname: Britton
authors.forename: Joyce
authors.initials: J
authors.lastname: van de Leemput
authors.forename: Ian
authors.initials: I
authors.lastname: Rafferty
authors.forename: Maja
authors.initials: M
authors.lastname: Bucan
authors.forename: Howard M
authors.initials: HM
authors.lastname: Cann
authors.forename: John A
authors.initials: JA
authors.lastname: Hardy
authors.forename: Noah A
authors.initials: NA
authors.lastname: Rosenberg
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
mesh_terms: D000349:Africa; D000483:Alleles; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005828:Genetics, Population; D015894:Genome, Human / Q000235:genetics*; D005843:Geography; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide / Q000235:genetics