Toward a more uniform sampling of human genetic diversity: a survey of worldwide populations by high-density genotyping.

High-throughput genotyping data are useful for making inferences about human evolutionary history. However, the populations sampled to date are unevenly distributed, and some areas (e.g., South and Central Asia) have rarely been sampled in large-scale studies. To assess human genetic variation more evenly, we sampled 296 individuals from 13 worldwide populations that are not covered by previous studies. By combining these samples with a data set from our laboratory and the HapMap II samples, we assembled a final dataset of ~250,000 SNPs in 850 individuals from 40 populations. With more uniform sampling, the estimate of global genetic differentiation (F(ST)) substantially decreases from ~16% with the HapMap II samples to ~11%. A panel of copy number variations typed in the same populations shows patterns of diversity similar to the SNP data, with highest diversity in African populations. This unique sample collection also permits new inferences about human evolutionary history. The comparison of haplotype variation among populations supports a single out-of-Africa migration event and suggests that the founding population of Eurasia may have been relatively large but isolated from Africans for a period of time. We also found a substantial affinity between populations from central Asia (Kyrgyzstani and Mongolian Buryat) and America, suggesting a central Asian contribution to New World founder populations.

[1]  Rui Mei,et al.  Large-scale SNP analysis reveals clustered and continuous patterns of human genetic variation , 2005, Human Genomics.

[2]  B. Weir,et al.  ESTIMATING F‐STATISTICS FOR THE ANALYSIS OF POPULATION STRUCTURE , 1984, Evolution; international journal of organic evolution.

[3]  Ryan D. Hernandez,et al.  Inferring the Joint Demographic History of Multiple Populations from Multidimensional SNP Frequency Data , 2009, PLoS genetics.

[4]  M. Miyamoto,et al.  Updated Three-Stage Model for the Peopling of the Americas , 2008, PloS one.

[5]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[6]  F. Salzano,et al.  Mitochondrial population genomics supports a single pre-Clovis origin with a coastal route for the peopling of the Americas. , 2008, American journal of human genetics.

[7]  K. Frazer,et al.  Common deletions and SNPs are in linkage disequilibrium in the human genome , 2006, Nature Genetics.

[8]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[9]  James J. Cai.  PGEToolbox: A Matlab toolbox for population genetics and evolution. , 2008, The Journal of heredity.

[10]  Anton Nekrutenko,et al.  Complete Khoisan and Bantu genomes from southern , 2010 .

[11]  P. Goldberg,et al.  ESR dates for the hominid burial site of Es Skhul in Israel , 1989, Nature.

[12]  J. Stephens,et al.  The structure of common genetic variation in United States populations. , 2007, American journal of human genetics.

[13]  M. Olivier.  A haplotype map of the human genome. , 2003, Nature.

[14]  E. Suchman,et al.  The American Soldier: Adjustment During Army Life. , 1949 .

[15]  D. Schaid,et al.  Exact tests of Hardy-Weinberg equilibrium and homogeneity of disequilibrium across strata. , 2006, American journal of human genetics.

[16]  M. Nei,et al.  DNA polymorphism detectable by restriction endonucleases. , 1981, Genetics.

[17]  Joshua M Akey,et al.  Genomic signatures of positive selection in humans and the limits of outlier approaches. , 2006, Genome research.

[18]  Joshua M. Korn,et al.  Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs , 2008, Nature Genetics.

[19]  Scott M. Williams,et al.  The Genetic Structure and History of Africans and African Americans , 2009, Science.

[20]  David H. Alexander,et al.  Fast model-based estimation of ancestry in unrelated individuals. , 2009, Genome research.

[21]  M. Feldman,et al.  Worldwide Human Relationships Inferred from Genome-Wide Patterns of Variation , 2008 .

[22]  Jerilyn A. Walker,et al.  Genetic variation among world populations: inferences from 100 Alu insertion polymorphisms. , 2003, Genome research.

[23]  Pardis C Sabeti,et al.  Positive Natural Selection in the Human Lineage , 2006, Science.

[24]  Natalie M. Myres,et al.  Distinctive Paleo-Indian Migration Routes from Beringia Marked by Two Rare mtDNA Haplogroups , 2009, Current Biology.

[25]  Joseph T. Glessner,et al.  PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. , 2007, Genome research.

[26]  M. Hammer,et al.  Genetic evidence on the origins of Indian caste populations. , 2001, Genome research.

[27]  S. Boissinot,et al.  Human Population Genetic Structure and Diversity Inferred from Polymorphic L1(LINE-1) and Alu Insertions , 2006, Human Heredity.

[28]  J. Kere,et al.  Microsatellite diversity and the demographic history of modern humans. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[29]  S. Wright,et al.  Evolution in Mendelian Populations. , 1931, Genetics.

[30]  A. Torroni,et al.  Mitochondrial and Y-chromosome diversity of the Tharus (Nepal): a reservoir of genetic variation , 2009, BMC Evolutionary Biology.

[31]  J. Long,et al.  Population genetics, history, and health patterns in native americans. , 2004, Annual review of genomics and human genetics.

[32]  L. Quintana-Murci,et al.  Natural selection has driven population differentiation in modern humans , 2008, Nature Genetics.

[33]  M. Olivier.  A haplotype map of the human genome , 2003, Nature.

[34]  Jinchuan Xing,et al.  Genetic Evidence for High-Altitude Adaptation in Tibet , 2010, Science.

[35]  Keith C. Cheng,et al.  SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans , 2005, Science.

[36]  T. Goebel,et al.  The Late Pleistocene Dispersal of Modern Humans in the Americas , 2008, Science.

[37]  J. Hoffecker.  The spread of modern humans in Europe , 2009, Proceedings of the National Academy of Sciences.

[38]  D. O’Rourke,et al.  The Human Genetic History of the Americas: The Final Frontier , 2010, Current Biology.

[39]  D. Conrad,et al.  A high-resolution survey of deletion polymorphism in the human genome , 2006, Nature Genetics.

[40]  Mark D Shriver,et al.  Measuring European population stratification with microarray genotype data. , 2007, American journal of human genetics.

[41]  Alkes L. Price,et al.  Reconstructing Indian Population History , 2009, Nature.

[42]  Sohini Ramachandran,et al.  Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[43]  M. Feldman,et al.  Clines, Clusters, and the Effect of Study Design on the Inference of Human Population Structure , 2005, PLoS genetics.

[44]  Eduardo Barrientos,et al.  Analysis of genomic diversity in Mexican Mestizo populations to develop genomic medicine in Mexico , 2009, Proceedings of the National Academy of Sciences.

[45]  Jin Ok Yang,et al.  Mapping Human Genetic Diversity in Asia , 2009, Science.

[46]  Tom H. Pringle,et al.  Complete Khoisan and Bantu genomes from southern Africa , 2010, Nature.

[47]  R. J. Herrera,et al.  The Himalayas as a directional barrier to gene flow. , 2007, American journal of human genetics.

[48]  L. Excoffier,et al.  A statistical evaluation of models for the initial settlement of the american continent emphasizes the importance of gene flow with Asia. , 2010, Molecular biology and evolution.

[49]  Pablo Villoslada,et al.  Analysis and Application of European Genetic Substructure Using 300 K SNP Information , 2008, PLoS genetics.

[50]  Jinchuan Xing,et al.  Fine-scaled human genetic structure revealed by SNP microarrays. , 2009, Genome research.

[51]  F. Rothhammer,et al.  Distribution of the four founding lineage haplotypes in Native Americans suggests a single wave of migration for the New World. , 1995, American journal of physical anthropology.

[52]  R. Klein.  Darwin and the recent African origin of modern humans , 2009, Proceedings of the National Academy of Sciences.

[53]  R. J. Herrera,et al.  Genetic insights into the origins of Tibeto-Burman populations in the Himalayas , 2009, Journal of Human Genetics.

[54]  Philip L. F. Johnson,et al.  A Draft Sequence of the Neandertal Genome , 2010, Science.

[55]  D. Pinto,et al.  Copy-number variation in control population cohorts. , 2007, Human molecular genetics.

[56]  Mattias Jakobsson,et al.  Genetic Variation and Population Structure in Native Americans , 2007, PLoS genetics.

[57]  Joshua M. Korn,et al.  Integrated detection and population-genetic analysis of SNPs and copy number variation , 2008, Nature Genetics.

[58]  Jérôme Goudet,et al.  Going the distance: human population genetics in a clinal world. , 2007, Trends in genetics : TIG.

[59]  Zachary A. Szpiech,et al.  Genotype, haplotype and copy-number variation in worldwide human populations , 2008, Nature.

[60]  Pablo Villoslada,et al.  European Population Substructure: Clustering of Northern and Southern Populations , 2006, PLoS genetics.

[61]  Simon C. Potter,et al.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls , 2007, Nature.

[62]  M. Bamshad,et al.  Genetic variation in South Indian castes: evidence from Y-chromosome, mitochondrial, and autosomal polymorphisms , 2008, BMC Genetics.

[63]  E. Bermingham,et al.  Mitochondrial DNA analysis of Mongolian populations and implications for the origin of New World founders. , 1996, Genetics.

[64]  W S Watkins,et al.  The distribution of human genetic diversity: a comparison of mitochondrial, autosomal, and Y-chromosome data. , 2000, American journal of human genetics.

[65]  Amit R. Indap,et al.  Genes mirror geography within Europe , 2008, Nature.

[66]  David Reich,et al.  Discerning the Ancestry of European Americans in Genetic Association Studies , 2007, PLoS genetics.