The Population Genetics of Quechuas, the Largest Native South American Group: Autosomal Sequences, SNPs, and Microsatellites Evidence High Level of Diversity Marilia O. Scliar, 1y Giordano B. Soares-Souza, 1y Juliana Chevitarese, 1 Livia Lemos, 1 Wagner C.S. Magalha ˜ es, 1 Nelson J. Fagundes, 2 Sandro L. Bonatto, 3 Meredith Yeager, 4,5 Stephen J. Chanock, 6 and Eduardo Tarazona-Santos 1 * 1 Departamento de Biologia Geral, Instituto de Cie ˆncias Biolo ´gicas, Universidade Federal de Minas Gerais. Av. Antonio Carlos 6627, Pampulha. Caixa Postal 486, Belo Horizonte, Minas Gerais, CEP 31270-910, Brazil 2 Departamento de Gene ´tica, Instituto de Biocie ˆncias, Universidade Federal do Rio Grande do Sul, Caixa Postal 15053, Porto Alegre, Rio Grande do Sul, CEP 91501-970, Brazil 3 Faculdade de Biocie ˆncias, Pontifı´cia Universidade Cato ´lica do Rio Grande do Sul, Av. Ipiranga 6681, Caixa Postal 1429, Porto Alegre, Rio Grande do Sul, CEP 90619-900, Brazil 4 Intramural Research Support Program, SAIC Frederick, NCI-FCRDC, Frederick, MD 21702 5 Core Genotype Facility, NCI, NIH, Gaithersburg, MD 6 Laboratory of Translational Genomics of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Gaithersburg, MD 20877 KEY WORDS native American; Andes; microsatellites; autosomal noncoding sequence; HGDP– CEPH ABSTRACT Elucidating the pattern of genetic diver- sity for non-European populations is necessary to make the benefits of human genetics research available to indi- viduals from these groups. In the era of large human genomic initiatives, Native American populations have been neglected, in particular, the Quechua, the largest South Amerindian group settled along the Andes. We characterized the genetic diversity of a Quechua popula- tion in a global setting, using autosomal noncoding sequences (nine unlinked loci for a total of 16 kb), 351 unlinked SNPs and 678 microsatellites and tested pre- dictions of the model of the evolution of Native Ameri- cans proposed by (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 1485–1496). European admixture is <5% and African ancestry is barely detectable in the studied population. The largest genetic distances were between African versus Quechua or Melanesian popula- tions, which is concordant with the African origin of modern humans and the fact that South America was the last part of the world to be peopled. The diversity in the Quechua population is comparable with that of Eura- sian populations, and the allele frequency spectrum based on resequencing data does not reflect a reduction in the proportion of rare alleles. Thus, the Quechua population is a large reservoir of common and rare genetic variants of South Amerindians. These results are consistent with and complement our evolutionary model of South Amerindians (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 1485–1496), proposed based on Y-chromosome data, which predicts high genomic diversity due to the high level of gene flow between Andean populations and their long-term effective population size. Am J Phys Anthropol 147:443–451, 2012. V V C 2012 Wiley Periodicals, Inc. Elucidating the genetic diversity in human popula- tions is crucial to understand their evolutionary history, the genetic architecture of rare and complex diseases and ultimately, to materialize the promise of genomic medicine. For this purpose, unprecedented amounts of data are being generated in some human groups. Regret- tably, this perspective is much closer for some individu- als and populations than for other people belonging to neglected populations in human genetics research. For instance, in the last genomic revolution of human genetics (i.e., that of the Genome-Wide Association Studies), 96% of the thousands of participants in these studies are individuals of European origin (Bustamante et al., 2011). Additional Supporting Information may be found in the online version of this article. Grant sponsors: Conselho Nacional de Desenvolvimento Cientı ´fico e Tecnolo ´gico (Brazil), Fundac ¸a ˜o de Amparo a Pesquisa de Minas Gerais (Brazil), Brazilian Ministry of Education (Agency for the De- velopment of Graduate Education-CAPES) and National Cancer Institute. y These authors contributed equally to this work. *Correspondence to: Eduardo Tarazona-Santos, Departamento de Biologia Geral, Instituto de Cie ˆncias Biolo ´gicas, Universidade Fed- eral de Minas Gerais. Av. Antonio Carlos 6627, Pampulha. Caixa Postal 486, Belo Horizonte, MG, CEP 31270-910, Brazil. E-mail: edutars@icb.ufmg.br Received 11 October 2011; accepted 9 December 2011 DOI 10.1002/ajpa.22013 Published online 27 January 2012 in Wiley Online Library (wileyonlinelibrary.com). V V C 2012 WILEY PERIODICALS, INC. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 147:443–451 (2012)