Copyright © 2007 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 80, Issue 6, 1024-1036, 1 June 2007
doi:10.1086/518313
Article
Alkes L. Pricea, b, Nick Pattersonb, Fuli Yua, b, David R. Coxc, Alicja Waliszewskaa, b, Gavin J. McDonalda, b, Arti Tandona, b, Christine Schirmera, b, Julie Neubauera, b, Gabriel Bedoya, Constanza Duque, Alberto Villegas, Maria Catira Bortolinie, Francisco M. Salzanoe, Carla Gallof, Guido Mazzottif, Marcela Tello-Ruiz, Laura Riba, Carlos A. Aguilar-Salinas, Samuel Canizales-Quinteros, Marta Menjivari, William Klitzk, l, Brian Hendersonm, Christopher A. Haimanm, Cheryl Winklern, Teresa Tusie-Luna, Andrés Ruiz-Linares and David Reicha, b,
, 
a Department of Genetics, Harvard Medical School, Boston
b Medical and Population Genetics Group, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA
c Perlegen Sciences, Mountain View, CA
d Laboratorio de Genética Molecular, Universidad de Antioquia, Medellín, Colombia
e Departamento de Genetica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
f Laboratorios de Investigación y Desarrollo, Falcultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima
g Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
h Unit of Molecular Biology and Genomic Medicine, Instituto de Investigaciones Biomedicas
i Biology Department, Facultad de Química
j Universidad Nacional Autónoma de México, and Departament de Endocrinology y Metabolism, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
k Mexico City; School of Public Health, University of California, Berkeley
l Public Health Institute, Oakland
m Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles
n Laboratory of Genomic Diversity, SAIC-Frederick, National Cancer Institute, Frederick, MD
o and The Galton Laboratory, Department of Biology, University College London, London
Address for correspondence and reprints: Dr. David Reich, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115.Abstract
Admixture mapping is an economical and powerful approach for localizing disease genes in populations of recently mixed ancestry and has proven successful in African Americans. The method holds equal promise for Latinos, who typically inherit a mix of European, Native American, and African ancestry. However, admixture mapping in Latinos has not been practical because of the lack of a map of ancestry-informative markers validated in Native American and other populations. To address this, we screened multiple databases, containing millions of markers, to identify 4,186 markers that were putatively informative for determining the ancestry of chromosomal segments in Latino populations. We experimentally validated each of these markers in at least 232 new Latino, European, Native American, and African samples, and we selected a subset of 1,649 markers to form an admixture map. An advantage of our strategy is that we focused our map on markers distinguishing Native American from other ancestries and restricted it to markers with very similar frequencies in Europeans and Africans, which decreased the number of markers needed and minimized the possibility of false disease associations. We evaluated the effectiveness of our map for localizing disease genes in four Latino populations from both North and South America.
| Mitochondrial Population Genomics Supports a Single Pre-Clovis Origin with a Coastal Route for the Peopling of the Americas The American Journal of Human Genetics, Volume 82, Issue 3, 3 March 2008, Pages 583-592 Nelson J.R. Fagundes, Ricardo Kanitz, Roberta Eckert, Ana C.S. Valls, Mauricio R. Bogo, Francisco M. Salzano, David Glenn Smith, Wilson A. Silva, Marco A. Zago, Andrea K. Ribeiro-dos-Santos, Sidney E.B. Santos, Maria Luiza Petzl-Erler and Sandro L. Bonatto Abstract It is well accepted that the Americas were the last continents reached by modern humans, most likely through Beringia. However, the precise time and mode of the colonization of the New World remain hotly disputed issues. Native American populations exhibit almost exclusively five mitochondrial DNA (mtDNA) haplogroups (A–D and X). Haplogroups A–D are also frequent in Asia, suggesting a northeastern Asian origin of these lineages. However, the differential pattern of distribution and frequency of haplogroup X led some to suggest that it may represent an independent migration to the Americas. Here we show, by using 86 complete mitochondrial genomes, that all Native American haplogroups, including haplogroup X, were part of a single founding population, thereby refuting multiple-migration models. A detailed demographic history of the mtDNA sequences estimated with a Bayesian coalescent method indicates a complex model for the peopling of the Americas, in which the initial differentiation from Asian populations ended with a moderate bottleneck in Beringia during the last glacial maximum (LGM), around ∼23,000 to ∼19,000 years ago. Toward the end of the LGM, a strong population expansion started ∼18,000 and finished ∼15,000 years ago. These results support a pre-Clovis occupation of the New World, suggesting a rapid settlement of the continent along a Pacific coastal route. Abstract | | |
| Reconstructing Genetic Ancestry Blocks in Admixed Individuals The American Journal of Human Genetics, Volume 79, Issue 1, 1 July 2006, Pages 1-12 Hua Tang, Marc Coram, Pei Wang, Xiaofeng Zhu and Neil Risch Abstract A chromosome in an individual of recently admixed ancestry resembles a mosaic of chromosomal segments, or ancestry blocks, each derived from a particular ancestral population. We consider the problem of inferring ancestry along the chromosomes in an admixed individual and thereby delineating the ancestry blocks. Using a simple population model, we infer gene-flow history in each individual. Compared with existing methods, which are based on a hidden Markov model, the Markov–hidden Markov model (MHMM) we propose has the advantage of accounting for the background linkage disequilibrium (LD) that exists in ancestral populations. When there are more than two ancestral groups, we allow each ancestral population to admix at a different time in history. We use simulations to illustrate the accuracy of the inferred ancestry as well as the importance of modeling the background LD; not accounting for background LD between markers may mislead us to false inferences about mixed ancestry in an indigenous population. The MHMM makes it possible to identify genomic blocks of a particular ancestry by use of any high-density single-nucleotide–polymorphism panel. One application of our method is to perform admixture mapping without genotyping special ancestry-informative–marker panels. Abstract | | |
| Genetic Differentiation in South Amerindians Is Related to Environmental and Cultural Diversity: Evidence from the Y Chromosome The American Journal of Human Genetics, Volume 68, Issue 6, 1 June 2001, Pages 1485-1496 Eduardo Tarazona-Santos, Denise R. Carvalho-Silva, Davide Pettener, Donata Luiselli, Gian Franco De Stefano, Cristina Martinez Labarga, Olga Rickards, Chris Tyler-Smith, Sérgio D.J. Pena and Fabrício R. Santos Abstract The geographic structure of Y-chromosome variability has been analyzed in native populations of South America, through use of the high-frequency Native American haplogroup defined by the DYS199-T allele and six Y-chromosome–linked microsatellites (DYS19, DYS389A, DYS389B, DYS390, DYS391, and DYS393), analyzed in 236 individuals. The following pattern of within- and among-population variability emerges from the analysis of microsatellite data: (1) the Andean populations exhibit significantly higher levels of within-population variability than do the eastern populations of South America; (2) the spatial-autocorrelation analysis suggests a significant geographic structure of Y-chromosome genetic variability in South America, although a typical evolutionary pattern could not be categorically identified; and (3) genetic-distance analyses and the analysis of molecular variance suggest greater homogeneity between Andean populations than between non-Andean ones. On the basis of these results, we propose a model for the evolution of the male lineages of South Amerindians that involves differential patterns of genetic drift and gene flow. In the western part of the continent, which is associated with the Andean area, populations have relatively large effective sizes and gene-flow levels among them, which has created a trend toward homogenization of the gene pool. On the other hand, eastern populations—settled in the Amazonian region, the central Brazilian plateau, and the Chaco region—have exhibited higher rates of genetic drift and lower levels of gene flow, with a resulting trend toward genetic differentiation. This model is consistent with the linguistic and cultural diversity of South Amerindians, the environmental heterogeneity of the continent, and the available paleoecological data. Abstract | | |