Geographic Patterns of Genome Admixture in Latin American Mestizos
University College London1, University of Bern2, University of Antioquia3, Cayetano Heredia University4, University of New Mexico5, Universidad Autónoma de la Ciudad de México6, University of California, Berkeley7, University of Costa Rica8, University of California, Los Angeles9, Universidade Federal do Rio Grande do Sul10, Federal University of Paraná11, National University of Jujuy12, University of Chile13, University of Tarapacá14
TL;DR: An analysis of admixture in thirteen Mestizo populations from seven countries in Latin America based on data for 678 autosomal and 29 X-chromosome microsatellites found extensive variation in Native American and European ancestry among populations and individuals and evidence that admixture across Latin America has often involved predominantly European men and both Native and African women.
Abstract: The large and diverse population of Latin America is potentially a powerful resource for elucidating the genetic basis of complex traits through admixture mapping. However, no genome-wide characterization of admixture across Latin America has yet been attempted. Here, we report an analysis of admixture in thirteen Mestizo populations (i.e. in regions of mainly European and Native settlement) from seven countries in Latin America based on data for 678 autosomal and 29 X-chromosome microsatellites. We found extensive variation in Native American and European ancestry (and generally low levels of African ancestry) among populations and individuals, and evidence that admixture across Latin America has often involved predominantly European men and both Native and African women. An admixture analysis allowing for Native American population subdivision revealed a differentiation of the Native American ancestry amongst Mestizos. This observation is consistent with the genetic structure of pre-Columbian populations and with admixture having involved Natives from the area where the Mestizo examined are located. Our findings agree with available information on the demographic history of Latin America and have a number of implications for the design of association studies in population from the region.
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Massachusetts Institute of Technology1, Harvard University2, University of Hong Kong3, University College London4, Aix-Marseille University5, University of Geneva6, University of Antioquia7, National Scientific and Technical Research Council8, University of Buenos Aires9, Universidade Federal do Rio Grande do Sul10, Federal University of Paraná11, National Autonomous University of Mexico12, Mexican Social Security Institute13, Instituto Politécnico Nacional14, Nestlé15, Universidad Autónoma de Nuevo León16, University of Santiago de Compostela17, Cayetano Heredia University18, University of Chicago19, Russian Academy of Sciences20, Université de Montréal21, University of Costa Rica22, Swiss Institute of Bioinformatics23, University of Bern24, University of Tarapacá25, Paul Sabatier University26, University of California, Berkeley27, Yale University28, Semel Institute for Neuroscience and Human Behavior29
TL;DR: It is shown that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America.
Abstract: The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.
696 citations
TL;DR: Investigation of a greater diversity of populations could make substantial contributions to the goal of mapping the genetic determinants of complex diseases for the human population as a whole.
Abstract: Genome-wide association (GWA) studies have identified a large number of SNPs associated with disease phenotypes. As most GWA studies have been performed in populations of European descent, this Review examines the issues involved in extending the consideration of GWA studies to diverse worldwide populations. Although challenges exist with issues such as imputation, admixture and replication, investigation of a greater diversity of populations could make substantial contributions to the goal of mapping the genetic determinants of complex diseases for the human population as a whole.
573 citations
Cites background from "Geographic Patterns of Genome Admix..."
...Admixed populations often have high variation across individuals in the proportions of ancestry from the various source group...
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TL;DR: The authors studied the genetic ancestry of 5,269 self-described African Americans, 8,663 Latinos, and 148,789 European Americans who are 23andMe customers and showed that the legacy of these historical interactions is visible in the genetic lineage of present-day Americans.
Abstract: Over the past 500 years, North America has been the site of ongoing mixing of Native Americans, European settlers, and Africans (brought largely by the trans-Atlantic slave trade), shaping the early history of what became the United States. We studied the genetic ancestry of 5,269 self-described African Americans, 8,663 Latinos, and 148,789 European Americans who are 23andMe customers and show that the legacy of these historical interactions is visible in the genetic ancestry of present-day Americans. We document pervasive mixed ancestry and asymmetrical male and female ancestry contributions in all groups studied. We show that regional ancestry differences reflect historical events, such as early Spanish colonization, waves of immigration from many regions of Europe, and forced relocation of Native Americans within the US. This study sheds light on the fine-scale differences in ancestry within and across the United States and informs our understanding of the relationship between racial and ethnic identities and genetic ancestry.
484 citations
Harvard University1, Beth Israel Deaconess Medical Center2, Centro de Investigación y Docencia Económicas3, Pontifícia Universidade Católica do Rio Grande do Sul4, Universidade Federal do Rio Grande do Sul5, University of the Republic6, Union for International Cancer Control7, National Autonomous University of Mexico8, King's College London9, Pan American Health Organization10, Federal University of São Paulo11, University of Virginia12, University of Chicago13, Massachusetts Institute of Technology14, Johns Hopkins University15, Johns Hopkins University School of Medicine16, East Jefferson General Hospital17, Hoffmann-La Roche18, PATH19, University of Milan20, Hospital Maciel21, St. Jude Children's Research Hospital22, University of Tennessee Health Science Center23, International Atomic Energy Agency24, University of Buenos Aires25, University of São Paulo26, Universidad de La Sabana27, University of Texas MD Anderson Cancer Center28, University of Houston29, GlaxoSmithKline30, American Cancer Society31
TL;DR: In this article, the authors present the findings of their Cancer Commission and their recommendations to encourage Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.
Abstract: Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.
418 citations
TL;DR: Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country, and two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function.
Abstract: Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide.
416 citations
References
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TL;DR: Pritch et al. as discussed by the authors proposed a model-based clustering method for using multilocus genotype data to infer population structure and assign individuals to populations, which can be applied to most of the commonly used genetic markers, provided that they are not closely linked.
Abstract: We describe a model-based clustering method for using multilocus genotype data to infer population structure and assign individuals to populations. We assume a model in which there are K populations (where K may be unknown), each of which is characterized by a set of allele frequencies at each locus. Individuals in the sample are assigned (probabilistically) to populations, or jointly to two or more populations if their genotypes indicate that they are admixed. Our model does not assume a particular mutation process, and it can be applied to most of the commonly used genetic markers, provided that they are not closely linked. Applications of our method include demonstrating the presence of population structure, assigning individuals to populations, studying hybrid zones, and identifying migrants and admixed individuals. We show that the method can produce highly accurate assignments using modest numbers of loci— e.g. , seven microsatellite loci in an example using genotype data from an endangered bird species. The software used for this article is available from http://www.stats.ox.ac.uk/~pritch/home.html.
27,454 citations
TL;DR: Extensions to the method of Pritchard et al. for inferring population structure from multilocus genotype data are described and methods that allow for linkage between loci are developed, which allows identification of subtle population subdivisions that were not detectable using the existing method.
Abstract: We describe extensions to the method of Pritchard et al. for inferring population structure from multilocus genotype data. Most importantly, we develop methods that allow for linkage between loci. The new model accounts for the correlations between linked loci that arise in admixed populations (“admixture linkage disequilibium”). This modification has several advantages, allowing (1) detection of admixture events farther back into the past, (2) inference of the population of origin of chromosomal regions, and (3) more accurate estimates of statistical uncertainty when linked loci are used. It is also of potential use for admixture mapping. In addition, we describe a new prior model for the allele frequencies within each population, which allows identification of subtle population subdivisions that were not detectable using the existing method. We present results applying the new methods to study admixture in African-Americans, recombination in Helicobacter pylori , and drift in populations of Drosophila melanogaster . The methods are implemented in a program, structure , version 2.0, which is available at http://pritch.bsd.uchicago.edu.
7,615 citations
Council on Education for Public Health1, Cancer Research UK2, French Institute of Health and Medical Research3, Peking Union Medical College4, Chinese Academy of Sciences5, University of Geneva6, National Cancer Research Institute7, Temple University8, University of Los Andes9, Florida International University10, Harbin Medical University11, Yale University12, Stanford University13, University of Turin14, Marshfield Clinic15
TL;DR: A resource of 1064 cultured lymphoblastoid cell lines from individuals in different world populations and corresponding milligram quantities of DNA is deposited at the Foundation Jean Dausset (CEPH) in Paris.
Abstract: A resource of 1064 cultured lymphoblastoid cell lines (LCLs) ([1][1]) from individuals in different world populations and corresponding milligram quantities of DNA is deposited at the Foundation Jean Dausset (CEPH) ([2][2]) in Paris. LCLs were collected from various laboratories by the Human Genome
1,002 citations
"Geographic Patterns of Genome Admix..." refers methods in this paper
...Unfortunately, although it is broadly known that the history of Latin America entailed an extensive admixture of Native PLoS Genetics | www.plosgenetics.org 1 2008 | Volume 4 | Issue 3 | e1000037 Americans, Europeans and Africans, few details are known about this process or about its genetic correlates[16–19]....
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...The expected heterozygosity (I) for the Mestizo was calculated using the expression of Rosenberg and Huang (personal communication): I~c2IAz(1{c) 2IBzc(1{c)(IAzIB) 1zF 1{F Where IA and IB are the observed heterozygosities of European and Native American populations, F the FST estimated between Europeans and Africans, and c the proportion of European ancestry in the Mestizo....
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...Most analyses were carried out using a dataset that also included genotype information for 160 Europeans, 123 Africans and 463 Native Americans (from 26 Amerindian populations, samples size 7–25)....
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...K was varied in order to examine different groupings of Native American populations while considering Europeans and Africans as single independent clusters: K = 3 when grouping all Native American data into a single cluster, K = 7 when Native American populations were grouped into five linguistic stocks and K = 28 when each Native American population was considered independently....
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...We analyzed genotype data for 678 autosomal and 29 Xchromosome microsatellites collected in the Mestizo populations together with similar data available in samples from Europeans, Native Americans and Africans[22,23]....
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TL;DR: Significant nonrandom association between two markers located 22 cM apart (FY-null and AT3) is detected, most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations, emphasize the importance of admixed populations as a useful resource for mapping traits with different prevalence in two parental population.
Abstract: We analyzed the European genetic contribution to 10 populations of African descent in the United States (Maywood, Illinois; Detroit; New York; Philadelphia; Pittsburgh; Baltimore; Charleston, South Carolina; New Orleans; and Houston) and in Jamaica, using nine autosomal DNA markers. These markers either are population-specific or show frequency differences >45% between the parental populations and are thus especially informative for admixture. European genetic ancestry ranged from 6.8% (Jamaica) to 22.5% (New Orleans). The unique utility of these markers is reflected in the low variance associated with these admixture estimates (SEM 1.3%-2.7%). We also estimated the male and female European contribution to African Americans, on the basis of informative mtDNA (haplogroups H and L) and Y Alu polymorphic markers. Results indicate a sex-biased gene flow from Europeans, the male contribution being substantially greater than the female contribution. mtDNA haplogroups analysis shows no evidence of a significant maternal Amerindian contribution to any of the 10 populations. We detected significant nonrandom association between two markers located 22 cM apart (FY-null and AT3), most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations. The strength of this association and the substantial genetic distance between FY and AT3 emphasize the importance of admixed populations as a useful resource for mapping traits with different prevalence in two parental populations.
769 citations
"Geographic Patterns of Genome Admix..." refers background in this paper
...Such a sex bias in African admixture has been inferred African Americans from the US[39] but had not been evidenced in Mestizos....
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