A minimum set of ancestry informative markers for determining admixture proportions in a mixed American population: the Brazilian set

Barreto, Mauricio Lima “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-07T12:22:48Z No. of bitstreams: 1 Santos HC A minimum set....pdf: 1062773 bytes, checksum: 9434fea963814081a138b951934c70aa (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-07T13:32:45Z (GMT) No. of bitstreams: 1 Santos HC A minimum set....pdf: 1062773 bytes, checksum: 9434fea963814081a138b951934c70aa (MD5)Made available in DSpace on 2017-08-07T13:32:45Z (GMT). No. of bitstreams: 1 Santos HC A minimum set....pdf: 1062773 bytes, checksum: 9434fea963814081a138b951934c70aa (MD5) Previous issue date: 2016Department of Science and Technology (DECIT/ SCTIE) and National Fund for Scientific and Technological Development (FNDCT), Ministry of Health, Brazil; Funding of Studies and Projects (FINEP), Ministry of Science and Technology, Brazil; Coordination of Improvement of Higher Education Personnel (CAPES), Ministry of Education, Brazil. HCS is supported by a grant from the São Paulo Research Foundation (FAPESP).Medical School of University of São Paulo. Heart Institute. Laboratory of Genetics and Molecular Cardiology. São Paulo, SP, BrazilMedical School of University of São Paulo. Heart Institute. Laboratory of Genetics and Molecular Cardiology. São Paulo, SP, BrazilFederal University of Minas Gerais. General Biology Department. Belo Horizonte, MG, BrazilFederal University of Minas Gerais. General Biology Department. Belo Horizonte, MG, BrazilFederal University of Bahia. Institute of Public Health. Salvador, BA, BrazilFederal University of Pelotas. Porto Alegre, RGS, BrazilOswaldo Cruz Foundation. Rene Rachou Research Institute. Belo Horizonte, MG, BrazilFederal University of Minas Gerais. General Biology Department. Belo Horizonte, MG, BrazilFederal University of Minas Gerais. General Biology Department. Belo Horizonte, MG, BrazilFederal University of Bahia. Institute of Public Health. Salvador, BA, BrazilMedical School of University of São Paulo. Heart Institute. Laboratory of Genetics and Molecular Cardiology. São Paulo, SP, BrazilMedical School of University of São Paulo. Heart Institute. Laboratory of Genetics and Molecular Cardiology. São Paulo, SP, BrazilFederal University of Minas Gerais. General Biology Department. Belo Horizonte, MG, BrazilFederal University of Minas Gerais. General Biology Department. Belo Horizonte, MG, BrazilFederal University of Minas Gerais. General Biology Department. Belo Horizonte, MG, BrazilMedical School of University of São Paulo. Heart Institute. Laboratory of Genetics and Molecular Cardiology. São Paulo, SP, BrazilThe Brazilian EPIGEN Project ConsortiumThe Brazilian population is considered to be highly admixed. The main contributing ancestral populations were European and African, with Amerindians contributing to a lesser extent. The aims of this study were to provide a resource for determining and quantifying individual continental ancestry using the smallest number of SNPs possible, thus allowing for a cost- and time-efficient strategy for genomic ancestry determination. We identified and validated a minimum set of 192 ancestry informative markers (AIMs) for the genetic ancestry determination of Brazilian populations. These markers were selected on the basis of their distribution throughout the human genome, and their capacity of being genotyped on widely available commercial platforms. We analyzed genotyping data from 6487 individuals belonging to three Brazilian cohorts. Estimates of individual admixture using this 192 AIM panels were highly correlated with estimates using ~370 000 genome-wide SNPs: 91%, 92%, and 74% of, respectively, African, European, and Native American ancestry components. Besides that, 192 AIMs are well distributed among populations from these ancestral continents, allowing greater freedom in future studies with this panel regarding the choice of reference populations. We also observed that genetic ancestry inferred by AIMs provides similar association results to the one obtained using ancestry inferred by genomic data (370 K SNPs) in a simple regression model with rs1426654, related to skin pigmentation, genotypes as dependent variable. In conclusion, these markers can be used to identify and accurately quantify ancestry of Latin Americans or US Hispanics/Latino individuals, in particular in the context of fine-mapping strategies that require the quantification of continental ancestry in thousands of individuals

Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations.

While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes