title: Genome-Wide Analysis in Brazilians Reveals Highly Differentiated Native American Genome Regions.
abstract: Despite its population, geographic size, and emerging economic importance, disproportionately little genome-scale research exists into genetic factors that predispose Brazilians to disease, or the population genetics of risk. After identification of suitable proxy populations and careful analysis of tri-continental admixture in 1,538 North-Eastern Brazilians to estimate individual ancestry and ancestral allele frequencies, we computed 400,000 genome-wide locus-specific branch length (LSBL) Fst statistics of Brazilian Amerindian ancestry compared to European and African; and a similar set of differentiation statistics for their Amerindian component compared with the closest Asian 1000 Genomes population (surprisingly, Bengalis in Bangladesh). After ranking SNPs by these statistics, we identified the top 10 highly differentiated SNPs in five genome regions in the LSBL tests of Brazilian Amerindian ancestry compared to European and African; and the top 10 SNPs in eight regions comparing their Amerindian component to the closest Asian 1000 Genomes population. We found SNPs within or proximal to the genes CIITA (rs6498115), SMC6 (rs1834619), and KLHL29 (rs2288697) were most differentiated in the Amerindian-specific branch, while SNPs in the genes ADAMTS9 (rs7631391), DOCK2 (rs77594147), SLC28A1 (rs28649017), ARHGAP5 (rs7151991), and CIITA (rs45601437) were most highly differentiated in the Asian comparison. These genes are known to influence immune function, metabolic and anthropometry traits, and embryonic development. These analyses have identified candidate genes for selection within Amerindian ancestry, and by comparison of the two analyses, those for which the differentiation may have arisen during the migration from Asia to the Americas.
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA.|Department of Public Health Sciences, University of Virginia, Charlottesville, VA.
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, Brazil.|INCT-Instituto de Biomedicina Universidade Federal do Ceará, Fortaleza, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Havt
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
authors.forename: Uma
authors.initials: U
authors.lastname: Nayak
authors.affiliation: Center for Global Health, University of Virginia, Charlottesville, VA.
authors.forename: Relana
authors.initials: R
authors.lastname: Pinkerton
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
authors.forename: Emily
authors.initials: E
authors.lastname: Farber
authors.affiliation: Genetics Institute, University of Florida, Gainesville, FL.|Department of Pathology Immunology and Laboratory Medicine, University of Florida, Gainesville, FL.
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, Brazil.|INCT-Instituto de Biomedicina Universidade Federal do Ceará, Fortaleza, Brazil.
authors.forename: Aldo A
authors.initials: AA
authors.lastname: Lima
authors.affiliation: Center for Global Health, University of Virginia, Charlottesville, VA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
mesh_terms: D000483:Alleles; D044383:Black People / Q000235:genetics; D001938:Brazil; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D007199:Indians, South American / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
keywords: Brazil.; Native American; admixture; ancestry; genetic differentiation; selection