Detecting Heterogeneity in Population Structure Across the Genome in Admixed Populations

The genetic structure of human populations is often characterized by aggregating measures of ancestry across the autosomal chromosomes. While it may be reasonable to assume that population structure patterns are similar genome-wide in relatively homogeneous populations, this assumption may not be ap...

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Vydáno v:Genetics (Austin) Ročník 204; číslo 1; s. 43 - 56
Hlavní autoři: McHugh, Caitlin, Brown, Lisa, Thornton, Timothy A
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Genetics Society of America 01.09.2016
Témata:
African Americans
African Americans - genetics
African Continental Ancestry Group - genetics
Chromosomes
Chromosomes, Human, X
Equilibrium
Ethnic Groups - genetics
European Continental Ancestry Group - genetics
Female
Gene Frequency
Genealogy
Genes
Genetic Heterogeneity
Genetic structure
Genetics, Population - methods
Genome, Human
Genome-Wide Association Study - methods
Genomes
Genomics
HapMap Project
Heterogeneity
Hispanic Americans
Hispanic Americans - genetics
Human populations
Humans
Indigenous peoples
Investigations
Male
Methods
Polymorphism, Single Nucleotide
Population structure
Studies
Variance analysis
admixture
population structure
assortative mating
local ancestry
heterogeneity testing
ISSN:1943-2631, 0016-6731, 1943-2631
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Shrnutí:The genetic structure of human populations is often characterized by aggregating measures of ancestry across the autosomal chromosomes. While it may be reasonable to assume that population structure patterns are similar genome-wide in relatively homogeneous populations, this assumption may not be appropriate for admixed populations, such as Hispanics and African-Americans, with recent ancestry from two or more continents. Recent studies have suggested that systematic ancestry differences can arise at genomic locations in admixed populations as a result of selection and nonrandom mating. Here, we propose a method, which we refer to as the chromosomal ancestry differences (CAnD) test, for detecting heterogeneity in population structure across the genome. CAnD can incorporate either local or chromosome-wide ancestry inferred from SNP genotype data to identify chromosomes harboring genomic regions with ancestry contributions that are significantly different than expected. In simulation studies with real genotype data from phase III of the HapMap Project, we demonstrate the validity and power of CAnD. We apply CAnD to the HapMap Mexican-American (MXL) and African-American (ASW) population samples; in this analysis the software RFMix is used to infer local ancestry at genomic regions, assuming admixing from Europeans, West Africans, and Native Americans. The CAnD test provides strong evidence of heterogeneity in population structure across the genome in the MXL sample (p=1e−5), which is largely driven by elevated Native American ancestry and deficit of European ancestry on the X chromosomes. Among the ASW, all chromosomes are largely African derived and no heterogeneity in population structure is detected in this sample.
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ISSN:1943-2631
0016-6731
1943-2631
DOI:10.1534/genetics.115.184184