Dataset Information

How natural selection shapes genetic differentiation in the MHC region: A case study with Native Americans.

ABSTRACT: The Human Leukocyte Antigen (HLA) loci are extremely well documented targets of balancing selection, yet few studies have explored how selection affects population differentiation at these loci. In the present study we investigate genetic differentiation at HLA genes by comparing differentiation at microsatellites distributed genomewide to those in the MHC region. Our study uses a sample of 494 individuals from 30 human populations, 28 of which are Native Americans, all of whom were typed for genomewide and MHC region microsatellites. We find greater differentiation in the MHC than in the remainder of the genome (F_ST-MHC = 0.130 and F_ST-Genomic = 0.087), and use a permutation approach to show that this difference is statistically significant, and not accounted for by confounding factors. This finding lies in the opposite direction to the expectation that balancing selection reduces population differentiation. We interpret our findings as evidence that selection favors different sets of alleles in distinct localities, leading to increased differentiation. Thus, balancing selection at HLA genes simultaneously increases intra-population polymorphism and inter-population differentiation in Native Americans.

SUBMITTER: Nunes K

PROVIDER: S-EPMC8217218 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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How natural selection shapes genetic differentiation in the MHC region: A case study with Native Americans.

Nunes Kelly K Maia Maria Helena Thomaz MHT Dos Santos Eduardo José Melo EJM Dos Santos Sidney Emanuel Batista SEB Guerreiro João Farias JF Petzl-Erler Maria Luiza ML Bedoya Gabriel G Gallo Carla C Poletti Giovanni G Llop Elena E Tsuneto Luiza L Bortolini Maria Cátira MC Rothhammer Francisco F Single Richard R Ruiz-Linares Andrés A Rocha Jorge J Meyer Diogo D

Human immunology 20210331 7

The Human Leukocyte Antigen (HLA) loci are extremely well documented targets of balancing selection, yet few studies have explored how selection affects population differentiation at these loci. In the present study we investigate genetic differentiation at HLA genes by comparing differentiation at microsatellites distributed genomewide to those in the MHC region. Our study uses a sample of 494 individuals from 30 human populations, 28 of which are Native Americans, all of whom were typed for ge ...[more]

PMID: 33812704

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Project description:ObjectiveAlthough tribes differ with regard to the use of alcohol and drugs, substance dependence is one of the primary sources of health problems facing Native Americans. General population studies have demonstrated that substance dependence has a substantially heritable component (approximately 50% of the risk resulting from genetic influences); however, fewer studies have investigated the role of genetics in the risk for substance dependence in Native Americans.MethodThe authors present a literature review of the evidence for a genetic component in the etiology of substance dependence in Native Americans, including studies of heritability, linkage analyses, and candidate genes.ResultsEvidence for the heritability of alcohol and drug dependence was found. Linkage analyses revealed that genes influencing risk for substance dependence and related phenotypes, such as body mass index (BMI), drug tolerance, EEG patterns, and externalizing traits, reside on several chromosome regions identified in other population samples. Overlap in the gene locations for substance dependence and BMI suggests that a common genetic substrate may exist for disorders of consumption. Studies of the genes that code for alcohol-metabolizing enzymes have not revealed any risk variants specific to Native American populations, although most Native Americans lack protective variants seen in other populations. Other candidate genes associated with substance dependence phenotypes in Native Americans include OPRM1, CRN1, COMT, GABRA2, MAOA, and HTR3-B.ConclusionsSubstance dependence has a substantial genetic component in Native Americans, similar in magnitude to that reported for other populations. The high rates of substance dependence seen in some tribes is likely a combination of a lack of genetic protective factors (metabolizing enzyme variants) combined with genetically mediated risk factors (externalizing traits, consumption drive, and drug sensitivity or tolerance) that combine with key environmental factors (trauma exposure, early age at onset of use, and environmental hardship) to produce an elevated risk for the disorder.

Dataset Information

How natural selection shapes genetic differentiation in the MHC region: A case study with Native Americans.

Publications

How natural selection shapes genetic differentiation in the MHC region: A case study with Native Americans.

Similar Datasets

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