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Amerindian-specific regions under positive selection harbour new lipid variants in Latinos.

ABSTRACT: Dyslipidemia and obesity are especially prevalent in populations with Amerindian backgrounds, such as Mexican-Americans, which predispose these populations to cardiovascular disease. Here we design an approach, known as the cross-population allele screen (CPAS), which we conduct prior to a genome-wide association study (GWAS) in 19,273 Europeans and Mexicans, in order to identify Amerindian risk genes in Mexicans. Utilizing CPAS to restrict the GWAS input variants to only those differing in frequency between the two populations, we identify novel Amerindian lipid genes, receptor-related orphan receptor alpha (RORA) and salt-inducible kinase 3 (SIK3), and three loci previously unassociated with dyslipidemia or obesity. We also detect lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5) harbouring specific Amerindian signatures of risk variants and haplotypes. Notably, we observe that SIK3 and one novel lipid locus underwent positive selection in Mexicans. Furthermore, after a high-fat meal, the SIK3 risk variant carriers display high triglyceride levels. These findings suggest that Amerindian-specific genetic architecture leads to a higher incidence of dyslipidemia and obesity in modern Mexicans.

SUBMITTER: Ko A

PROVIDER: S-EPMC4062071 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Amerindian-specific regions under positive selection harbour new lipid variants in Latinos.

Ko Arthur A Cantor Rita M RM Weissglas-Volkov Daphna D Nikkola Elina E Reddy Prasad M V Linga PM Sinsheimer Janet S JS Pasaniuc Bogdan B Brown Robert R Alvarez Marcus M Rodriguez Alejandra A Rodriguez-Guillen Rosario R Bautista Ivette C IC Arellano-Campos Olimpia O Muñoz-Hernández Linda L LL Salomaa Veikko V Kaprio Jaakko J Jula Antti A Jauhiainen Matti M Heliövaara Markku M Raitakari Olli O Lehtimäki Terho T Eriksson Johan G JG Perola Markus M Lohmueller Kirk E KE Matikainen Niina N Taskinen Marja-Riitta MR Rodriguez-Torres Maribel M Riba Laura L Tusie-Luna Teresa T Aguilar-Salinas Carlos A CA Pajukanta Päivi P

Nature communications 20140602

Dyslipidemia and obesity are especially prevalent in populations with Amerindian backgrounds, such as Mexican-Americans, which predispose these populations to cardiovascular disease. Here we design an approach, known as the cross-population allele screen (CPAS), which we conduct prior to a genome-wide association study (GWAS) in 19,273 Europeans and Mexicans, in order to identify Amerindian risk genes in Mexicans. Utilizing CPAS to restrict the GWAS input variants to only those differing in freq ...[more]

PMID: 24886709

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Project description:Meat and egg-type chickens have been selected for several generations for different traits. Artificial and natural selection for different phenotypes can change frequency of genetic variants, leaving particular genomic footprints throghtout the genome. Thus, the aims of this study were to sequence 28 chickens from two Brazilian lines (meat and white egg-type) and use this information to characterize genome-wide genetic variations, identify putative regions under selection using Fst method, and find putative pathways under selection.A total of 13.93 million SNPs and 1.36 million INDELs were identified, with more variants detected from the broiler (meat-type) line. Although most were located in non-coding regions, we identified 7255 intolerant non-synonymous SNPs, 512 stopgain/loss SNPs, 1381 frameshift and 1094 non-frameshift INDELs that may alter protein functions. Genes harboring intolerant non-synonymous SNPs affected metabolic pathways related mainly to reproduction and endocrine systems in the white-egg layer line, and lipid metabolism and metabolic diseases in the broiler line. Fst analysis in sliding windows, using SNPs and INDELs separately, identified over 300 putative regions of selection overlapping with more than 250 genes. For the first time in chicken, INDEL variants were considered for selection signature analysis, showing high level of correlation in results between SNP and INDEL data. The putative regions of selection signatures revealed interesting candidate genes and pathways related to important phenotypic traits in chicken, such as lipid metabolism, growth, reproduction, and cardiac development.In this study, Fst method was applied to identify high confidence putative regions under selection, providing novel insights into selection footprints that can help elucidate the functional mechanisms underlying different phenotypic traits relevant to meat and egg-type chicken lines. In addition, we generated a large catalog of line-specific and common genetic variants from a Brazilian broiler and a white egg layer line that can be used for genomic studies involving association analysis with phenotypes of economic interest to the poultry industry.

Dataset Information

Amerindian-specific regions under positive selection harbour new lipid variants in Latinos.

Publications

Amerindian-specific regions under positive selection harbour new lipid variants in Latinos.

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