Whole genome variation in 27 Mexican indigenous populations, demographic and biomedical insights
Por:
Aguilar-Ordonez, Israel, Perez-Villatoro, Fernando, Garcia-Ortiz, Humberto, Barajas-Olmos, Francisco, Ballesteros-Villascan, Judith, Gonzalez-Buenfil, Ram, Fresno, Cristobal, Garciarrubio, Alejandro, Carlos Fernandez-Lopez, Juan, Tovar, Hugo, Hernandez-Lemus, Enrique, Orozco, Lorena, Soberon, Xavier, Morett, Enrique
Publicada:
8 abr 2021
Categoría:
Multidisciplinary
Resumen:
There has been limited study of Native American whole genome diversity
to date, which impairs effective implementation of personalized medicine
and a detailed description of its demographic history. Here we report
high coverage whole genome sequencing of 76 unrelated individuals, from
27 indigenous groups across Mexico, with more than 97% average Native
American ancestry. On average, each individual has 3.26 million Single
Nucleotide Variants and short indels, that together comprise a catalog
of 9,737,152 variants, 44,118 of which are novel. We report 497 common
Single Nucleotide Variants (with allele frequency > 5%) mapped to drug
responses and 316,577 in enhancer or promoter elements; interestingly we
found some of these enhancer variants in PPARG, a nuclear receptor
involved in highly prevalent health problems in Mexican population, such
as obesity, diabetes, and insulin resistance. By detecting signals of
positive selection we report 24 enriched key pathways under selection,
most of them related to immune mechanisms. No missense variants in ACE2,
the receptor responsible for the entry of the SARS CoV-2 virus, were
found in any individual. Population genomics and phylogenetic analyses
demonstrated stratification in a Northern-Central-Southern axis, with
major substructure in the Central region. The Seri, a northern group
with the most genetic divergence in our study, showed a distinctive
genomic context with the most novel variants, and the most population
specific genotypes. Genome-wide analysis showed that the average
haplotype blocks are longer in Native Mexicans than in other world
populations. With this dataset we describe previously undetected
population level variation in Native Mexicans, helping to reduce the gap
in genomic data representation of such groups.
Filiaciones:
Aguilar-Ordonez, Israel:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca, Morelos, Mexico
Inst Nacl Med Genom INMEGEN, Mexico City, DF, Mexico
Perez-Villatoro, Fernando:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca, Morelos, Mexico
Inst Nacl Med Genom INMEGEN, Mexico City, DF, Mexico
Winter Genom, Mexico City, DF, Mexico
Garcia-Ortiz, Humberto:
Inst Nacl Med Genom INMEGEN, Mexico City, DF, Mexico
Barajas-Olmos, Francisco:
Inst Nacl Med Genom INMEGEN, Mexico City, DF, Mexico
Ballesteros-Villascan, Judith:
Benemerita Univ Autonoma Puebla BUAP, Puebla, Mexico
Gonzalez-Buenfil, Ram:
Benemerita Univ Autonoma Puebla BUAP, Puebla, Mexico
Fresno, Cristobal:
Inst Nacl Med Genom INMEGEN, Mexico City, DF, Mexico
Garciarrubio, Alejandro:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca, Morelos, Mexico
Carlos Fernandez-Lopez, Juan:
Inst Nacl Med Genom INMEGEN, Mexico City, DF, Mexico
Tovar, Hugo:
Inst Nacl Med Genom INMEGEN, Mexico City, DF, Mexico
Hernandez-Lemus, Enrique:
Inst Nacl Med Genom INMEGEN, Mexico City, DF, Mexico
Orozco, Lorena:
Inst Nacl Med Genom INMEGEN, Mexico City, DF, Mexico
Soberon, Xavier:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca, Morelos, Mexico
Inst Nacl Med Genom INMEGEN, Mexico City, DF, Mexico
Morett, Enrique:
Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca, Morelos, Mexico
Gold, Green Published
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