Distribution of local ancestry and evidence of adaptation in admixed populations

Secolin, Rodrigo; Mas-Sandoval, Alex; Arauna, Lara R.; Torres, Fábio R.; Araujo, Tânia Kawasaki de; Santos, Marilza L.; Rocha, Cristiane S.; Carvalho, Benilton; Cendes, Fernando; Lopes-Cendes, Íscia; Comas, David

doi:10.1038/s41598-019-50362-2

Cited by 31 publications

(54 citation statements)

References 75 publications

(138 reference statements)

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“…In summary, the maximum proportion of individuals with deleterious alleles in the population from southeastern Brazil is much lower than the one we recorded in the admixed population from northern Brazil. One possible reason for this discrepancy is the greater contribution of Amerindian ancestry to the northern (Amazonian) population in comparison with that from southeastern Brazil, since the first has an average of 30% and the second has a medium of 8.8% of Amerindian genetic background [17,18,30].…”

Section: Plos Onementioning

confidence: 99%

Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil

et al. 2020

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Introduction The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil. Methods The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa ® (Viewer of Variants) software. Results Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high

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Section: Plos Onementioning

confidence: 99%

Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil

et al. 2020

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“…Similar to other admixed American populations, the Brazilian population is derived from sub-Saharan African, European, and Native American populations 25 – 28 . However, we cannot use other admixed American populations as a reference for Brazilians due to differences in the proportions of ancestral populations from which the current Brazilian and other admixed Americans are derived 9 – 11 , 28 , 29 . In this specific case, genomic markers detected in other admixed American populations have the potential to mischaracterise the genomic landscape of interest because the allele frequencies of some genetic markers are population-specific.…”

Section: Introductionmentioning

confidence: 99%

The Brazilian Initiative on Precision Medicine (BIPMed): fostering genomic data-sharing of underrepresented populations

et al. 2020

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The development of precision medicine strategies requires prior knowledge of the genetic background of the target population. However, despite the availability of data from admixed Americans within large reference population databases, we cannot use these data as a surrogate for that of the Brazilian population. This lack of transferability is mainly due to differences between ancestry proportions of Brazilian and other admixed American populations. To address the issue, a coalition of research centres created the Brazilian Initiative on Precision Medicine (BIPMed). In this study, we aim to characterise two datasets obtained from 358 individuals from the BIPMed using two different platforms: whole-exome sequencing (WES) and a single nucleotide polymorphism (SNP) array. We estimated allele frequencies and variant pathogenicity values from the two datasets and compared our results using the BIPMed dataset with other public databases. Here, we show that the BIPMed WES dataset contains variants not included in dbSNP, including 6480 variants that have alternative allele frequencies (AAFs) >1%. Furthermore, after merging BIPMed WES and SNP array data, we identified 809,589 variants (47.5%) not present within the 1000 Genomes dataset. Our results demonstrate that, through the incorporation of Brazilian individuals into public genomic databases, BIPMed not only was able to provide valuable knowledge needed for the implementation of precision medicine but may also enhance our understanding of human genome variability and the relationship between genetic variation and disease predisposition.

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“…Similarly, a study on admixed Brazilians found PAS acting on a Native American haplotype encompassing the PPP1R3B gene, which is involved in glycogene synthesis. Such variants in Mexicans and Brazileans may have been advantageous due to increased fat and glucose storage under a restrictive diet environment ( Secolin et al. 2019 ; Ko et al 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Postadmixture Selection on Chileans Targets Haplotype Involved in Pigmentation, Thermogenesis and Immune Defense against Pathogens

Vicuña

Klimenkova

Norambuena

et al. 2020

Genome Biology and Evolution

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Abstract Detection of positive selection signatures in populations around the world is helping to uncover recent human evolutionary history as well as the genetic basis of diseases. Most human evolutionary genomic studies have been performed in European, African and Asian populations. However, populations with Native American ancestry have been largely underrepresented. Here, we used a genome-wide local ancestry enrichment approach complemented with neutral simulations to identify post-admixture adaptations underwent by admixed Chileans through gene flow from Europeans into local Native Americans. The top significant hits (P = 2.4 x 10−7) are variants in a region on chromosome 12 comprising multiple regulatory elements. This region includes rs12821256, which regulates the expression of KITLG, a well-known gene involved in lighter hair and skin pigmentation in Europeans. Another variant from that region is associated with the long noncoding RNA RP11-13A1.1, which has been specifically involved in the innate immune response against infectious pathogens (Riege, et al. 2017). Our results suggest that these genes were relevant for adaption in Chileans following the Columbian exchange.

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Distribution of local ancestry and evidence of adaptation in admixed populations

Cited by 31 publications

References 75 publications

Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil

Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil

The Brazilian Initiative on Precision Medicine (BIPMed): fostering genomic data-sharing of underrepresented populations

Postadmixture Selection on Chileans Targets Haplotype Involved in Pigmentation, Thermogenesis and Immune Defense against Pathogens

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