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- Schlebusch, Carina M., et al.
(author)
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Possible positive selection for an arsenic-protective haplotype in humans
- 2013
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:1, s. 53-58
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Journal article (peer-reviewed)abstract
- Background: Arsenic in drinking water causes severe health effects. Indigenous people in the South American Andes have likely lived with arsenic-contaminated drinking water for thousands of years. Inhabitants of San Antonio de los Cobres (SAC) in the Argentinean highlands generally carry an AS3MT (the major arsenic-metabolizing gene) haplotype associated with reduced health risks due to rapid arsenic excretion and lower urinary fraction of the monomethylated metabolite.Objectives: We hypothesized an adaptation to high-arsenic living conditions via a possible positive selection for protective AS3MT variants and compared AS3MT haplotype frequencies among different indigenous groups. Methods: Indigenous groups we evaluated were a) inhabitants of SAC and villages near Salta in northern Argentina (n = 346), b) three Native American populations from the Human Genome Diversity Project (HGDP; n = 25), and c) five Peruvian populations (n = 97). The last two groups have presumably lower historical exposure to arsenic.Results: We found a significantly higher frequency of the protective AS3MT haplotype in the SAC population (68.7%) compared with the HGDP (14.3%, p < 0.001, Fisher exact test) and Peruvian (50.5%, p < 0.001) populations. Genome-wide microsatellite (n = 671) analysis showed no detectable level of population structure between SAC and Peruvian populations (measure of population differentiation FST = 0.006) and low levels of structure between SAC and HGDP populations (FST < 0.055 for all pairs of populations compared). Conclusions: Because population stratification seems unlikely to explain the differences in AS3MT haplotype frequencies, our data raise the possibility that, during a few thousand years, natural selection for tolerance to the environmental stressor arsenic may have increased the frequency of protective variants of AS3MT. Further studies are needed to investigate this hypothesis.
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| 2. |
- Kurilshikov, Alexander, et al.
(author)
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Large-scale association analyses identify host factors influencing human gut microbiome composition
- 2021
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
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Journal article (peer-reviewed)abstract
- To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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| 3. |
- Schroeder, Kari B., et al.
(author)
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Haplotypic background of a private allele at high frequency in the Americas
- 2009
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 26:5, s. 995-1016
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Research review (peer-reviewed)abstract
- Recently, the observation of a high-frequency private allele,the 9-repeat allele at microsatellite D9S1120, in all sampledNative American and Western Beringian populations has been interpretedas evidence that all modern Native Americans descend primarilyfrom a single founding population. However, this inference assumedthat all copies of the 9-repeat allele were identical by descentand that the geographic distribution of this allele had notbeen influenced by natural selection. To investigate whetherthese assumptions are satisfied, we genotyped 34 single nucleotidepolymorphisms across 500 kilobases (kb) around D9S1120 in 21Native American and Western Beringian populations and 54 otherworldwide populations. All chromosomes with the 9-repeat alleleshare the same haplotypic background in the vicinity of D9S1120,suggesting that all sampled copies of the 9-repeat allele areidentical by descent. Ninety-one percent of these chromosomesshare the same 76.26 kb haplotype, which we call the "AmericanModal Haplotype" (AMH). Three observations lead us to concludethat the high frequency and widespread distribution of the 9-repeatallele are unlikely to be the result of positive selection:1) aside from its association with the 9-repeat allele, theAMH does not have a high frequency in the Americas, 2) the AMHis not unusually long for its frequency compared with otherhaplotypes in the Americas, and 3) in Latin American mestizopopulations, the proportion of Native American ancestry at D9S1120is not unusual compared with that observed at other genomewidemicrosatellites. Using a new method for estimating the timeto the most recent common ancestor (MRCA) of all sampled copiesof an allele on the basis of an estimate of the length of thegenealogy descended from the MRCA, we calculate the mean timeto the MRCA of the 9-repeat allele to be between 7,325 and 39,900years, depending on the demographic model used. The resultssupport the hypothesis that all modern Native Americans andWestern Beringians trace a large portion of their ancestry toa single founding population that may have been isolated fromother Asian populations prior to expanding into the Americas.
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