RESUMEN
High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.
Asunto(s)
Genoma Humano/genética , Genómica , Migración Humana/historia , Grupos Raciales/genética , África/etnología , Animales , Asia , Conjuntos de Datos como Asunto , Estonia , Europa (Continente) , Fósiles , Flujo Génico , Genética de Población , Heterocigoto , Historia Antigua , Humanos , Nativos de Hawái y Otras Islas del Pacífico/genética , Hombre de Neandertal/genética , Nueva Guinea , Dinámica PoblacionalRESUMEN
INTRODUCTION: The steroid hormone 1,25-dihydroxyvitamin D3 is thought to protect against breast cancer. The activity of 1,25-dihydroxyvitamin D3 is mediated via the vitamin D receptor (VDR), and a number of polymorphisms in the VDR gene have been identified. These result in distinct genotypes, some of which may alter susceptibility to breast cancer. Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI) and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR. A reduced risk has been reported for the BsmI BB genotype which may influence VDR mRNA stability. AIM: We have investigated whether specific VDR gene polymorphisms are associated with breast cancer risk in Kazakhstan women. MATERIAL AND METHODS: In a case-control study, female breast cancer patients (315) and a female control group (n=604) were tested for two VDR polymorphisms. Statistical analysis was conducted using SPSS19.0. RESULTS: : The VDR rs2228570 (FokI) polymorphism was associated with an increased occurence of BC [rs2228570 (folk) ff vs. FF genotype: OR=1.71; 95% CI=1.21-2.43]. No association was noted between rs1544410 (BsmI) BB and breast cancer risk [OR=0.68; 95% CI=0.49-0.95]. CONCLUSION: : Although the factors that increase breast cancer susceptibility remain uncertain, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status. Additional testing on the effect of varying genotypes on the functional mechanisms of the VDR could help to improve future testing and treatment of woman at risk for breast cancer.