Genotype, haplotype and copy-number variation in worldwide human populations

Abstract

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups. Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms (SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected--including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas--the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.

Application of principal component analysis to pharmacogenomic studies in Canada

“…25,26 In this study, visual inspection of plots of subsequent components (PC3-PC10) did not show further discrimination possible between subpopulations (data not shown).…”

“…As expected, the cluster pattern resembled a geographic map of the world with the three continents Europe, Asia and Africa each on different points of the 'triangle', consistent with other reports. 25,26 The first PC distinguished between Europeans and East-Asians, with samples from the Indian subcontinent at intermediate values.…”

Implications of gene copy-number variation in health and diseases

“…In past few years, we have learned a lot about the CNVs and their implication on our health and diseases. Observation from the comprehensive maps generated by Redon et al 6 and Jakobsson et al 69 have established CNVs as one of the prominent genetic variation having an important role in interindividual and inter-ethnic differences in susceptibility to common and complex diseases. 70 Still more technical advances are awaited for large-scale survey of CNVs, INDELs and other variants in many racial and ethnic populations.…”

Extensive genome-wide autozygosity in the population isolates of Daghestan

“…To control for the effect of sample size differences on r 2 , we randomly re-sampled 11 individuals when computing r 2 for each SNP pair. 55 All SNPs were assigned to genetic map positions using the CEU or YRI HapMap (hg18) recombination maps. r 2 values were binned into 50 genetic distance groups between 0.005 and 0.25 cM in increments of 0.005 cM, and their mean r 2 was used for further calculation of effective population size (N e ).…”