Genetic Variation and Recent Positive Selection in Worldwide Human Populations: Evidence from Nearly 1 Million SNPs

Abstract

BackgroundGenome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs) have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world.MethodologyWe genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations) from the Human Genome Diversity Panel (HGDP-CEPH). When merged with non-overlapping SNPs typed previously in 250 of these same individuals, the resulting data consist of over 950,000 SNPs. We then analyzed the genetic relationships and ancestry of individuals without assigning them to populations, and we also identified candidate regions of recent positive selection at both the population and regional (continental) level.ConclusionsOur analyses both confirm and extend previous studies; in particular, we highlight the impact of various dispersals, and the role of substructure in Africa, on human genetic diversity. We also identified several novel candidate regions for recent positive selection, and a gene ontology (GO) analysis identified several GO groups that were significantly enriched for such candidate genes, including immunity and defense related genes, sensory perception genes, membrane proteins, signal receptors, lipid binding/metabolism genes, and genes involved in the nervous system. Among the novel candidate genes identified are two genes involved in the thyroid hormone pathway that show signals of selection in African Pygmies that may be related to their short stature.

Genome-wide genetic diversity, population structure and admixture analysis in African and Asian cattle breeds

“…The population structure and phylogenic trees analyses performed here clearly showed the largest divergence between B. taurus (Hanwoo) and B. indicus (Asian zebu), which is consistent with previous studies and supports independent domestication of the two bovine species (Loftus et al, 1994;Gautier et al, 2010;Decker et al, 2014). Previous SNP-based studies in cattle, sheep and humans demonstrated that PC1 and PC2 primarily clustered breeds or populations according to their geographic origin (Herráez et al, 2009;Gauiter et al, 2010;Kijas et al, 2012). Similarly, our PCA analysis separated individual animals according to their geographic origin and domestication history.…”

“…Ascertainment biases can be minimized by LD-pruning of closely associated SNPs and by analyzing haplotypes instead of individual SNPs (Herráez et al, 2009). We used different SNP data sets to assess the effects of ascertainment biases on population diversity indexes and differentiation.…”

“…Exclusion of markers in high linkage disequilibrium (LD) has been shown to minimize the effects of these biases (Herráez et al, 2009;Kijas et al, 2012). To assess the effects of ascertainment bias on diversity indexes and genetic distances we used three SNP data sets: (a) 54 404 autosomal SNPs that remained after applying filtering criteria (call rate >98%, MAF >5% and Hardy-Weinberg equilibrium P-value >0.001) on 69 903 autosomal SNPs; (b) 12 290 SNPs obtained after pruning 54 404 SNPs for LD in each population using the parameter indep (50 5 0.5) in SNP and Variation Suite version 7 and (c) 4441 common SNPs for 50K and 80K platforms.…”

“…Analyses of population diversity and relationships based on ascertained SNP data produced incorrect results (Lachance and Tishkoff, 2013). LD-pruning (by removing closely associated SNPs) and analysis of haplotypes rather than individual SNPs could minimize ascertainment biases (Herráez et al, 2009). To determine the effects of ascertainment bias on indexes of population diversity and differentiation, we used different SNP data sets: pruned for LD (v. unpruned) and common to 50K and 80K platforms.…”

A Biologically Informed Method for Detecting Associations with Rare Variants

“…Using CEU/CHB/YRI populations as representative populations from the European, Asian, and African ancestral groups, the regions of natural selection associated with the gene list provided by Barreiro with overlap in one of two other publications are shown in Table 17 and Table 18 [84,95,96]. This table includes the number of loci in the bin, total binned variants from both populations, and the bin p-value.…”