Discovery of ethnicity-specific SNPs
We identified ethnicity-specific SNPs by eliminating common SNPs from HapMap samples and mapped the SNP positions to the UCSC RefGene lists. 22, 25, three 332 genes were identified in the CEU, in the JPT individuals, and in the YRI individuals, respectively (Fig. 1). Comparison of the three sets showed that YRI individuals had a biased order of SNP-based genes. This result was a consensus among previous evolutionary findings. CEU and JPT belong to the same cluster, together with Amerindians and Australopapuan, while YRI belongs to a separate cluster showing the first split between Africans and non-Africans [16, 17]. African populations subdivided from other sub-Saharan African populations, and a small subset of this population migrated out of Africa in the past 100,000 years. African and non-African populations divided in the past 40,000 years. Phylogenetic analysis of Y chromosomal haplotypes, mtDNA, and autosomes are indicative of the longest history of population subdivision in Africa. Africans are the most ancestral population in human and have fewer sites in linkage disequilibrium, compared with non-African populations [18].
To explore the meaningful biological information of structural variations, we performed GSEA for the SNP-based genes using GO categories (BP, CC, and MF) in the DAVID tool. The significantly categorized functions (p < 0.01) of SNP-based genes for YRI are shown as pie charts in Fig. 2, but none was significantly enriched for CEU and JPT. Six groups of BP and four groups of MF had significant enrichment score ranges of 1.67-4.85 and 7.16E-04-0.002, respectively. The top pie chart in BP presents G-protein-coupled receptor protein signaling pathway, including chemotaxis, and defense response to bacterium (Fig. 2A). In the enriched region, 8% of BP was chemotaxis (GO: 0006935) with an enrichment score of 3.88. Chemotaxis contributes to enhancement of disease aggressiveness in African-Americans [19]. The MFs that were significantly enriched were G-protein-coupled receptor activity and binding, olfactory receptor activity, and transmembrane receptor activity (Fig. 2B). Enriched functions in cellular components were keratin filament (GO:0045095) with an enrichment score of 5.86, which contained the KRTAP gene family (KRTAP12-3, KRTAP4-11, KRT14, KRTAP4-4, KRTAP9-8, KRTAP10-7, KRTAP10-8). KRTAP genes are up-regulated in white hair than in black hair by a microarray analysis. Immunoreactivity for KRTP genes in white hair follicles was increased compared with black hair. Therefore Choi et al. [20] suggested that greying hair, a sign of aging, is associated with hair growth rate.