皮肤色素沉着是人类中最突出和可变的表型之一。我们比较了来自人类色素沉着(HuPi)AmpliSeq™Custom面板的163个SNP和indel的等位基因,和生物地理祖先与上臂的定量皮肤色素沉着水平,下臂,和来自三个亚群的299名巴基斯坦人的前额:俾路支,普什图人,还有旁遮普.使用PrecisionID祖先小组估计每个个体的生物地理祖先。所有个体主要是中南亚和欧洲混合血统。然而,俾路支人也有撒哈拉以南非洲血统的平均比例约为10%,而旁遮普人和普什图人的比例<1%。普什图人之间的成对遗传距离,旁遮普人,和俾路支亚群基于祖先标记的差异有统计学意义。来自普什图人亚群体的个体的皮肤色素沉着在统计学上显著低于来自旁遮普人亚群体和俾路支人亚群体的个体(p<0.05)。欧洲和撒哈拉以南非洲血统的比例和五个SNP(rs1042602,rs10831496,rs1426654,rs16891982和rs12913832)与上臂的皮肤色素沉着有统计学意义。在多次测试校正后,巴基斯坦人群的下臂或前额(p<10-3)。基于这些SNP中的四个(rs1426654,rs1042602,rs16891982和rs12913832)的模型解释了上臂皮肤色素沉着的33%。四个SNP以及欧洲和撒哈拉以南非洲血统的比例解释了上臂皮肤色素沉着的37%。我们的结果表明,四个可能的致病SNP,rs1426654,rs1042602,rs16891982和rs12913832位于SLC24A5,TYR,分别为SLC45A2和HERC2,对混合的巴基斯坦亚群的肤色变化至关重要。
Skin pigmentation is one of the most prominent and variable phenotypes in humans. We compared the alleles of 163 SNPs and indels from the Human Pigmentation (HuPi) AmpliSeq™ Custom panel, and biogeographic ancestry with the quantitative skin pigmentation levels on the upper arm, lower arm, and forehead of 299 Pakistani individuals from three subpopulations: Baloch, Pashtun, and Punjabi. The biogeographic ancestry of each individual was estimated using the Precision ID Ancestry Panel. All individuals were mainly of mixed South-Central Asian and European ancestry. However, the Baloch individuals also had an average proportion of Sub-Saharan African ancestry of approximately 10%, whereas it was <1% in the Punjabi and Pashtun individuals. The pairwise genetic distances between the Pashtun, Punjabi, and Baloch subpopulations based on the ancestry markers were statistically significantly different. Individuals from the Pashtun subpopulation had statistically significantly lower skin pigmentation than individuals from the Punjabi and Baloch subpopulations (p < 0.05). The proportions of European and Sub-Saharan African ancestry and five SNPs (rs1042602, rs10831496, rs1426654, rs16891982, and rs12913832) were statistically significantly associated with skin pigmentation at either the upper arm, lower arm or forehead in the Pakistani population after correction for multiple testing (p < 10-3). A model based on four of these SNPs (rs1426654, rs1042602, rs16891982, and rs12913832) explained 33% of the upper arm skin pigmentation. The four SNPs and the proportions of European and Sub-Saharan African ancestry explained 37% of the upper arm skin pigmentation. Our results indicate that the four likely causative SNPs, rs1426654, rs1042602, rs16891982, and rs12913832 located in SLC24A5, TYR, SLC45A2, and HERC2, respectively, are essential for skin color variation in the admixed Pakistani subpopulations.