Unité de Génétique Forensique, Centre Universitaire Romand de Médecine Légale, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland.
Sci Rep. 2021 Nov 18;11(1):22530. doi: 10.1038/s41598-021-01940-w.
The OCA2-HERC2 locus is responsible for the greatest proportion of eye color variation in humans. Numerous studies extensively described both functional SNPs and associated patterns of variation over this region. The goal of our study is to examine how these haplotype structures and allelic associations vary when highly variable markers such as microsatellites are used. Eleven microsatellites spanning 357 Kb of OCA2-HERC2 genes are analyzed in 3029 individuals from worldwide populations. We found that several markers display large differences in allele frequency (10% to 35% difference) among Europeans, East Asians and Africans. In Europe, the alleles showing increased frequency can also discriminate individuals with (IrisPlex) predicted blue and brown eyes. Distinct haplotypes are identified around the variants C and T of the functional SNP rs12913832 (associated to blue eyes), with linkage disequilibrium r values significant up to 237 Kb. The haplotype carrying the allele rs12913832 C has high frequency (76%) in blue eye predicted individuals (30% in brown eye predicted individuals), while the haplotype associated to the allele rs12913832 T is restricted to brown eye predicted individuals. Finally, homozygosity values reach levels of 91% near rs12913832. Odds ratios show values of 4.2, 7.4 and 10.4 for four markers around rs12913832 and 7.1 for their core haplotype. Hence, this study provides an example on the informativeness of multiallelic markers that, despite their current limited potential contribution to forensic eye color prediction, supports the use of microsatellites for identifying causing variants showing similar genetic features and history.
OCA2-HERC2 基因座负责人类眼睛颜色变化的最大比例。许多研究广泛描述了该区域的功能 SNP 和相关变异模式。我们的研究目的是检查当使用高度可变的标记（如微卫星）时，这些单倍型结构和等位基因关联如何变化。在来自世界各地的 3029 个人中分析了跨越 OCA2-HERC2 基因 357 Kb 的 11 个微卫星。我们发现，几个标记在欧洲人、东亚人和非洲人之间的等位基因频率（10%至 35%的差异）存在较大差异。在欧洲，频率增加的等位基因也可以区分（IrisPlex）预测的蓝眼睛和棕色眼睛的个体。在功能 SNP rs12913832 的变异 C 和 T 周围确定了独特的单倍型（与蓝眼睛相关联），连锁不平衡 r 值高达 237 Kb。携带 rs12913832 C 等位基因的单倍型在预测为蓝眼睛的个体中具有高频率（76%在预测为棕色眼睛的个体中为 30%），而与 rs12913832 T 等位基因相关联的单倍型仅限于预测为棕色眼睛的个体。最后，rs12913832 附近的纯合度值达到 91%。围绕 rs12913832 的四个标记的比值比（OR）值分别为 4.2、7.4 和 10.4，其核心单倍型的 OR 值为 7.1。因此，这项研究提供了一个关于多等位基因标记信息性的例子，尽管它们目前对法医眼睛颜色预测的潜在贡献有限，但支持使用微卫星来识别具有类似遗传特征和历史的致病变异。
