Doctoral Dissertation Improvement: Identification and Investigation of Genes Involved in Indigenous American Pigmentation.

这项研究试图确定导致美洲原住民在扩张到新大陆后皮肤色素沉着变黑的基因。随着人口从北纬迁徙到南纬，较黑的皮肤更适合保护自己免受紫外线辐射的伤害。对这些基因的搜索将在来自新墨西哥州、科罗拉多州、墨西哥和哥伦比亚的欧洲人和土著美国人混合血统的个人身上进行，这些地方的紫外线辐射水平很高。对82个与皮肤色素沉着变化相关的基因进行了研究，以寻找自然选择的证据。在12个表现出最强选择证据的基因中，代表被选候选基因总体变异的48个单核苷酸多态(SNPs)将在混合血统的个体中进行基因分型。这些SNP在亲代群体之间显示出显著的等位基因频率差异，因此可以通过深色皮肤个体中该基因上过多的美洲原住民等位基因来识别导致皮肤色素沉着变化的基因。这种混合连锁分析对于研究皮肤色素沉着等性状特别有效，因为这种方法需要的总标记比标准的关联研究少，这些性状在亲本群体之间存在很大差异。这项研究有很大的智力价值，因为皮肤色素沉着是在美洲土著人散居到新大陆所遇到的波动环境中复杂特征进化的理想模式。然而，之前的研究人员在很大程度上忽略了这些群体。加深对皮肤色素沉着进化的了解也有更广泛的影响，包括理解导致持续肤色变化的选择性压力，这经常被错误地认为是一种“种族”特征。此外，法医研究人员还对从未知DNA样本中预测肤色的能力感兴趣。最后，这笔赠款将有助于培训一名女研究生，这是这一领域中代表性不足的群体。

This study seeks to identify genes causing darkening of skin pigmentation in Indigenous Americans following expansion into the New World. As populations migrated from northern into southern latitudes, darker skin was more adaptive as protection against damage from ultra-violet radiation. The search for these genes will be conducted in individuals of admixed European and Indigenous American ancestry from New Mexico, Colorado, Mexico and Colombia where ultra-violet radiation is at high levels. 82 genes associated with variation in skin pigmentation were investigated for evidence of natural selection. In the 12 genes showing the strongest evidence of selection, 48 single nucleotide polymorphisms (SNPs) representing the overall variation in the selection nominated candidate genes will be genotyped in individuals of admixed ancestry. These SNPs show substantial allele frequency differences between the parental populations so the genes responsible for variation in skin pigmentation can be identified by an excess of Indigenous American alleles at that gene in individuals with darker skin. This admixture linkage analysis is especially powerful for studying traits like skin pigmentation which vary substantially between the parental populations because this methodology requires fewer total markers than a standard association study. There is substantial intellectual merit in this study because skin pigmentation is an ideal model for the evolution of complex traits in the fluctuating environments encountered by Indigenous Americans dispersing into the New World. However, previous researchers have largely ignored these populations. An increased understanding of the evolution of skin pigmentation also has broader impacts including understanding the selective pressures causing continuous skin color variation which is often mistakenly thought of as a 'racial' trait. Additionally, forensic researchers are interested in the ability to predict skin color from an unknown DNA sample. Finally, this grant will contribute to the training of a female graduate student, an under-represented group in this field.