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

这项研究旨在确定导致美洲原住民在向新大陆扩张后皮肤色素沉着变黑的基因。随着人口从北纬地区迁移到南纬地区，深色皮肤更能抵御紫外线辐射的伤害。对这些基因的研究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和美洲土著混合血统的个体中进行，这些地方的紫外线辐射水平很高。研究了82个与皮肤色素沉着变异相关的基因，以寻找自然选择的证据。在表现出最强选择证据的12个基因中，48个单核苷酸多态性（SNPs）代表了选择提名候选基因的总体变异，将在混合祖先个体中进行基因分型。这些单核苷酸多态性显示亲代人群之间存在显著的等位基因频率差异，因此负责皮肤色素变化的基因可以通过在肤色较深的个体中过量的美洲原住民等位基因来识别。这种混合连锁分析对于研究皮肤色素沉着等性状尤其有效，因为这种方法比标准关联研究需要更少的总标记。这项研究具有重要的智力价值，因为皮肤色素沉着是印第安人在分散到新大陆时遇到的波动环境中复杂特征进化的理想模型。然而，以前的研究人员在很大程度上忽略了这些人群。对皮肤色素沉着进化的进一步了解也有更广泛的影响，包括理解导致皮肤颜色持续变化的选择压力，这种变化经常被错误地认为是一种“种族”特征。此外，法医研究人员对从未知DNA样本中预测肤色的能力很感兴趣。最后，这笔赠款将用于培训一名女研究生，这是该领域代表性不足的群体。

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.