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

博士论文改进：涉及美洲原住民色素沉着的基因的鉴定和研究。

• 批准号: 0925976
• 负责人: Mark Shriver
• 金额: $ 0.93万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2010-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0925976&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Improvement; Identification; Investigation

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.

这项研究旨在鉴定出在扩展到新世界后，使土著美国人的皮肤色素沉着变暗的基因。 随着种群从北部迁移到南部的纬度，较深的皮肤更适应性，因为可以防止损害超紫外线辐射。 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和土著祖先的个体中进行，其中超紫外线在高水平。 研究了与皮肤色素沉着变化相关的82个基因，以证明自然选择的证据。 在表现出选择最有力证据的12个基因中，代表选择指定候选基因的总体变异的48个单核苷酸多态性（SNP）将在混合血统个体中进行基因分型。 这些SNP在父母种群之间显示出很大的等位基因频率差异，因此可以通过该基因在皮肤较深的个体中的该基因中过多的美国本地等位基因来鉴定出负责皮肤色素沉着变化的基因。 这种混合链接分析对于研究皮肤色素沉着等性状特别有力，在父母种群之间有很大的不同，因为该方法比标准关联研究所需的总标记少。这项研究具有很大的智力优点，因为皮肤色素沉着是在散布到新世界的土著美国人遇到的波动环境中复杂性状发展的理想模型。 但是，以前的研究人员在很大程度上忽略了这些人群。 对皮肤色素沉着的演变的越来越多的理解也具有更广泛的影响，包括了解导致连续肤色变化的选择性压力，这通常被错误地认为是“种族”特征。 此外，法医研究人员对从未知DNA样品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性研究生，这是该领域的一个代表性不足的小组。