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.

这项研究旨在确定基因导致皮肤色素沉着变暗的土著美国人后，扩展到新的世界。 随着人口从北方迁移到南半球，深色皮肤更能适应紫外线辐射的伤害。 对这些基因的研究将在来自紫外线辐射水平高的新墨西哥州、科罗拉多、墨西哥和哥伦比亚的欧洲人和美洲土著血统的混合个体中进行。 研究人员调查了82个与皮肤色素变化相关的基因，以寻找自然选择的证据。 在显示出最强选择证据的12个基因中，将在混合血统的个体中对代表选择提名的候选基因中的总体变异的48个单核苷酸多态性（SNP）进行基因分型。 这些SNPs在亲本群体之间显示出相当大的等位基因频率差异，因此可以通过在具有较深皮肤的个体中该基因处过量的美洲原住民等位基因来鉴定负责皮肤色素沉着变化的基因。 这种混合物的连锁分析是特别强大的研究性状，如皮肤色素，父母之间的人口差异很大，因为这种方法需要更少的总标记比标准的关联研究。这项研究有很大的学术价值，因为皮肤色素沉着是一个理想的模型，复杂的性状在波动的环境中遇到的土著美国人分散到新的世界。 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更多了解也具有更广泛的影响，包括理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。