Identifying the genetic architecture of pigmentary traits in populations of diverse ancestry

识别不同血统人群色素特征的遗传结构

• 批准号: RGPIN-2016-06353
• 负责人: Parra, Esteban
• 金额: $ 3.93万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=690452
• 关键词: Identifying; genetic; architecture; pigmentary; traits

The remarkable variation in skin, hair and iris pigmentation observed in human populations is due to differences in the amount, type and distribution of melanin, which is synthesized by specialized cells known as melanocytes. The detailed picture of the genes involved in these traits remains far from complete. In particular, very few studies have focused on the genetics of pigmentation in non-European populations, in spite of the fact that quantitative studies of skin, hair and iris color in these populations show that there is substantial diversity in these traits. ******In this project, I propose to identify genetic markers responsible for normal variation in skin, hair and iris colour, as well as iris structure, in a large sample of individuals of diverse ancestry (3,000 individuals of East Asian, European and South Asian ancestry, 1,000 per group). Detailed quantitative measures of skin and hair pigmentation (using reflectance spectroscopy), and iris colour and structure (using high-resolution photography), will be obtained for each individual, and a microarray will be used to characterize more than 1.7 million genetic markers throughout the genome. This will make it possible to evaluate the association of the genetic markers with pigmentary traits and iris structure. ******Pigmentation is a particularly fascinating phenotype to study in human populations, because in many respects it is an atypical trait. Numerous genetic studies have indicated that the average proportion of genetic variation due to differences between major continental groups is just 10-15% of the total genetic variation. In contrast, pigmentary traits show large differences between continental populations. The reasons for this discrepancy can be traced back primarily to the strong influence of natural selection, which has shaped the distribution of pigmentation according to a clear latitudinal gradient. The proposed systematic study of pigmentary phenotypes in populations of diverse ancestry is important from evolutionary, genetic, and anthropological points of view; it will clarify the connection between the molecular variation and the phenotypic diversity observed in our species, while providing insights on how diverse factors (particularly natural selection) have shaped the evolution of pigmentation and pigmentation genes. The research is also relevant from a biomedical perspective, given that many variants associated with common pigmentation variation are also associated with skin cancer risk. Finally, this project will explore the genetic architecture of iris structure (e.g., contraction furrows, Fuchs' crypts, nevi, and Wolfflin nodules). These traits show substantial variation in human populations, but very few studies have been devoted to the identification of the genetic factors underlying this variation.

在人群中观察到的皮肤、头发和虹膜色素沉着的显着变化是由于黑色素的数量、类型和分布的差异造成的，黑色素是由称为黑素细胞的特殊细胞合成的。与这些性状相关的基因的详细情况还远未完成。特别是，很少有研究关注非欧洲人群的色素沉着遗传学，尽管对这些人群的皮肤、头发和虹膜颜色的定量研究表明这些特征存在很大的多样性。 ******在这个项目中，我建议在不同血统的个体大样本（3,000 名东亚、欧洲和南亚血统个体，每组 1,000 名）中确定导致皮肤、头发和虹膜颜色以及虹膜结构正常变化的遗传标记。将为每个人获得皮肤和头发色素沉着（使用反射光谱）以及虹膜颜色和结构（使用高分辨率摄影）的详细定量测量，并将使用微阵列来表征整个基因组中超过 170 万个遗传标记。这将使评估遗传标记与色素特征和虹膜结构的关联成为可能。 ******色素沉着是在人群中研究的一个特别令人着迷的表型，因为在许多方面它是一种非典型特征。大量的遗传学研究表明，由于主要大陆群体之间的差异而导致的遗传变异的平均比例仅占总遗传变异的10-15%。相比之下，大陆种群之间的色素特征显示出巨大差异。造成这种差异的原因主要可以追溯到自然选择的强烈影响，它根据明显的纬度梯度塑造了色素沉着的分布。从进化、遗传和人类学的角度来看，对不同血统人群色素表型的系统研究很重要。它将阐明我们物种中观察到的分子变异和表型多样性之间的联系，同时提供有关不同因素（特别是自然选择）如何影响色素沉着和色素沉着基因进化的见解。从生物医学的角度来看，这项研究也具有相关性，因为许多与常见色素沉着变异相关的变异也与皮肤癌风险相关。最后，该项目将探索虹膜结构的遗传结构（例如收缩沟、福克斯隐窝、痣和沃尔夫林结节）。这些特征在人群中表现出巨大的差异，但很少有研究致力于识别这种差异背后的遗传因素。