The Genetics of Normal Variation in Human Pigmentation

描述（由申请人提供）：本研究的目的是确定导致人眼、头发和皮肤颜色正常变异的基因和多态性。我们对人类色素沉着基因的了解大多来自于对导致眼皮肤白化病（OCA）的基因突变的研究。与OCA相关的许多基因多态性可能以微妙或定量的方式影响基因功能，并有望对色素表型产生类似的影响。一般的方法是基于从亚利桑那大学和斯坦福大学收集的1000个DMA样本进行大规模的关联研究。所有样品将对3个候选基因的snp进行基因分型。该提议的一个潜在假设是，TYR、TYRP1和/或ASIP基因表达的遗传变异有助于正常表型变异。将进行一项关联研究，以将人类色素沉着基因调控区域多态性位点的变异与表型变异联系起来。这项工作将为人类多样性的遗传因素提供更深入的认识，并为研究多基因与环境因素相互作用导致的人类疾病提供模型。

DESCRIPTION (provided by applicant): The goal of this study is to identify the genes and polymorphisms that contribute to normal variation in human eye, hair, and skin color. Much of our understanding of human pigmentation genes come from studies of mutations in genes resulting in oculocutaneous albinism (OCA). Many polymorphisms in genes associated with OCA are likely to affect gene function in a subtle or quantitative way, and are expected to have similar effects on pigmentary phenotypes. The general approach will be to carry out a large-scale association study based on 1000 DMA samples collected from subjects at the University of Arizona and Stanford University. All samples will be genotyped for SNPs at 3 candidate genes. An underlying hypothesis of this proposal is that genetic variation in the expression of the TYR, TYRP1, and/or ASIP genes contributes to normal phenotypic variation. An association study will be performed to correlate the variation in polymorphic sites of regulatory regions of human pigmentation genes with phenotypic variation. This work will provide a deeper understanding of the genetic factors that contribute to human diversity and a model for studying human diseases caused by interaction between multiple genes and environmental factors.