Doctoral Dissertation Improvement: Genetics of Human Facial Variation

人类的面部特征显然受到强大的遗传控制。 同卵双胞胎的面部特征几乎无法区分，相关的个体表现出明显的家族相似性。患有特殊孟德尔病症的人具有一贯独特的面部特征。人类面部特征在世界各地也表现出广泛的正常变化。人类学家长期以来一直能够使用形态测量方法来量化这种变化，发现世界各地人群之间的许多相似之处和差异。虽然人们对不同人群的面部特征的形态学差异了解很多，但负责这些特征的潜在基因尚未确定。 大量的证据表明，一些等位基因对面部形态有很强的表型影响，但目前对这些基因的了解很少。本研究的目的是探讨混合个体的面部形态变异、遗传祖先和候选基因之间的关系。通过一个被称为混合作图的过程，有可能鉴定出在亲本群体之间差异的性状基因，这些性状对混合群体有贡献。 为了实现这一点，面部变异将使用几种形态测量方法从三维图像中量化，遗传变异将通过一组祖先信息标记来测量。 将从文献中确定候选基因的列表，并测试非中性进化的特征。 这些候选基因中的单核苷酸多态性将被测试对面部变异的影响，同时控制混合物导致的遗传分层。这些分析的结果将是识别的一些第一个基因参与面部形态的正常变化。 鉴于人类面部的进化和人类学意义，了解人类面部特征的正常变异是未来遗传学探索的重要方向。发现涉及面部变异的基因可以而且应该为我们对现代人类变异的理解提供新的见解，并为研究人类面部变异的进化提供了新的途径。

Human facial features are clearly under strong genetic control. Identical twins often have nearly indistinguishable facial features, and related individuals show notable familial resemblances. Persons affected with particular Mendelian conditions have consistently distinctive facial features. Human facial features also exhibit extensive normal variation throughout the world. Anthropologists have long been able to use morphometric measures to quantify this variation, finding many similarities within and differences among populations from around the world. While much is known about morphological variation in facial features among populations, the underlying genes that are responsible for these traits have yet to be identified. Abundant evidence suggests that some alleles have strong phenotypic effects on facial morphology, but very little is currently known about these genes. The aim of this project is to investigate the relationships among morphological variation of the face, genetic ancestry and candidate genes in a sample of admixed individuals. Through a process known as admixture mapping, it is possible to identify genes for traits which vary between the parental populations that contributed to the admixed population. To accomplish this, facial variation will be quantified from three-dimensional images using several morphometric methods and genetic variation will be measured via a panel of ancestry-informative markers. A list of candidate genes will be identified from the literature and tested for signatures of non-neutral evolution. Single-nucleotide polymorphisms in these candidate genes will be tested for effects on facial variation while controlling for genetic stratification resulting from admixture. The results of these analyses will be the identification of some of the first genes involved in normal variation in facial morphology. Given the evolutionary and anthropological significance of the human face, understanding normal variation in human facial features is an important direction for future genetic exploration. Finding genes involved in facial variation can and should provide new insights into our understanding of modern human variation and presents a new avenue for investigating the evolution of human facial variation.