Doctoral Dissertation Improvement: Genetics of Human Facial Variation

人类的面部特征显然受到强烈的基因控制。同卵双胞胎的面部特征几乎无法区分，而相关个体则表现出显著的家族相似性。患有特定孟德尔病症的人具有一贯独特的面部特征。人类的面部特征在世界各地也表现出广泛的正常变化。长期以来，人类学家一直能够使用形态计量学方法来量化这种差异，发现世界各地人群之间存在许多相似之处和差异。虽然人们对人群中面部特征的形态变化了解甚多，但导致这些特征的潜在基因尚未被确定。大量证据表明，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甚少。本研究的目的是研究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。通过一种称为混合作图的方法，可以鉴定出构成混合群体的亲本群体之间不同性状的基因。为了实现这一目标，面部变异将使用几种形态计量学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。候选基因列表将从文献中确定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，同时控制由混合引起的遗传分层。这些分析的结果将是识别一些涉及面部形态正常变异的第一批基因。鉴于人脸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基因探索的重要方向。发现与面部变异有关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.