3D Analysis of Normal Facial Variation: Data Repository and Genetics (Research)

描述（由申请人提供）：尽管有充分的证据表明面部外观和结构是高度可遗传的，但关于特定基因的变异如何与我们物种中明显的面部形态多样性相关的信息缺乏。随着经济实惠的非侵入性3D表面成像技术的出现，现在可以捕获大量个体面部的详细定量信息。通过将最先进的3D成像技术与高通量基因分型技术的进步相结合，存在一个无与伦比的机会来绘制正常面部变异的遗传决定因素。提高对基因型和面部表型之间关系的理解可能有助于阐明影响常见颅面异常，特别是口面裂的因素，这是人类最普遍的出生缺陷之一。该建议有两个主要目标：(1)构建一个非本地的3D面部和遗传数据存储库；(2)利用该数据存储库识别影响正常面部中部变异的基因。第一个目标将侧重于数据生成和资源开发，并将涉及从一般人群中收集3500名健康高加索人（5-40岁）的3D面部表面图像和DNA样本。将从3D图像中提取定量面部测量数据，并对所有DNA样本进行全基因组SNP标记的基因分型。与FaceBase hub一起工作，我们的目的是创建一个可扩展的。可供外部调查人员使用的交互式和可挖掘的数据资源，包括面部测量，3D图像和基因型。最终，希望这样一个数据库能够促进新的研究活动。为了说明这一潜力，本提案的第二个目标将集中在识别与面中形态变异相关的snp，包括与口面部裂易感性相关的面部特征。面部中形态的显著测量将从3D面部表面图像中得到，然后将采用全基因组关联方法来识别影响感兴趣的面部特征定量变化的多态性。

DESCRIPTION (provided by applicant): Although ample evidence exists that facial appearance and structure are highly heritable, there is a dearth of information regarding how variation in specific genes relates to the diversity of facial forms evident in our species. With the advent of affordable, non-invasive 3D surface imaging technology, it is now possible to capture detailed quantitative information about the face in a large number of individuals. By coupling state- of-the-art 3D imaging with advances in high-throughput genotyping, an unparalleled opportunity exists to map the genetic determinants of normal facial variation. An improved understanding of the relationship between genotype and facial phenotype may help illuminate the factors influencing liability to common craniofacial anomalies, particularly orofacial clefts, which are among the most prevalent birth defects in humans. This proposal has two major goals: (1) to construct a nonnative repository of 3D facial and genetic data and (2) to utilize this data repository to identify genes that influence normal midfacial variation. The first goal will focus on data generation and resource development and will involve the collection of 3D facial surface images and DNA samples on 3500 healthy Caucasian individuals (age 5-40) drawn from the general population. Quantitative facial measures will be extracted from the 3D images and all DNA samples will be genotyped for genome-wide SNP markers. Working in conjunction with the FaceBase hub, our intent is to create a scalable. Interactive and minable data resource available to outside investigators, which will contain facial measures, 3D images and genotypes. Ultimately, it is hoped that such a database w\\ facilitate novel research initiatives. To illustrate this potential, the second goal of this proposal will focus on identifying SNPs associated with variation in midfacial morphology, including those facial features relevant to orofacial cleft predisposition. Salient measures of midfacial morphology will be derived from 3D facial surface images, and a genome-wide association approach will then be employed to identify polymorphisms that influence quantitative variation in the facial features of interest. PUBLIC HEALTH RELEVANCE: Our proposal to establish a 3D facial and genetic marker database will benefit both the research and clinical community, by providing a resource to both test new hypotheses related to normal and abnormal craniofacial development and serve as a repository for normative control data. Furthermore, this project has the potential to identity genetic risk factors important for orofacial clefting.