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

描述(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状多样性相关的信息很少。随着负担得起的非侵入性3D表面成像技术的出现，现在可以捕获大量个体关于面部的详细定量信息。通过将最先进的3D成像与高通量基因分型的进步相结合，存在着绘制正常面部变异的遗传决定因素的无与伦比的机会。更好地理解基因和面部表型之间的关系可能有助于阐明影响常见头面部畸形易感性的因素，特别是口面部裂，这是人类最常见的出生缺陷之一。这项建议有两个主要目标：(1)构建一个3D面部和基因数据的非本地存储库；(2)利用这个数据存储库来识别影响正常面中部变异的基因。第一个目标将侧重于数据生成和资源开发，并将涉及从普通人群中抽取3500名健康的高加索人(5-40岁)的3D面部表面图像和DNA样本的收集。将从3D图像中提取定量的面部测量数据，并将对所有DNA样本进行全基因组SNP标记的基因分型。与FaceBase中心合作，我们的目标是创建一个可伸缩的。外部调查人员可使用的交互式和可挖掘的数据资源，其中将包含面部测量、3D图像和基因类型。最终，人们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，这项建议的第二个目标将集中在识别与面中部形态变异相关的SNPs，包括那些与口裂易感性相关的面部特征。面部中部形态的显著测量将从3D面部表面图像中获得，然后将使用全基因组关联方法来识别影响感兴趣面部特征的数量变异的多态。 公共卫生相关性：我们建立3D面部和遗传标记数据库的建议将使研究和临床社区受益，因为它提供了一种资源，既可以测试与正常和异常颅面发育相关的新假说，也可以作为标准对照数据的储存库。此外，该项目有可能确定对口裂重要的遗传风险因素。

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.