Investigating the genetic basis of human skeletal facial morphology

研究人类骨骼面部形态的遗传基础

• 批准号: 10438980
• 负责人: Susan Walsh
• 金额: $ 46.83万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10438980
• 关键词: 3-Dimensional; Back; Bone Tissue; Bone structure; Classification; Cleft Lip; Collection; Complement; Computer Analysis; Data; Development; Developmental Biology; Diagnostic; Disease; Encapsulated; Ensure; Equipment; Etiology; Euclidean Space; Face; Forensic Medicine; Future; Gene Expression; Genes; Genetic; Genome; Genotype; Glean; Goals; Human; Image; Imagery; Individual; Institutional Review Boards; Instruction; Knowledge; Lead; Link; Maps; Masks; Massive Parallel Sequencing; Measures; Medical Genetics; Methodology; Methods; Morphology; Normal Range; Operative Surgical Procedures; Other Genetics; Phenotype; Play; Procedures; Publications; Publishing; Reconstructive Surgical Procedures; Regulator Genes; Reporting; Research; Scanning; Shapes; Signal Transduction; Skeletal bone; Skin; Standardization; Stereophotogrammetries; Structure; Surface; Testing; Therapeutic Intervention; Thick; Time; Tissues; Variant; Visual; Work; assay development; base; bone; cohort; cone-beam computed tomography; craniofacial; craniofacial bone; design; experience; face bone structure; gene discovery; genetic analysis; genetic association; genetic variant; genome wide association study; human subject; improved; innovation; insight; interest; malformation; personalized therapeutic; sex; skeletal; soft tissue; success; three dimensional structure

PROJECT SUMMARY/ABSTRACT The human face consists of unique structures that form our identity. We have strong evidence that human craniofacial variation has a high genetic component, influenced by ancestry and sex. The effort to improve our understanding of ‘normal-range’ facial variation has been of great interest in the last decade as it has particular implications for understanding the etiology of malformations in the face related to disease. Recently, an advancement in phenotyping towards the use of quasi-landmarks applied to 3D facial scans has enriched our knowledge with new genetic links tied to the human face. However, these and other genetic signals may potentially be clouded by not knowing facial skeletal information underneath the skin. A complete examination of human facial structure would be to inspect both the outer soft tissue structure and the inner hard tissue bone concurrently, including the depth of tissue in their connection. From our ever-expanding list of craniofacial candidate variants/genes, it is more important than ever to accurately classify their specific contribution to the face’s development through accurate landmark placement, and correction of competing structures within the facial construct. By doing this, we effectively provide a more precise classification of the facial link, whether it is directed towards tissue or bone variation. This more explicit definition will allow a more efficient examination of how these variants work in tandem for downstream gene expression and functional analyses work. This insight would also pave the way for more accurate personalized therapeutic interventions for craniofacial treatment and surgery, not to mention a more complete face visual for diagnostics. The current proposal has two aims designed to significantly advance our current understanding of normal-range human craniofacial variation: (1) We will enhance current mesh landmarking procedures by building a dense (thousands) map of vertices across the human skeletal bone, effectively generating a craniofacial skeletal mask using quasi-landmarks, which has not yet been made available in the field. This template will allow efficient normalized landmarking of craniofacial bone using MeshMonk registration; (2) Utilizing a new collection of Cone Beam Computed Tomography facial scans (n=750), allows us to connect both soft tissue with hard tissue landmarks ensuring one is a covariate against the other facial structure being examined and perform association testing with a list of over 350 facial candidate variants/genes. This more precise method of phenotype:genotype association has not yet been characterized in such a manner, correcting bone from soft tissue and vice versa. For the first time, we shall also generate Facial Soft Tissue Thickness (FSTT) at quasi-landmarks by utilizing the information gleaned from these two structural entities and their connection in space. This project aims to confirm, with genetic association, a more complete methodology for concurrent facial landmarking of all structures in the human face, both externally and internally, and complement with visuals that explain the additive genetic effects of some of the currently most interesting variants/genes discovered for human facial variation.

项目摘要/摘要 人脸由形成我们身份的独特结构组成。我们有强有力的证据表明人类 颅面变异具有很高的遗传成分，受祖先和性别影响。改善我们的努力 在过去的十年中，对“正常范围”面部变化的理解引起了人们的极大兴趣 了解与疾病有关的畸形的病因的含义。最近， 在3D面部扫描中使用的准地标的表型的进步已经丰富了我们 与人脸相关的新遗传联系的知识。但是，这些和其他遗传信号可能 不知道皮肤下面的面部骨骼信息可能会蒙上阴影。完整的检查 人的面部结构是检查外部软组织结构和内部硬组织骨 同时，包括组织深度。从我们不断扩大的颅面清单中 候选变体/基因，准确地对其针对其特定贡献进行分类比以往任何时候都重要 通过准确的地标放置以及对竞争结构的纠正，面对面的发展 面部结构。通过这样做，我们有效地提供了面部链接的更精确的分类，无论是 针对组织或骨骼变异。这个更明确的定义将允许对 这些变体如何在串联中起作用，以使下游基因表达和功能分析起作用。这个见解 还将为更准确的个性化治疗干预措施铺平道路，以进行颅面治疗和 手术，更不用说诊断更完整的视觉效果。当前的提案有两个目标 为了显着提高我们目前对正常范围人类颅面变异的理解：（1）我们将 通过在整个上建立密集的（数千）顶点图来增强目前的网格地标性程序 人体骨骼骨，有效地使用准地标生成颅面骨骼面膜 在现场可用。该模板将允许有效的颅面标准化地标 使用Meshmonk注册的骨头； （2）利用新的锥束计算机断层扫描面部护理 扫描（n = 750），使我们能够将两个软组织与硬组织地标连接起来，以确保一个是协变量的 反对检查的其他面部结构，并与350多个面部的列表进行关联测试 候选变体/基因。这种更精确的表型方法：基因型关联尚未 以这种方式进行特征，从软组织中校正骨头，反之亦然。我们也是第一次 通过使用从这些信息中收集的信息，在准地标生成面部软组织厚度（FSTT） 两个结构实体及其在太空中的联系。该项目旨在与遗传关联确认 更完整的方法，用于同时在人脸上所有结构的面部地标，两者在外部 内部，并配有视觉效果，这些视觉效果可以解释某些当前的添加性遗传效应 最有趣的变体/基因是针对人面部变异的。