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.

项目概要/摘要 人脸由构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，受血统和性别的影响。努力改善我们的 在过去的十年中，对“正常范围”面部变化的理解引起了人们极大的兴趣，因为它具有特殊的意义 对于了解与疾病相关的面部畸形的病因学具有重要意义。最近，一个 表型分析在使用准地标应用于 3D 面部扫描方面取得的进展丰富了我们的研究 与人脸相关的新遗传联系的知识。然而，这些和其他遗传信号可能 由于不了解皮肤下的面部骨骼信息，可能会变得模糊。完整的检查 人体面部结构的检测是同时检查外部软组织结构和内部硬组织骨骼 同时，包括它们连接的组织深度。从我们不断扩大的颅面列表中 候选变异/基因，准确分类它们对基因的具体贡献比以往任何时候都更加重要 通过准确的地标放置和校正内部竞争结构来实现面部的发展 面部构造。通过这样做，我们有效地提供了更精确的面部链接分类，无论是 针对组织或骨骼变化。这个更明确的定义将允许更有效地检查 这些变体如何协同工作以进行下游基因表达和功能分析。这种洞察力 也将为更准确的颅面治疗个性化治疗干预铺平道路 手术，更不用说用于诊断的更完整的面部视觉。当前的提案有两个目的 显着推进我们目前对正常范围的人类颅面变异的理解：（1）我们将 通过构建跨越整个网格的密集（数千个）顶点图来增强当前的网格地标程序 人类骨骼，利用准地标有效地生成颅面骨骼掩模，这在目前还没有 尚未在现场提供。该模板将允许颅面的有效标准化标志 使用MeshMonk注册骨骼； (2) 利用新的锥形束计算机断层扫描面部 scans (n=750), allows us to connect both soft tissue with hard tissue landmarks ensuring one is a covariate 与正在检查的其他面部结构进行对比，并对超过 350 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：基因型关联方法尚未被采用 以这种方式表征，从软组织中矫正骨骼，反之亦然。我们还将首次 利用从这些准地标收集的信息生成面部软组织厚度 (FSTT) 两个结构实体及其在空间中的连接。该项目旨在通过遗传关联来确认 更完整的方法，用于同时对人脸所有结构（包括外部结构）进行面部标记 和内部，并补充视觉效果，解释当前一些基因的附加遗传效应 人类面部变异中发现的最有趣的变异/基因。