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 人脸由独特的结构组成，这些结构形成了我们的身份。我们有强有力的证据证明人类 颅面变异有很高的遗传成分，受祖先和性别的影响。努力改善我们的 在过去的十年里，对正常范围面部变异的理解一直是人们非常感兴趣的，因为它具有特殊的 对理解与疾病相关的面部畸形的病因学的启示。最近，一位 在应用于3D面部扫描的准地标的表型鉴定方面的进展丰富了我们的 具有与人脸相关的新基因联系的知识。然而，这些和其他遗传信号可能 可能会因为不知道皮肤下的面部骨骼信息而蒙上阴影。一次全面的检查 对人类面部结构的检查将同时检查外部软组织结构和内部硬组织骨 同时，包括它们连接的组织的深度。从我们不断扩大的颅面名单中 候选变异体/基因，比以往任何时候都更重要的是准确地分类它们对 通过准确的地标放置和纠正内部竞争结构来实现Face的发展 面部构造。通过这样做，我们有效地提供了面部联系的更准确的分类，无论是 指向组织或骨骼的变异。这一更明确的定义将允许更有效地检查 这些变异如何协同作用于下游基因表达和功能分析。这种洞察力 也将为更准确的个性化治疗干预头面部治疗铺平道路 手术，更不用说用于诊断的更完整的面部视觉。目前的提案设计了两个目标 为了显著提高我们目前对正常范围的人类颅面变异的理解：(1)我们将 通过构建密集(数千)的顶点地图来增强当前的网格地标程序 人类骨骼，使用准地标有效地生成了头面部骨骼面具，这还没有 但仍可在现场使用。此模板将允许对颅面部进行有效的归一化标记 使用MeshMonk配准的骨骼；(2)使用新的锥束计算机断层扫描面部集合 扫描(n=750)，使我们能够将软组织和硬组织标志物连接起来，确保其中一个是协变量 对照正在检查的其他面部结构，并执行与超过350个面部的列表的关联测试 候选变异/基因。这种更精确的表型方法：基因型关联尚未被 以这种方式为特征的，从软组织矫正骨骼，反之亦然。第一次，我们还将 利用从这些信息收集的信息，在准地标处生成面部软组织厚度(FSTT 两个结构实体及其在空间上的联系。该项目旨在通过基因关联来确认一种 更完整的方法，用于同时对人脸中的所有结构进行面部标记，包括外部 在内部，并与解释当前某些基因的相加遗传效应的视觉效果相补充 人类面部变异发现的最有趣的变异/基因。