Genetic Architecture of the Human Dentognathic Complex

人类牙颌复合体的遗传结构

• 批准号: 8055495
• 负责人: Richard J Sherwood
• 金额: $ 70.44万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-18 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8055495
• 关键词: Address; Adult; Affect; Architecture; Biological; Cleft Palate; Complex; Computer software; Congenital Abnormality; Crowding; Data; Data Set; Deformity; Dental; Dental Care; Dental arch structure; Dental caries; Dentition; Development; Diet; Disease; Dysmorphology; Environment; Environmental Risk Factor; Epidemiology; Esthetics; Etiology; Foundations; Future; Genes; Genetic; Genetic Markers; Genetic Variation; Goals; Growth; Health; Helminths; Heritability; Human; Individual; Infection; Inherited; Investigation; Jaw; Knowledge; Length; Malocclusion; Mandible; Maxilla; Measurement; Measures; Mediating; Methods; Metric; Minor; Modeling; Morphology; Mutation; National Institute of Dental and Craniofacial Research; Nature; Nepal; Outcome; Palate; Participant; Phenotype; Population; Public Health; Quantitative Genetics; Quantitative Trait Loci; Recording of previous events; Research; Resources; Rest; Risk; Rodent Model; Rotation; Series; Shapes; Solid; Strategic Planning; Techniques; Tissue Engineering; Tooth structure; United States National Institutes of Health; Variant; Width; Work; base; cranium; dental casting; design; gene discovery; gene environment interaction; gene interaction; gene therapy; genetic analysis; genetic linkage analysis; genetic pedigree; impression; member; orofacial; programs; repaired; sex; trait

DESCRIPTION (provided by applicant): The ultimate objective of the proposed study is to discover genes influencing variation in human dentognathic morphology. This will be accomplished through a series of analyses aimed at elucidating fundamental aspects of the genetic architecture of the human dentognathic complex. Significant health problems related to the dentition and jaws (the dentognathic complex) range from aesthetic issues due to malocclusion, to increase risk of caries, impaction, and infection due to dental crowding, to significant congenital deformities (e.g., orofacial clefting). The etiology of dentognathic disorders is complex. Both hereditary and environmental factors have been identified as factors influencing the variation of these traits. The proposed study is designed to examine normal variation in, and the relationships between, dentognathic traits in a population where environmental factors (diet, dental care) are relatively homogeneous. We contend that an understanding of the influences genetic and environmental factors have on the dentognathic complex must rest on a solid foundation of detailed knowledge of the genetic components underlying the development of normal variation. Understanding the nature of genetic influences on the regions of the cranium is of critical importance to a wide variety of clinicians. As it becomes increasingly possible to incorporate gene therapy and tissue engineering when approaching repair of orofacial dysmorphology, studies elucidating the genetic underpinnings of continuous phenotypes typifying normal morphological variation are of critical importance. Examination of genetic contributions to normal variation in the dentognathic complex will be addressed in two specific aims: 1) Characterize variation in biomedically-relevant phenotypes describing dental and dental arcade morphology and explore fundamental aspects of the genetic architecture of dentognathic morphology. 2) Identify chromosomal regions (Quantitative Trait Loci; QTL) harboring genes that influence variation in dentognathic measures. Four measurements describing each tooth and 32 dental arcade measures will be taken from high quality dental casts of participants of the Jiri Helminth Study, Jiri, Nepal. A maximum-likelihood variance decomposition method for pedigree data implemented in the software program SOLAR is the analytic platform for the analyses. Heritability of each trait will be estimated, and genetic correlations will be examined between all trait pairs. Linkage analysis will identify QTL harboring genes influencing variation in adult dentognathic morphology. The proposed study of the genetic architecture of the dentognathic complex will provide information critical in characterizing the genetic underpinnings of normal dentognathic morphology in humans. PUBLIC HEALTH RELEVANCE: The goal of the proposed study is particularly timely for public health. Deformities of the jaws and teeth are among the most common congenital defects with effects on individuals ranging from minor aesthetic issues associated with malocclusion, to increased risk of caries, to deformities with significant health outcomes such as cleft palate. Identifying the genes responsible for normal variation in morphology of the jaws will provide important information for future gene therapy and tissue engineering treatment regimes.

描述（由申请人提供）：拟议研究的最终目标是发现影响人类牙颌形态变异的基因。这将通过一系列旨在阐明人类牙颌复合体遗传结构基本方面的分析来实现。与牙列和颌骨（牙颌复合体）相关的重大健康问题包括咬合不正导致的美观问题、牙齿拥挤导致的龋齿、嵌塞和感染风险增加，以及严重的先天畸形（例如口颌面裂）。牙颌疾病的病因很复杂。遗传和环境因素均已被确定为影响这些性状变异的因素。拟议的研究旨在检查环境因素（饮食、牙齿护理）相对同质的人群中牙颌特征的正常变化以及之间的关系。我们认为，对遗传和环境因素对牙颌复合体影响的理解必须建立在对正常变异发展的遗传成分的详细了解的坚实基础上。了解遗传对颅骨区域影响的本质对于众多临床医生来说至关重要。随着在修复口面部畸形时将基因治疗和组织工程结合起来变得越来越可能，阐明代表正常形态变异的连续表型的遗传基础的研究至关重要。检查遗传对牙颌复合体正常变异的贡献将有两个具体目标：1）表征描述牙齿和牙弓形态的生物医学相关表型的变异，并探索牙颌形态遗传结构的基本方面。 2) 识别含有影响牙颌测量变异的基因的染色体区域（数量性状基因座；QTL）。描述每颗牙齿的 4 项测量值和 32 项牙廊测量值将从尼泊尔吉日吉日 Helminth 研究参与者的高质量牙模中进行。软件程序 SOLAR 中实现的谱系数据的最大似然方差分解方法是分析的分析平台。将估计每个性状的遗传力，并检查所有性状对之间的遗传相关性。连锁分析将鉴定包含影响成人牙颌形态变异的基因的QTL。对牙颌复合体遗传结构的拟议研究将为表征人类正常牙颌形态的遗传基础提供关键信息。公共卫生相关性：拟议研究的目标对于公共卫生来说特别及时。颌骨和牙齿畸形是最常见的先天性缺陷之一，对个体的影响范围从与咬合不正相关的轻微美学问题到龋齿风险增加，再到具有重大健康后果的畸形（例如腭裂）。识别导致颌骨形态正常变化的基因将为未来的基因治疗和组织工程治疗方案提供重要信息。