Genetic Architecture of the Human Dentognathic Complex

人类牙颌复合体的遗传结构

• 批准号: 8233523
• 负责人: Richard J Sherwood
• 金额: $ 69.35万
• 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 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8233523
• 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

ABSTRACT 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.

抽象的 拟议研究的最终目标是发现影响人类变异的基因 牙科形态。这将通过一系列旨在阐明的分析来完成 人类挖掘综合体的遗传结构的基本方面。 与牙齿和下巴有关的重大健康问题（牙科综合体）范围从 审美问题由于错牙合，以增加龋齿，撞击和感染的风险 拥挤，明显的先天性畸形（例如，口面裂）。牙科疾病的病因 很复杂。遗传和环境因素都被确定为影响变异的因素 这些特征。拟议的研究旨在检查正常的变化，以及之间的关系 在环境因素（饮食，牙齿护理）相对均匀的人群中，齿状特征。 我们认为，了解影响遗传和环境因素对影响的影响 牙科复合物必须基于对遗传成分的详细知识的坚实基础 正常变异的发展。 了解遗传影响对颅骨区域的性质对于某人至关重要 各种各样的临床医生。随着纳入基因治疗和组织的越来越有可能 在接近口面畸形学修复时进行工程学，研究阐明了遗传 代表正常形态变化的连续表型的基础是至关重要的。 检查遗传贡献对牙科疾病复合物正常变异的贡献将得到解决 在两个具体目的中：1）表征描述牙齿和牙齿的生物医学相关的表型的变化 街道形态和探索牙科形态遗传结构的基本方面。 2）识别植物区域（定量性状基因座； QTL），该染色体具有影响变异的基因 牙科措施。 四个描述每颗牙齿和32个牙齿街机措施的测量值将从高中采取 尼泊尔JIRI的JIRI Helminth研究参与者的质量牙科演员。最大似然差异 软件程序太阳能实现的谱系数据的分解方法是分析平台 用于分析。将估算每个性状的遗传力，并将检查遗传相关性 所有特征对。链接分析将识别QTL具有影响成人牙科变异的基因的QTL 形态学。提出的对牙科综合体遗传结构的研究将提供 表征人类正常牙科形态的遗传基础的信息至关重要。