Genetic Architecture of the Human Dentognathic Complex

人类牙颌复合体的遗传结构

• 批准号: 7845555
• 负责人: Richard J Sherwood
• 金额: $ 66.97万
• 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/7845555
• 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; public health relevance; 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stagnathic形态变异的基因。这将通过一系列旨在阐明人类齿齿复合物遗传结构的基本方面的分析来实现。与牙齿和下巴有关的重大健康问题（牙科综合体）范围从因咬合不良引起的美学问题，到增加龋齿，撞击和因牙齿拥挤而引起的感染的风险，再到明显的先天性畸形（例如，口腔分离）。牙科疾病的病因很复杂。遗传和环境因素都被确定为影响这些特征变化的因素。拟议的研究旨在检查环境因素（饮食，牙科护理）相对均匀的人群中的齿状特征的正常差异和关系。我们认为，对遗传因素和环境因素对牙科复合物的影响的理解必须基于对正常变异发展的遗传成分的详细知识的坚实基础。了解遗传影响对颅骨区域的性质对于各种临床医生至关重要。随着在接近口面畸形的修复时，越来越有可能纳入基因治疗和组织工程，因此阐明了阐述了典型的正常形态变化的连续表型的遗传基础的研究至关重要。在两个具体目的中将解决对牙科复合物正常变异的遗传贡献的检查：1）描述了描述牙齿和牙齿术形态的生物医学相关的表型的变化，并探索了牙科形态的遗传结构的基本方面。 2）识别植物区域（定量性状基因座； QTL）具有影响牙科措施变异的基因。描述每颗牙齿和32个牙齿街机措施的四个测量值将从尼泊尔Jiri研究的Jiri Helminth研究的参与者的高质量牙齿铸件中进行。在软件程序太阳能中实现的谱系数据的最大可能的差异分解方法是分析的分析平台。将估算每个性状的遗传力，并将检查所有性状对之间的遗传相关性。链接分析将确定具有影响成人牙科形态变异的基因的QTL。对牙科复合物的遗传结构的拟议研究将为表征人类正常齿状形态的遗传基础至关重要。公共卫生相关性：拟议研究的目标特别适合公共卫生。颌骨和牙齿的畸形是最常见的先天性缺陷之一，对从与不良批判性相关的次要美学问题到龋齿的风险增加，到具有明显健康结果（例如left裂的畸形）的人的影响。确定颌骨形态正常差异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。