Statistical Genetic Analysis of Complex Craniofacial and Dental Genetic Disorders

当前提案寻求激活K99/R 00合同（1 K99 DE 018085）的ROO阶段。Pl博士 Manika Govil是匹兹堡大学牙科医学中心的统计遗传学家， 颅面和牙齿遗传学。她已经完成了K99阶段的职业发展目标 并且准备好移动到ROO阶段中的独立位置。机构支持和环境 对少年派的成就起到了重要作用Pi工作的K99阶段的目标是获得 颅面和牙齿遗传性疾病的基本知识，特别强调理解 CL/P的病因学、流行病学和表型。 遗传特性对于开发具有计算上可行的实现的方法至关重要， 能够对数据中预期的异质性进行建模，以识别多基因原因。她的长期 目标是成为一个独立的，跨学科的研究科学家与资助的研究计划， 将汇集统计和计算机科学方面的专业知识，以促进我们对复杂事物的理解 比如颅面和牙齿遗传疾病为了实现这些目标。戈维尔博士已经完成了 在玛丽·马拉齐塔和维罗妮卡·维兰德博士的资助下，在她的K99阶段。Marazita医生是 几个颅面和牙齿遗传赠款，并在口面研究的专业知识。Viejand博士是PI 关于复杂性状方法开发的赠款，以及复杂性状分析的赠款， 像自闭症和CL/P 实验的重点ofthis建议是对发展和实施的计算 可行的统计遗传方法，特别是后验连锁概率（PPL）的扩展， 无模型似然基类方法;这些方法与其他现有统计方法的比较 方法，以及它们在分析复杂颅面和牙齿遗传性疾病，如 唇裂伴或不伴腭裂和口腔健康差异。

The current proposal seeks activation ofthe ROO phase of a K99/R00 award (1K99DE018085). The Pl, Dr. Manika Govil, is a statistical geneticist at the University of Pittsburgh School of Dental Medicine's Center for Craniofacial and Dental Genetics. She has fulfilled the career development aims planned for the K99 phase and is ready to move to an independent position in the ROO phase. The institutional support and environment have been instrumental for the Pi's achievements. A goal of the K99 phase of the Pi's work was to gain fundamental knowledge of craniofacial and dental genetic disorders, with special emphasis on understanding the etiology, epidemiology, and phenotypes of CL/P. A deeper understanding of CL/P and other complex genetic traits is critical to the development of methods with computationally feasible implementations that will be capable of modeling the expected heterogeneity in the data to identify multigenic causes. Her long-term goal is to become an independent, interdisciplinary research scientist with a funded research program that will bring together expertise in statistics and computer science to advance our understanding of complex traits like craniofacial and dental genetic disorders. To achieve these goals. Dr. Govil has completed training under Drs. Mary Marazita and Veronica Vieland during the K99-phase of her grant. Dr. Marazita is the PI on several craniofacial and dental genetic grants, and has expertise in orofacial research. Dr. Viejand is the PI on grants relating to methods development for complex traits, as well as grants for the analysis of complex traits like autism and CL/P. The experimental focus ofthis proposal is on the development and implementation of computationally feasible statistical genetic methods, in particular, extensions to the posterior probability of linkage (PPL), a model-free likelihood-based class of methods; comparison ofthese methods to other existing statistical approaches, and their application to the analysis of complex craniofacial and dental genetic disorders like cleft lip with or without cleft palate and oral health disparity.