IGF::OT::IGF HIGH THROUGHPUT GENOTYPING AND DNA SEQUENCING FOR STUDYING THE GENETIC CONTRIBUTIONS TO HUMAN HEALTH AND DISEASE

唇裂或不伴有腭裂（CL/P）或仅腭裂（CPO）的非综合征性口面裂（OFCs）构成了人类出生缺陷的很大一部分（全球约1/700活产），需要手术、营养、牙科、语言、医疗和行为干预，从而造成了巨大的公共卫生、经济和个人负担。在该项目之前的资助期内，我们实现了所有既定目标，并明确建立了我们的研究小组在过去十年中开发的丰富的表型范式。我们的表型方案可以帮助定义导致OFCs的机制，并更准确地预测这些缺陷的个体风险。分布在受影响家庭中的OFC的亚临床表现（例如，细微的言语异常）可以揭示病因的线索。许多基因/基因座现在已经被确定为显性OFC，主要基于当前资助期产生的全基因组关联研究。

: Nonsyndromic orofacial clefts (OFCs) of the lip with or without cleft palate (CL/P) or of the palate only (CPO) comprise a significant proportion of human birth defects (about 1/700 live births worldwide) requiring surgical, nutritional, dental, speech, medical and behavioral interventions and thus impose substantial public health, economic, and personal burdens. During the previous funding periods of this project, we achieved all our delineated goals and unequivocally established a rich phenotyping paradigm that our research group has developed over the last decade. Our phenotyping protocol can help define mechanisms that lead to OFCs and more precisely predict individual risks for these defects. Subclinical expressions of OFC (e.g., subtle speech abnormalities) that are distributed within affected families can reveal clues about etiology. Numerous genes/loci have now been identified for overt OFC, based largely on genome-wide association studies resulting from the current funding period.