GENETIC ETIOLOGY OF NONSYNOMIC CLEFT PALATE

唇裂和腭裂是常见的出生缺陷，影响1-2/1000活产。很明显，遗传因素对其病因有重要影响。大多数口面裂是非综合征的孤立性效应，可分为两种不同的表型：（1）唇腭裂（CL/P）和（2）单纯腭裂（CPO）。两者都是遗传上复杂的性状，这限制了识别疾病位点或基因的能力。以前的影响，以确定非综合征裂缝的遗传病因依赖于候选基因的方法，大多数研究集中在CL/P。本项目和未来的项目的总体目标是确定疾病位点和基因参与非综合征CPO采用新的连锁策略，研究受影响的亲属对和扩展家系。这些方法，尚未被应用于CPO，是非常强大的，因为不需要有关的生物过程或遗传模式的先验知识。该项目的具体目标是确定来自中国上海地区的150个多成员患有CPO的家庭。另外100名CPO患者将与其父母一起沿着确定用于连锁不平衡分析。这项工作将与上海闸北眼科医院的刘友娥医生和匹兹堡腭裂中心的玛丽马拉齐塔医生合作进行，他们自匹兹堡大学腭裂-颅面中心的腭裂诊所以来一直合作，通过合作研究者的努力，已经招募了45个家庭。该项目的范围将是评估候选基因的CPO使用连锁和连锁不平衡分析。中国上海的人群相对同质，这一独特的品质增加了绘制疾病位点的能力，也促进了向物理作图和基因鉴定的过渡。本研究的优势在于可以在多个位点确定相对大量的受影响的亲属对，从而增加了本研究检测即使是中等影响的基因座的总体功效。它将通过这样的项目，其中与世界各地的研究人员建立合作，应用遗传策略的组合，将确定慢性阻塞性肺病的疾病位点。最终，这将进一步了解正常和异常的颅面发育，从而可以开发预防CPO的治疗方法。

Cleft lip and cleft palate are common birth defects affecting 1-2/1000 live births. It is apparent that genetic factors contribute significantly to their etiology. Most orofacial clefts are non- syndromic, isolated effects, which can be separated into two different phenotypes: (1) cleft lip with or without cleft palate (CL/P) and 2) cleft palate only (CPO). Both are genetically complex traits, which has limited the ability to identify disease loci or genes. Previous effects to determine the genetic etiology for non-syndromic clefts have relied on candidate gene approaches with most studies focused on CL/P. The overall objective of this and future projects is to identify disease loci and genes involved in non-syndromic CPO by employing new linkage strategies to study affected relative pairs and extended pedigrees. These approaches, which have yet been applied to CPO, are very powerful in that no prior knowledge about the involved biological processes or inheritance pattern is needed. The specific aim of this project is to ascertain 150 families with multiple members affected with CPO from the Shanghai region of China. An additional 100 CPO patients will be ascertained along with their parents for use in linkage disequilibrium analyses. This will be performed in collaboration with Dr. You-e Liu of the Zhabei Eye Hospital, Shanghai and Dr. Mary Marazita of the Cleft Palate Center, Pittsburgh, who have collaborated since Cleft Palate Clinic at the University of Pittsburgh Cleft Palate-Craniofacial Center to add to the 45 families already recruited through the efforts of there collaborative investigators. The scope of this project will be to evaluate candidate genes for CPO using both linkage and linkage disequilibrium analyses. The population of Shanghai, China is relatively homogeneous, which a unique quality that increases the power to map a disease loci and also facilitate the transition to physical mapping and gene identification. The strength of this study is the relatively large numbers of affected relative pairs that can be ascertained at multiple sites, thus increasing the overall power for the study to detect loci of even modest effect. It will be through projects such as this one, in which collaborations with researchers world wide have been established to apply a combination of genetic strategies, that disease loci for CPO will be identified. Ultimately, this will further the knowledge of normal and abnormal craniofacial development, such that therapies to prevent CPO can be developed.