PHENOTYPE AND GENETICS IN OROFACIAL CLEFT FAMILIES

口面裂，唇腭裂（CLIP），健康问题，影响全世界每500-1000名新生儿中的一名。我们小组和其他人在鉴定CL/P的遗传位点方面取得了重大进展，证实了CL/P遗传病因学的可疑复杂性。 特征归因于每个基因，以便将新兴的研究结果转化为临床实践。与CLIP相关的表型特征也取得了进展：有证据表明，发育不对称效应可能有助于CLIP的病因，并且在明显未受影响的唇腭裂患者亲属中可能存在未被识别的亚临床表型。 本研究的主要目的是利用扩大的表型谱CLIP在我们的连锁和关联研究的候选基因，基因组扫描和精细定位标记。扩大CLIP的表型谱将更准确地识别在特定裂家庭中在遗传水平上分离的表型，从而增加我们的基因定位和关联研究的能力。此外，如果我们能够识别出可能携带裂缝基因的未受影响（即非裂缝）个体（例如具有亚临床表型表达的个体），那么这种常见出生缺陷的复发风险计算和遗传咨询将得到极大改善。因此，我们将研究表型特征， 在世界范围内的几个人群中，通过CL/P个体加上对照确定多重激酶（即2个或更多受影响者）。将被调查的具体特征包括：惯用手，颅面测量，不对称（基于皮纹模式和颅面测量），咽喉能力（通过感知筛选）和口轮匝肌的解剖结构。将分析每个单独的特征，以及由两个或多个特征组成的复合性状。候选基因将与其他中心项目合作进行优先排序;候选基因将使用基因型核心进行基因分型。基因组扫描标记已经可用于大多数这些家庭。所有 标记将用于CLIP和多重激酶中每个表型特征的连锁和关联研究，并且还将包括在寻找促成风险的基因之间的相互作用的分析中。

Orofacial clefts, cleft with without cleft (CLIP), health problem, affecting one in every 500-1000 births worldwide. There has been substantial recent progress by our group and others in identifying genetic loci for CL/P, confirming the suspected complexity in the genetic etiology of CL/P. As the genetic factors contributing to CLIP emerge, it is essential to identify the phenotypic characteristics attributable to each gene n order to translate the emerg ng research results into cinical practice. Progress has also been made regarding phenotypic features associated with CLIP: there is evidence that developmental asymmetry effects may contribute to the etiology of CLIP, and that there may be unrecognized sub-clinical phenotypes in apparently unaffected relatives of individuals with clefts. The primary goal of this study is to utilize an expanded phenotypic spectrum for CLIP in our linkage and association studies of candidate genes, genome-scan and fine-mapping markers. An expanded phenotypic spectrum for CLIP will more accurately identify the phenotype that is segregating at a genetic level in specific cleft families, thereby increasing the power of our gene mapping and association studies. Furthermore, if we can then identify unaffected (i.e. non-cleft) individuals who are likely to be carrying cleft genes (e.g. individuals with sub-clinical phenotypic expression), then recurrence risk calculations and genetic counseling for this common birth defect will be vastly improved. Therefore, we will investigate phenotypic features in multiplex kindreds (i.e. with 2 or more affecteds) ascertained through CL/P individuals, plus controls, in several populations world-wide. The specific features that will be investigated include: handedness, craniofacial measurements, asymmetry (based on dermatoglyphic patterns and craniofacial measurements), velopharyngeal competence (by perceptual screening) and anatomy of the orbicularis oris muscle. Each individual feature will be analyzed, as well as composite traits composed of two or more features. Candidate genes will be prioritized in collaboration with the other Center Projects; candidate genes will be genotyped utilizing the Genotype Core. Genome-scan markers are already available for most of these families. All markers will be used for linkage and association studies of CLIP and each phenotypic feature in the multiplex kindreds, and will also be included in analyses looking for interactions between genes contributing to risk.