EXTENDING THE PHENOTYPE OF NON-SYNDROMIC ORAL-FACIAL CLEFTS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究的目的是在多个CL/P家族样本和匹配的、基于人群的对照中描述一些表型和遗传特征，目的是扩展非综合征性CL/P的表型。研究对象包括三个地点：宾夕法尼亚州西南部、圣路易斯、密苏里州和西弗吉尼亚州。通过匹兹堡唇腭裂-颅面中心（Pitt）将从50-75个多重CL/P家族中确定约370个个体。此外，将通过圣路易斯儿童医院（圣路易斯）的唇腭裂中心确定40-50个多重唇腭裂家庭，总计约320人；以及来自西弗吉尼亚大学腭裂中心（WVU）的15-20个家庭，总计约150人。因此，将确定110 ~ 155个家庭，共840名家属。此外，将在每个地点为另外大约840个人确定性别和年龄与每个多重家庭成员相匹配的对照。每个站点的每位参与者都将遵循相同的研究方案；简而言之，将对上唇（口轮匝肌）进行超声检查，评估手性，记录皮肤纹模式，测量面部（用于颅相的电子测量），通过感知方法评估VPI，并获取血液样本用于DNA提取。在这个项目的四年时间里，将对至少12个候选基因进行全面研究。每个表型特征，包括CL/P，将单独分析，并在一个或多个特征的线性组合。将探讨特征的相关结构，如果存在显著的多重共线性，将是主成分。分离分析方法将评估每个特征的继承模式，以及特征的线性组合。连锁分析方法将用于评估每个位点与每个表型特征（和特征组合）的联系。参数方法和非参数方法都将被使用。此外，方差成分分析将被用于许多定量测量，单独和组合。对于具有阳性结果的区域或候选标记，将使用生物信息学和实验室技术的组合来识别和/或表征基因。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this study is to characterize a number of phenotypic and genetic features in a sample of multiplex CL/P families and matched, population-based controls with the aim of extending the phenotype of nonsyndromic CL/P. The population under study includes three sites: southwestern Pennsylvania, St. Louis, Missouri, and West Virginia. From 50-75 multiplex CL/P families will be ascertained through the Pittsburgh Cleft Palage-Craniofacial Center (Pitt), about 370 total individuals. In addition, 40-50 multiplex CL/P families will be ascertained through the Cleft Lip/Palate Center of St. Louis Children's Hospital (St. Louis), about 320 total individuals; and 15-20 families from the West Virginia University Cleft Palate Center (WVU), about 150 total individuals. Therefore, 110-155 families with about 840 total family members will be ascertained. In addition, controls matched on gender and age to each multiplex family member will be ascertained at each site for another approximately 840 individuals. Each participant at each site will follow the same research protocol; briefly, an ultrasound will be taken of the upper lip (orbicularis oris), handedness will be assessed dermatoglyphic patterns will be recorded, measurements of the face will be taken (for electronic measurement of the craniofacies), VPI will be assessed by perceptual methods, and blood samples will be obtained for DNA extraction. At least 12 candidate genes will be comprehensively studied during the four years of this project. Each phenotypic feature, including CL/P, will be analyzed separately and in linear combinations of one or more features. The correlational structures of the features will be explored, as will be principal components if there is significant multi-co-linearity. Segregation analysis methods will assess the inheritance patterns for each feature, and for linear combinations of features. Linkage analysis methods will be used to assess linkage with each locus versus each phenotypic feature (and combinations of features). Both parametric and nonparametric approaches will be used. In addition, variance components analyses will be utilized for the many quantitative measures, individually and in combinations. For regions or candidate markers with positive results, a combination of bioinformatic and laboratory techniques will be used to identify and/or characterize genes.