EXTENDING THE PHENOTYPE OF NON-SYNDROMIC ORAL-FACIAL CLEFTS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究的目的是表征多重CL/P家族和匹配的，以人口为基础的控制，扩大非综合征型CL/P的表型的目的，在一个样本的表型和遗传特征。研究的人口包括三个网站：宾夕法尼亚州西南部，圣路易斯，密苏里州，西弗吉尼亚州。匹兹堡裂宫颅面中心（Pitt）将确定50-75个多重CL/P家庭，总共约370人。此外，将通过圣路易斯儿童医院（圣路易斯）唇腭裂中心确定40-50个多重CL/P家庭，约320人;西弗吉尼亚大学唇腭裂中心（WVU）确定15-20个家庭，约150人。因此，将确定110-155个家庭，总家庭成员约840人。此外，将在每个研究中心确定另外约840名个体的性别和年龄与每个多重家族成员匹配的对照。 每个研究中心的每个参与者将遵循相同的研究方案;简单地说，将对上唇（口轮匝肌）进行超声检查，将评估偏手性，记录皮纹模式，测量面部（用于颅面的电子测量），将通过感知方法评估VPI，并将获得血液样本用于DNA提取。在该项目的四年期间，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，并以一个或多个特征的线性组合进行分析。将探讨的功能的相关结构，将是主成分，如果有显着的多重共线性。分离分析方法将评估每个特征的遗传模式，以及特征的线性组合。将使用连锁分析方法评估每个基因座与每个表型特征（和特征组合）的连锁。将使用参数和非参数方法。此外，方差成分分析将用于许多定量措施，单独和组合。对于具有阳性结果的区域或候选标志物，将使用生物信息学和实验室技术的组合来鉴定和/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.