MOLECULAR AND GENETIC ANALYSIS OF THE EEC SYNDROME

描述(改编自调查者摘要)：外胚层 发育不良是指发育异常的疾病。 外胚层组织，主要是头发、皮肤、牙齿和指甲。多种形式的 这种疾病与其他类型的发育障碍一起出现表明 这是它们中常见的基因组改变。一种形式是欧洲经济共同体，涉及个人 有外胚层发育不良、外指趾和腭裂的证据。 该实验室和其他实验室之前的工作已经绘制了一种形式的 人类染色体7q21-22的杂指。几个患有EEC的家庭也 显示这一区域的染色体异常。因此，校长 研究人员提出，人类基因组的这一区域包含有 对这些发育障碍负有责任。YAC/粘粒/噬菌体重叠群 已经开发出7号染色体的这个区域并用来识别 几个候选的EEC基因。在这一应用中，建议研究 通过对染色体的分子分析进一步提炼EEC基因座 7q21-22靶区在散发性和家族性EEC患者中的分布。要完成 为了达到这个目的，研究人员将通过PFGE寻找亚显微缺失 和南方分析。同时，对溶液混合技术进行了研究 捕获将用于从目标区域分离候选的EEC基因。 然后将对患者材料进行突变和表达改变的筛查 以及通过SSCP分析和丢失 一个等位基因的多态mRNA标记表达。最后，耐心 将继续从零星和家族性的欧洲经济共同体中采集样本。 患者支持这些正在进行的研究。这个存储库将被扩展 包括其他多表型障碍，如Rapp-Hodgkin和LAD 其中也包括艾德。然后将确定EEC中的标志物是否 临界区显示与这些其他类型的ED相关 家人。这些拟议的研究提供了一个独特的机会来分离和 描述与几个特征良好的人类有关的基因 发育障碍。此外，对功能的理解， 这些基因最终将允许研究人类基因组的分子基础。 外显性降低和表现力可变，对遗传了解甚少 许多遗传性疾病常见的现象。最后，确定了 与EEC相关的各种出生缺陷之间的关系将 允许对患有这种疾病的个体进行准确的遗传咨询。

DESCRIPTION (Adapted from investigator's Abstract): The ectodermal dysplasias consist of diseases with developmental abnormalities of ectodermal tissue primarily the hair, skin, teeth, and nails. Many forms of this disease present with other types of developmental disorders suggesting a common genomic alteration among them. One form, EEC, involves individuals who show evidence of ectodermal dysplasia, ectrodactyly and cleft palate. Previous work from this laboratory and others have mapped a form of ectrodactyly to human chromosome 7q21-22. Several families with EEC also show chromosomal abnormalities in this region. Thus, the Principal Investigator proposes that this area of the human genome contains the genes responsible for these developmental disorders. A YAC/cosmid/phage contig across this region of chromosome 7 has been developed and used to identify several candidate EEC genes. In this application, studies are proposed to further refine the EEC locus by a molecular analysis of the chromosome 7q21-22 target region in sporadic and familial EEC patients. To accomplish this aim, the investigator will look for submicroscopic deletions by PFGE and Southern analyses. At the same time, the technique of solution hybrid capture will be used to isolate candidate EEC genes from the target region. Patient material will then be screened for mutations and altered expression as well as look for mutations in these genes by SSCP analysis and loss of expression of one allele by polymorphic mRNA markers. Finally, patient samples will continue to be collected from sporadic and familial EEC patients to support these ongoing studies. This repository will be expanded to include other multiple phenotype disorders such as Rapp-Hodgkin and LADD which also include ED. It will then be determined if markers in the EEC critical region demonstrate linkage to these other types of ED-related families. These proposed studies offer a unique opportunity to isolate and characterize genes responsible for several well-characterized human developmental disorders. Furthermore, an understanding of the functions of these genes will eventually allow investigation of the molecular bases of reduced penetrance and variable expressivity, poorly understood genetic phenomena common to many inherited diseases. Finally, the determination of the relationship among the various birth defects associated with EEC will allow accurate genetic counseling to individuals with this disorder.