HYPOHIDROTIC ECTODERMAL DYSPLASIA GENE

拟议的研究是正在进行的合作努力的一部分， 分离并鉴定X连锁少汗性外胚层发育不良 (EDA)基因EDA，一种X连锁疾病，其特征是先天性 没有头发，牙齿和外分泌汗腺，被假设为 由于上皮-间充质相互作用的缺陷， 形态发生EDA基因及其突变的鉴定 它对诊断和咨询具有医学意义， 患有EDA的家庭，最常见的外胚层发育不良形式。其 表征将有助于我们理解生物学 机制和途径，在很大程度上是未知的，涉及上皮- 间充质相互作用在分化过程中， 表皮和口腔外胚层。该项目的目标是隔离 EDA基因座的候选基因，通过定位的方法， 该疾病已被定位到X染色体的200-300 kb区域， 染色体（Xq13.1），并从EDA中分离基因组克隆 通过分析先前确定的患者的关键区域 分子重排将筛选这些克隆的表达 序列，并用于从cDNA文库中分离候选基因。的 候选基因将被测试，以证明它是真正的EDA基因， 通过筛选>130个不相关的突变来鉴定其中的突变 受影响的个人。详细分析了 然后进行EDA基因内的突变。

The proposed research is part of an on-going collaborative effort to isolate and characterize the X-linked hypohidrotic ectodermal dysplasia (EDA) gene. EDA, an X linked disorder characterized by the congenital absence of hair, teeth, and eccrine sweat glands, is hypothesized to be due to a defect in epithelial-mesenchymal interactions during morphogenesis. Identification of the EDA gene and the mutations within it are of medical significance for the diagnosis and counseling of families with EDA, the most common form of ectodermal dysplasia. Its characterization will assist in our understanding of the biologic mechanisms and pathways, largely unknown, involved in epithelial- mesenchymal reciprocal interactions during differentiation of the epidermal and oral ectoderm. The goal of the project is to isolate candidates genes for the EDA locus by the method of positional cloning.The disorder has been mapped to a 200-300 kb region of the X chromosome (Xq13.1), and genomic clones will be isolated from the EDA critical region by an analysis of patients previously identified with molecular rearrangements. These clones will be screened for expressed sequences, and used to isolate candidate genes from cDNA libraries. The candidate gene will be tested to prove it is truly the EDA gene by the identification of mutations within it by screening >130 unrelated affected individuals. A detailed analysis of the nature and site of mutations within the EDA gene will then be undertaken.