HYPOHIDROTIC ECTODERMAL DYSPLASIA--GENETIC ANALYSIS

少汗性外胚层发育不良--遗传分析

• 批准号: 2132555
• 负责人: JONATHAN ZONANA
• 金额: $ 18.58万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2132555
• 关键词: autosomal dominant trait; autosomal recessive trait; developmental genetics; disease /disorder classification; ectoderm; endonuclease; gene mutation; gene rearrangement; genetic disorder; genetic disorder diagnosis; genetic mapping; genetic markers; genetic polymorphism; histogenesis; human genetic material tag; human population genetics; human subject; hyperplasia; linkage mapping; molecular cloning; molecular genetics; molecular pathology; nucleic acid hybridization; nucleic acid probes; phenotype; prenatal diagnosis; pulsed field gel electrophoresis; radiotracer; restriction fragment length polymorphism; sex linked trait; skin hyperplasia; southern blotting

DESCRIPTION (Adapted from the applicant's abstract): The EDs are a heterogeneous collection of disorders of unknown pathogenesis. The need to develop new molecular approaches to their analysis has been noted, and the investigators believe that molecular genetic studies, specifically linkage analysis, will improve their classification, produce new diagnostic tools, and ultimately lead to identification of their molecular defects and to an understanding of the process of normal morphogenesis. The investigators propose to study two prototypic disorders, XLHED, the commonest of the EDs, and the Clouston syndrome, an hidrotic form of ED which is inherited as an autosomal dominant trait. For XLHED: The investigators will perform fine genetic mapping studies of the disorder, localized to Xp11.1-Xq21.1 region, to define the order of closely linked polymorphic marker loci in relation to the disease locus. The identification of close flanking markers is essential for both accurate diagnostic applications, and for the physical mapping and cloning of the XLHED locus. To this end, the investigators will screen for highly polymorphic (heterozygosity >70 percent) microsatellite DNA markers in the pericentromeric region of the X-chromosome. The investigators will utilize these markers to address the question of the existence and frequency of a proposed clinically indistinguishable autosomal recessive form of the disorder, which if unrecognized could cause serious diagnostic errors. In addition, a large number of unrelated males will be screened, initially with anonymous DNA probes, but ultimately with expressed and conserved sequences from the region, to identify sub-microscopic deletions involving the XLHED locus. For the Clouston syndrome: Its position on the human gene map, presently unknown, will be localized by the linkage analysis of two very large kindreds, utilizing a series of highly polymorphic loci (RFLPs and microsatellites) distributed over all autosomes (exclusion mapping). Potential candidate genes or chromosomal regions will be given priority. Once linkage is established, fine mapping will be performed, to lay the groundwork for subsequent physical mapping around the disease locus, and cloning of the gene.

描述（改编自申请人摘要）：ED是一种 病因不明的异质性疾病集合。 需要 开发新的分子方法来分析它们已经注意到， 研究人员认为，分子遗传学研究，特别是连锁， 分析，将改善其分类，产生新的诊断工具， 并最终导致其分子缺陷的鉴定， 了解正常形态发生的过程。 调查人员 建议研究两种典型的疾病，XLHED，最常见的ED， 和Clouston综合征，一种艾德的多汗形式， 常染色体显性性状 对于XLHED：研究者将进行精细的遗传图谱研究， 这种无序定位于Xp11.1-Xq21.1区域，以定义 与疾病位点密切相关的多态性标记位点。 近侧翼标记的鉴定对于精确的 诊断应用程序，以及物理映射和克隆 XLHED基因座。 为此，调查人员将筛选高度 多态性（杂合性> 70%）微卫星DNA标记， X染色体的着丝粒周围区域。 调查人员将利用 这些标志，以解决的存在和频率的问题， 提出临床上难以区分的常染色体隐性形式的 疾病，如果不被识别，可能会导致严重的诊断错误。 在 此外，最初将筛选大量无关的男性， 用匿名的DNA探针，但最终表达和保守的 从该区域的序列，以确定亚显微缺失， XLHED基因座。 对于Clouston综合征：它在人类基因图谱上的位置，目前 未知的，将是本地化的连锁分析两个非常大的 利用一系列高度多态性的基因座（RFLPs和 微卫星）分布在所有常染色体上（排除作图）。 潜在的候选基因或染色体区域将被优先考虑。 一旦建立了联系，将进行精细测绘， 为随后围绕疾病位点的物理绘图奠定基础，以及 基因的克隆。