ISOLATION OF DISEASE GENES FROM CHROMOSOME 5

从 5 号染色体中分离疾病基因

• 批准号: 2081577
• 负责人: JOHN J WASMUTH
• 金额: $ 17.42万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2081577
• 关键词: autosomal dominant trait; autosomal recessive trait; bone development disorder; chondrodystrophy; chromosome aberrations; craniofacial dysostosis; face; gene mutation; genetic disorder; genetic mapping; genetic markers; human genetic material tag; molecular cloning; northern blottings; nucleic acid sequence

DESCRIPTION: The goals of this application are to clone and analyze the genes for diastrophic dysplasia (DTD) and Treacher Collins syndrome (TCOF1). Both of these genes have been localized to narrow regions of human chromosome 5. The applicants have selected these disease genes because they are located in regions of chromosome 5 for which they have already developed significant mapping tools (radiation hybrid panels and YAC and cosmid contigs). DTD is a very rare autosomal recessive disorder characterized by chondrodysplasia (including short stature and joint dysplasia). However, this condition is more common in Finland (0.8 percent), and the gene has been localized in Finnish families to a 60 kb interval surrounding the gene CSF1R. This region is cloned in YACs, and the applicants propose to develop a cosmid contig across the region, identify the coding regions by exon trapping and cDNA capture, and screen these sequences for mutations specific to DTD. A limited amount of material from a DTD family of Estonian background is available for analysis. TCOF1 is an autosomal dominant disorder. The TCOF1 gene is not as well mapped as DTD, but has now been reduced to a 450 kb interval (from 900 kb at the time of the previous application). The applicants propose to develop additional genetic markers from this region to narrow the localization of TCOF1, and to construct a cosmid contig of this reduced region. Since TCOF1 is an autosomal dominant disorder, the applicants will isolate the chromosome 5's from affected individuals in somatic cell hybrids to facilitate sequencing of candidate genes (by avoiding the need for heterozygote detection). Otherwise, the strategy for the isolation of TCOF1 is very similar to that described for DTD.

描述：此应用程序的目标是克隆和分析 畸形性发育不良（DTD）和Treacher柯林斯综合征的基因 （TCOF1）。这两个基因都定位于狭窄的区域， 人类5号染色体。申请人选择了这些疾病基因 因为它们位于5号染色体的区域， 已经开发了重要的绘图工具（辐射混合面板和 YAC和粘粒重叠群）。 DTD是一种非常罕见的常染色体隐性遗传疾病，其特征是 软骨发育不良（包括身材矮小和关节发育不良）。然而，在这方面， 这种情况在芬兰更为常见（0.8%），而且这种基因 在芬兰的家庭中被定位到一个60 kb的间隔， CSF1R基因。 该区域在YAC中克隆，并且申请人提出 为了开发跨该区域的粘粒重叠群，识别编码 区域，并筛选这些序列 对于DTD特定的突变。来自DTD的有限数量的材料 爱沙尼亚家庭背景可供分析。 TCOF1是一种常染色体显性遗传疾病。TCOF1基因并不是 映射为DTD，但现在已减少到450 kb间隔（从900 在先前应用时为KB）。申请人建议 从这个区域开发额外的遗传标记，以缩小 TCOF1的定位，并构建这种减少的粘粒重叠群 地区由于TCOF1是一种常染色体显性遗传病， 将从受影响的个体中分离出5号染色体， 细胞杂交以促进候选基因的测序（通过避免 杂合子检测的需要）。否则， TCOF1的分离与DTD的分离非常相似。