FUNCTIONAL GENOMICS OF A DEAFNESS/BLINDNESS SYNDROME

耳聋/失明综合征的功能基因组学

• 批准号: 6176184
• 负责人: THOMAS B. SHOWS
• 金额: $ 21.82万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6176184
• 关键词: animal genetic material tag; blindness; complementary DNA; congenital deafness; developmental genetics; embryo /fetus tissue /cell culture; gene induction /repression; gene mutation; genetic disorder; genetic transcription; human fetus tissue; human genetic material tag; laboratory mouse; molecular cloning; neurogenetics; nucleic acid sequence; retinitis pigmentosa; transcription factor

DESCRIPTION: The gene responsible for Usher Syndrome Type 1C, an autosomal recessively inherited deafness/blindness syndrome, was previously mapped by genetic linkage analysis between the markers D11S861 and 899. The major focus of this proposal is to clone, and characterize the USH1C gene and its product, providing critical information on the underlying pathophysiological mechanism for this and other forms of dual neurosensory syndromes. Since this region was found to be refractory to cloning using YAC (yeast artificial chromosome) based vectors, a P1-artificial -chromosome (PAC) contig was constructed. The 400 kb contig encompassing the critical region is providing the genomic resources for a gene hunt using exon trapping, cDNA selection, and direct sequencing. We are currently investigating several new transcription units which we have identified and mapped into the critical region. The current proposal is directed at (1) identifying transcription units in the critical region; (2) analyzing cDNAs to determine which represent intriguing candidate genes; (3) examining patient DNA for mutations by sequencing to identify the gene, and; (4) characterizing the gene and its product at the tissue and cellular levels. Since the phenotype for Usher type 1C is indistinguishable with the other five USH1 loci, this study may yield insights into the mechanism responsible for profound deafness, vestibular dysfunction and progressive retinal degeneration and provide new insights into the syndrome responsible for the majority of children born with dual neurosensory degeneration.

描述：负责Usher综合征1C的基因，常染色体 隐性遗传聋/失明综合征，以前是由 标记D11S861和899之间的遗传连锁分析。 该提议的重点是克隆，并表征USH1C基因及其它 产品，提供有关基础病理生理学的关键信息 这种和其他形式的双重神经感觉综合征的机制。 自从 发现该区域使用YAC（酵母 人造染色体）基于P1人造 - 染色体（PAC）的载体 构造了对。 包含关键区域的400 kb重叠群 正在使用外显子捕获，cDNA提供基因组狩猎的基因组资源 选择和直接测序。 我们目前正在调查几个 我们已经确定并映射到的新转录单元 关键区域。 当前的建议针对（1）识别 关键区域的转录单元； （2）分析cDNA以确定 代表着有趣的候选基因； （3）检查患者DNA的 通过测序识别基因的突变，以及； （4）表征 基因及其产物在组织和细胞水平上。 由于表型 对于Usher 1C类型，与其他五个USH1基因座无法区分 研究可能会深入了解导致深刻的机制 耳聋，前庭功能障碍和进行性视网膜变性和 对负责大多数的综合症提供新的见解 患有双重神经感觉变性的孩子。

项目成果

Mapping of genes and transcribed sequences in a gene rich 400-kb region on human chromosome 11p15.1-->p14.

人类染色体 11p15.1-->p14 上基因丰富的 400 kb 区域中的基因和转录序列的定位。

• DOI: 10.1159/000056877
• 发表时间: 2001
• 期刊: Cytogenetics and cell genetics
• 作者: Caldwell,GM;Eddy,RL;Day,CD;Haley,LH;Cooper,PR;Sait,SS;Hejtmancik,F;Smith,RJ;Morton,CC;Higgins,MJ;Shows,TB
• 通讯作者: Shows,TB