Evaluation of a Deafness GeneChip

耳聋基因芯片的评估

• 批准号: 6852353
• 负责人: HEIDI L REHM
• 金额: $ 25.95万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6852353
• 关键词: biotechnology; clinical research; computer assisted sequence analysis; computer data analysis; computer program /software; computer system design /evaluation; congenital deafness; gap junctions; genetic screening; human subject; membrane channels; microarray technology; neurogenetics; nucleic acid sequence; patient oriented research; sensorineural hearing loss; technology /technique development

DESCRIPTION (provided by applicant): Hearing loss is the most common sensory impairment with a prevalence of 1 in 250 births (NCHAM, 2004). Over half of these children have a genetic cause for their hearing impairment with 93 nonsyndromic loci (Van Camp & Smith, 2004) and over 500 syndromic loci (OMIM, 2004) implicated. Despite the discovery of 41 of the genes for nonsyndromic hearing loss, very few genetic tests have been developed, largely due to the enormous cost of offering full sequencing tests for these genes with few known common mutations. To address this problem, a Deafness GeneChip has been created which contains 8 genes known to be involved in recessive nonsyndromic hearing loss: GJB2, MYO6, MYO7A, OTOF, PRES, TMIE, TMPRSS3, and USH1C. Although this technology looks promising as a cost-effective way to expand genetic testing for hearing loss, it is new to clinical diagnostics and needs to be validated in a rigorous manner. This project will identify 156 patients with an unknown cause of prelingual nonsyndromic sensorineural hearing loss (SNHL) and compare their gene sequences generated by both GeneChip technology and traditional sequencing. This will be used to determine the base call rate, false positive rate, and false negative rate which will in turn be used to calculate the analytical sensitivity and the efficiency and effectiveness of the Deafness GeneChip, as compared to traditional dideoxy DNA sequencing of these genes. In addition, the data from the sequences of these 156 patients will be used to identify mutations and thereby determine the clinical sensitivity of this Deafness GeneChip and the relative contribution of each of these genes to prelingual nonsyndromic SNHL.

描述（由申请人提供）：听力损失是最常见的感觉障碍，患病率为250分之1（NCHAM，2004年）。这些儿童中有一半以上有93个非综合基因座（Van Camp＆Smith，2004年）和500多个综合基因座（Omim，2004年）的遗传障碍遗传原因。尽管发现了41个用于非综合性听力损失的基因，但很少开发基因检测，这在很大程度上是由于为这些基因提供完整的测序测试的巨大成本，而这些基因很少有已知的常见突变。为了解决这个问题，已经创建了一个耳聋，其中包含已知的8个基因，这些基因涉及隐性的非同步听力损失：GJB2，MyO6，Myo7a，Myo7a，otof，otof，pres，tmie，tmie，tmprss3和ush1c。尽管这项技术看起来很有希望，这是扩大基因测试以促进听力损失的一种经济有效的方式，但它是临床诊断的新方法，需要以严格的方式进行验证。该项目将确定156例未知病因，引起了序言非综合性感觉性听力损失（SNHL），并比较了由Genechip Technology和传统测序产生的基因序列。与这些基因的传统dideoxy DNA测序相比。此外，将使用这156名患者序列的数据来识别突变，从而确定这种耳聋的临床敏感性以及这些基因中每个基因对前后非同步SNHL的相对贡献。