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1/250（NCHAM，2004）。这些儿童中超过一半的听力障碍有遗传原因，涉及93个非综合征基因座（货车Camp & Smith，2004）和超过500个综合征基因座（OMIM，2004）。尽管发现了41个非综合征性听力损失的基因，但很少有基因检测被开发出来，这主要是由于为这些基因提供完整的测序测试的巨大成本，这些基因几乎没有已知的常见突变。为了解决这个问题，已经创建了一个耳聋基因芯片，其中包含8个已知与隐性非综合征性听力损失有关的基因：GJB 2，MYO 6，MYO 7A，OTOF，PRES，TMIE，TMPRSS 3和USH 1C。虽然这项技术看起来很有希望成为扩大听力损失基因检测的一种具有成本效益的方法，但它对临床诊断来说是新的，需要以严格的方式进行验证。该项目将确定156名不明原因的语前非综合征型感音神经性听力损失（SNHL）患者，并比较基因芯片技术和传统测序产生的基因序列。这将用于确定碱基识别率、假阳性率和假阴性率，其将反过来用于计算与这些基因的传统双脱氧DNA测序相比，耳聋基因芯片的分析灵敏度以及效率和有效性。此外，来自这156名患者的序列的数据将用于鉴定突变，从而确定该耳聋基因芯片的临床敏感性以及这些基因中的每一个对语前非综合征SNHL的相对贡献。