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官损伤，发病率为每250名新生儿中就有一名(NCHAM，2004)。这些儿童中有超过一半的人有遗传因素导致他们的听力障碍，其中93个非综合征基因座(Van Camp&Smith，2004)和500多个综合征基因座(OMIM，2004)被牵连。尽管已经发现了41个非综合征性听力损失的基因，但很少有基因测试被开发出来，这在很大程度上是因为为这些几乎没有已知常见突变的基因提供全序列测试的巨大成本。为了解决这个问题，一种耳聋基因芯片被创造出来，它包含8个已知与隐性非综合征性听力损失有关的基因：GJB2、MYO6、MYO7A、OTOF、PRES、TMIE、TMPRSS3和USH1C。虽然这项技术看起来是一种经济高效的方法来扩大听力损失的基因测试，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名原因不明的语前非综合征性感音神经性耳聋(SNHL)患者，并比较他们通过基因芯片技术和传统测序产生的基因序列。这将被用来确定基本呼叫率、假阳性率和假阴性率，这些假阴性率将被用来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和效率和有效性。此外，来自这156名患者的序列数据将被用来识别突变，从而确定这种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。