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.
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| Teekakirikul, Polakit; Cox, Stephanie; Funke, Birgit et al. (2011) Targeted sequencing using Affymetrix CustomSeq Arrays. Curr Protoc Hum Genet Chapter 7:Unit7.18 |
| Gowrisankar, Sivakumar; Lerner-Ellis, Jordan P; Cox, Stephanie et al. (2010) Evaluation of second-generation sequencing of 19 dilated cardiomyopathy genes for clinical applications. J Mol Diagn 12:818-27 |
| Kothiyal, Prachi; Cox, Stephanie; Ebert, Jonathan et al. (2010) High-throughput detection of mutations responsible for childhood hearing loss using resequencing microarrays. BMC Biotechnol 10:10 |
| Zimmerman, Rebekah S; Cox, Stephanie; Lakdawala, Neal K et al. (2010) A novel custom resequencing array for dilated cardiomyopathy. Genet Med 12:268-78 |
| Kothiyal, Prachi; Cox, Stephanie; Ebert, Jonathan et al. (2009) An overview of custom array sequencing. Curr Protoc Hum Genet Chapter 7:Unit 7.17 |
