My project focuses on applying new high-throughput genomic sequencing technologies for determination of genetic causes of hearing loss, which has lead to the development of the OtoSCOPEŽ platform. Sanger sequencing was developed in 1977 and is the current gold standard for genetic testing. The primary limiting factors in this method of genetic sequencing are in generating the amplicons via PCR to sequence and the method of sequencing by chain-termination. For example, traditionally, a person diagnosed with autosomal recessive non-syndromic hearing loss (ARNSHL) is initially screened for mutations in GJB2, which may be the cause of hearing loss in 50% of individuals. However, if the deafness-causing mutation are not found in the GJB2 gene, to screen all 28 genes implicated in ARNSHL would require sequence analysis of at least 1000 exons and over 300,000 base pairs. Screening this number of exons in one patient would be expensive (thousands of dollars) and require several weeks for sequencing alone, with significant data analysis by trained individuals also required. Screening for autosomal dominant non-syndromic
hearing loss is similarly time consuming and expensive.
However, new high-throughput sequencing technologies including targeted genomic enrichment and massively parallel sequencing, overcome the limitations of Sanger sequencing, as they can sequence millions or billions of base-pairs simultaneously. Non-syndromic hearing loss is uniquely suited to the use of these new technologies due to the large number of genes involved. We have developed the OtoSCOPEŽ to address the need for comprehensive genetic diagnosis for hearing loss.