The study was undertaken by a team of geneticists based at the University of Jena Hospital (Germany). Specimens for examination were enriched by the service provider ATLAS Biolabs GmbH (Berlin, Germany), and sequence analysis was carried out primarily with Roche’s NimbleGen (Madison, WI, USA) Custom Sequence Capture 385K array.

NimbleGen Sequence Capture arrays are suitable for targeted sequencing of any size, from small target regions such as 250 KB to large regions as large as 30 MB. All human designs utilize the empirically optimized Sequence Capture design algorithm to ensure highly uniform capture. For example, a 250 KB contiguous region, representing a typical GWAS (genome-wide association studies) locus, is captured with high specificity and uniformity. While arrays can be designed to capture specific genomic regions or thousands of exons in parallel, they all incorporate built-in control probes to ensure system performance.

Application of these technologies resulted in the identification of a total of 3858 and 3443 X-chromosomal variants for each of two individuals. Furthermore, a nonsense mutation in the small muscle protein, X-linked (SMPX) of the affected individuals was detected. Nonsense mutations are significant, because they are point mutations in a sequence of DNA that cause a premature stop codon, or a nonsense codon in the transcribed mRNA, resulting in a truncated, incomplete, and usually nonfunctional protein. These results were published in the May 13, 2011, issue of the American Journal of Human Genetics.

Based on their findings, the investigators proposed that long-term maintenance of mechanically stressed inner-ear cells critically depends on SMPX function.

Related Links:
University of Jena Hospital
ATLAS Biolabs GmbH
NimbleGen