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A High-Resolution Panel for Uncovering Repeat Expansions that Cause Ataxias

The hereditary ataxias are a group of rare neurological diseases with similar symptoms. Many of these ataxic syndromes are caused by expansions of short tandem repeat (STR) in a number of different genes. Molecular genetic testing to accurately determine the genetic cause of known ataxias is often employed to support clinical diagnoses. We have recently developed an ataxia expansion panel using the PacBio No-Amp targeted sequencing approach to capture and sequence repeat expansion loci associated with fifteen ataxia diseases. The method utilizes CRISPR-Cas9 nuclease and pairs of guide RNAs to excise DNA fragments containing the repeat sequences within ataxia genes. This approach eliminates PCR amplification artifacts, amplification bias, and preserves native DNA for base modification detection. In this study, we sequenced samples with known or unknown diagnosis for ataxia with the No-Amp targeted sequencing panel utilizing PacBio highly accurate long reads – HiFi reads. The high accuracy of HiFi reads provides both certainty in sizing of the repeat expansion and repeat sequence interruption within the expansion sequences. Sequencing results demonstrate the potential of using this repeat expansion panel for eventual genetic testing. As additional ataxia, and related neurological diseases, caused by STR expansions are discovered and studied, the No-Amp targeted sequencing panel could be expanded to include additional targets. The ability to multiplex samples from different patients also makes the method a potentially cost-effective option for molecular genetic screening in the future.

 

Press Release

PacBio Grants Equity Incentive Award to New Employee

Friday, December 3, 2021

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