Enter Note Done


Keywords: Muscular abnormalities; Diagnostics; Characterization of disorders; Genomic structure; Precision medicine

J. Wang; E.T. Lam; A.W.C. Pang; T. Wang; H.B. Sadowski; A.R. Hastie; M. Borodkin

Affiliation: Bionano Genomics, San Diego, California.

Facioscapulohumeral Muscular Dystrophy (FSHD) is one of the most common forms of muscular dystrophy. FSHD symptoms include progressive muscular degeneration, weakness, and atrophy. A genetic disease, FSHD could be inherited and could impact multiple members of a family. Non-inherited FSHD also occurs. Genetic testing is the most reliable way to confirm a diagnosis. Contraction of D4Z4, a tandem repeat region on chromosome 4q35, is diagnostic, when present on a permissive haplotype, for FSHD and can be assayed for by Southern blot.

We have developed a new workflow based on optical mapping on the Bionano Genomics Saphyr platform, which offers several advantages. Based on specific labeling and mapping of ultra-high molecular weight DNA in nanochannel arrays, optical mapping provides a higher resolution determination of D4Z4 and other tandem repeat expansions and contractions, even those which span more than 100 kilobase pairs. Analyses showed that molecules could span and be uniquely mapped to this region, and the repeat region could be accurately sized while also defining permissive and non-permissive alleles (4qA and 4qB). Because of the single-molecule nature of the platform, it is even possible to detect and quantify mosaicism in the repeat length. Also, the data could help resolve borderline or indeterminate Southern blot results. To better define outliers, we have developed a database of typical D4Z4 lengths based on control samples. The data can be imported into a graphical user interface tool for visualization and curation.

Bionano offers sample preparation, DNA imaging and genomic data analysis technologies combined into one streamlined workflow that enables high-throughput analysis of tandem repeat regions of interest. Together, these components allows for efficient analysis of diseases associated with repeat expansion and contraction.