Development and clinical application of universal haplotype-based non-invasive prenatal diagnosis for single gene disorders

Abstract

Non-invasive prenatal diagnosis (NIPD) is an important alternative to standard genetic testing which relies on invasive sampling techniques, such as amniocentesis or CVS, with associated miscarriage risks. The NIPD approach examines the small amount of free foetal DNA present in the maternal blood during pregnancy and therefore avoids the risk of miscarriage.

Our department was funded by the Health Innovation Challenge Fund (HICF) in 2013-2016 to develop NIPD for single gene disorders including spinal muscular atrophy (SMA) and Duchenne and Becker Muscular dystrophy (DMD/BMD). Our centre was the first to offer NIPD for these disorders and our service continues to offer testing internationally. Our current technique, relative haplotype dosage (RHDO), can potentially be applied to most rare genetic diseases, however we are only currently able to offer testing to couples with a previous affected child. This prevents some patients from accessing our service. In order to increase access to testing we need to develop a universal phasing system so families without a reference sample from an affected family member can be tested.

This research aims to evaluate the use of available technologies for universal phasing in non-invasive prenatal diagnosis of Single Gene Disorders. The subsequent aim of the project is to validate and implement the chosen methodology into our diagnostic clinical laboratory service.