Non-invasive Prenatal Diagnosis of Monogenic Disorders by Linked-reads Technology

Description of the presence of cell-free fetal DNA in maternal plasma allowed the possibility of non-invasive prenatal diagnosis. Whereas detection of paternally-inherited alleles is straightforward and being quickly implemented in routine, detection of maternally-inherited alleles remains challenging. To date, the main approach that is being developped, called Relative Haplotype Dosage Analysis, relies on the identification of an allelic imbalance between the mother's wild-type and mutant alleles, relative to the fetal's contribution. This approach therefore requires the study of a propositus to identify the morbid haplotype, which is not always possible in the context of an ongoing pregnancy. In this study, we aim to evaluate the contribution of new technologies, such as linked-read Sequencing, to allow direct identification of parental haplotype in the context of non-invasive prenatal diagnosis.