Massively parallel sequencing as a molecular diagnostic tool

Abstract

My research focuses on the development of strategies to deliver non-invasive prenatal diagnosis of fetal genetic diseases through the analysis of circulating fetal DNA. However, circulating fetal DNA analysis poses a number of technical challenges. We recently showed that massively parallel sequencing is an ideal tool for the analysis of challenging molecular targets like circulating fetal DNA. We showed that massively parallel sequencing is sensitive to the detection of low-abundance targets even in the short fragmented form as in the case of circulating fetal DNA. Sequencing can specifically determine the genetic identity of the sequenced DNA molecules while simultaneously offers precise quantification of the relative amounts of DNA targets in the sample. We reported a strategy for assembling the fetal genome by maternal plasma DNA sequencing and developed an approach for determining fetal inheritance of both paternally-inherited and maternally-inherited genes. The cost-effectiveness of sequencing could be enhanced by using targeted approaches. We further showed that sequencing could be used to study the size profiles of fetal DNA and DNA molecules in plasma of transplantation recipients. We believe that massively parallel plasma DNA sequencing would lead to a paradigm shift in molecular diagnostics.