Whole genome sequencing of fetal cells in maternal blood: advancing non-invasive mutation screening of unborn children

Non-Invasive Prenatal Diagnosis (NIPD) methods are used to diagnose diseases in unborn children without needing invasive procedures, like cutting or puncturing the mother’s womb to obtain cells from the baby, which can lead the loss of the unborn child. Currently, NIPD relies on small fragments of the baby’s DNA (baby’s genetic code) found in the mother's blood to screen for common chromosomal abnormalities, such as Down syndrome. However, a positive diagnosis often requires invasive procedures to confirm it. Also, because the circulating baby’s DNA is broken into small pieces, it is impossible to get a complete picture of the baby’s genetic code and diagnosis of many diseases may be missed. To improve NIPD, we have identified intact cells from the baby in the mother's blood containing the entire and unbroken baby’s DNA. Using novel technologies, I have collected hundreds of cells from the baby in the mother’s blood. We discovered that these include cells from the placenta and cells from the baby’s blood, both carrying the baby's DNA. We have read some of the genes (part of the DNA that specifies proteins) from these cells and now aim to read their complete genomes (entire baby’s DNA) to look for genetic changes that may cause disease. Thus, if awarded this fellowship, I will not only look at the unborn baby’s genes but at all of the information in the baby’s DNA, obtaining the complete genome from the baby’s cells circulating in the mother’s blood. This would allow for unimpeded screening of genetic changes in unborn children, comparable to genetic tests done after birth today. If successful, this could revolutionize prenatal diagnosis, making it accessible to all parents without risk.