F. Sessions Cole, MD; Jennifer Wambach, MD; Dustin Baldridge, MD; Dan Wegner
GENOMICS OF BIRTH DEFECTS In 2014, CDI funding enabled a collaboration between Washington University School of Medicine experts in newborn medicine, genetics, genomics, pediatric cardiology, critical care medicine, computational biology and developmental biology. Their focus has been to identify genetic problems in babies and young children who otherwise would not have a diagnosis. “Once we confirm a birth defect of currently unknown origin and enroll the family in our study, we collect the DNA from the affected baby, siblings and both parents. Then we look across the entire genome to see if we can identify the gene code anomaly that has caused the problem,” says co-principal investigator and the Park J. White, MD, Professor of Pediatrics, F. Sessions Cole, MD. The study also involves, on a day-to-day basis, co-principal investigator Jennifer Wambach, MD, newborn medicine; Dustin Baldridge, MD, newborn medicine; and Dan Wegner, laboratory manager. It sounds fairly straightforward, but Dr. Cole says because all humans carry millions of gene code differences, trying to sort through them to find which one created the defect can seem like an insurmountable challenge. In fact, it takes the high level of computational firepower at the McDonnell Genome Institute at Washington University to make that type of needle-in-a-haystack work possible.
The Genomics of Birth Defects project has enrolled more than 100 infants and children with structural birth defects, along with their families. So far, the study has provided diagnoses for around 25 percent of these families. Most of these infants and children have birth defects involving a single organ system, such as the heart, lung or brain, but 30 percent have birth defects involving multiple organ systems. “We are one of the first research projects in the country using whole genome sequencing — a deep dive into more than three billion DNA base pairs —as opposed to exome sequencing, which only looks at the genetic code inside genes,” says Dr. Baldridge, who has been able to pursue a research career in genetics with the CDI funding of this project. “That means we’ve been able to expand our search of gene code problems from one percent to 100 percent of the base pairs that make up the human genome.” Once a candidate gene code problem is identified, the team turns to a model system, such as mice or zebrafish, to confirm that it is what has caused the defect. “The CDI has allowed us to build a bridge between patients in the genetics clinic, the McDonnell Genome Institute and basic science investigators throughout the School of Medicine to help families solve their medical mysteries,” Dr. Baldridge says.
PROTECTING OUR MOST VULNERABLE The Genetics Of Birth Defects