Research Roundup: September 21, 2018

Welcome to the September 21, 2018 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Thank you for asking, but….

The NIH-funded BabySeq project is the first randomized, controlled clinical trial of genetic sequencing in both healthy and sick newborns. In Genetics in Medicine, project leaders Casie Genetti (Boston Children’s Hospital), Richard Parad (Brigham and Women’s Hospital, BWH), Broad associate member Alan Beggs, and associate member Robert Green in the Broad’s Program in Medical and Population Genetics (MPG) reveal why only 268 of the first 3,800 families approached to participate ended up enrolling in the study. The reasons had less to do with genetics or privacy concerns than with a low interest in research in general, in addition to challenges of participating in research after the birth of a child. Read more from BWH, GenomeWeb, or WBUR’s CommonHealth.

Solving a TP53 mystery

Tumor protein p53 (TP53) is the most frequently mutated gene in human cancer, and while mutations have been documented at more than 1,100 sites within the gene, they arise with greatest frequency at a handful of “hotspots.” A team led by Andrew Giacomelli, Broad institute member William Hahn of the Cancer Program, and colleagues now reports that these hotspots are no more cancer-promoting than other locations; they simply reflect the nature of the related carcinogens. As part of their investigation, the team created a comprehensive library of TP53 mutations and their effects in cells. Check out the full story in Nature Genetics and a news release from Dana-Farber Cancer Institute.

Pinpointing causal variants for autoimmune diseases

Fine-mapping is a statistical approach used to prioritize causal variants and improve mechanistic understanding of specific diseases. A team led by MPG associate member Soumya Raychaudhuri and co-first authors Harm-Jan Westra and Marta Martinez-Bonet at BWH implemented this technique to report on the functional significance of potentially causal variants for autoimmune diseases. In a study published in Nature Genetics, the researchers fine-mapped 76 rheumatoid arthritis and type 1 diabetes loci based on data collected from tens of thousands of individuals with either of the two diseases and control groups. Read more in GenomeWeb.

To learn more about research conducted at the Broad, visit broadinstitute.org/publications, and keep an eye on broadinstitute.org/news.