New mutations that are absent in parents but appear in their offspring account for at least 10 percent of severe congenital heart disease, reveals a massive genomics study led by researchers at the Yale School of Medicine.
According to a press release put out by Yale, an analysis of all the genes of more than 1800 individuals found hundreds of mutations in that can cause congenital heart disease, the most common form of birth defect that afflicts nearly 1 percent of all newborns. In particular, the study found frequent mutations in genes that modify histones, proteins that package DNA in the nucleus and orchestrate the timing and activation of genes crucial to development of the fetus. The results of the study, part of the Pediatric Cardiac Genomics Consortium funded by the National Heart Lung and Blood Institute, were published online May 12 in the journal Nature.
The mutations can occur at the same site, and both increase and decrease the modification histone proteins, said Martina Brueckner, professor of pediatrics and genetics at Yale and another senior author of the study. The results suggest a very sensitive developmental system that might also be influenced by environmental factors in development.
Samir Zaidi and Murim Choi of Yale were co-lead authors of the paper. Researchers from Harvard University, Columbia University Medical Center, the Perelman School of Medicine at University of Pennsylvania, and Icahn School of Medicine at Mt. Sinai shared senior authorship.