When a protective gene buffers a bad gene, the heart can beat

However, people with the same troublesome genes are thriving

"This gene is clearly very harmful -- the mice didn't even have a heartbeat, let alone survive," said Cecilia Lo, Ph.

The team found that a protective gene works against the bad gene, which explains why some people with this harmful gene not only survive, but only those with atrial septal defects (a hole in the heart) down

Congenital heart disease is one of the most common birth defects, affecting about 1% of live births

Working with Brian Feingold, MD, medical director of the Pediatric Heart Failure and Heart Transplant Program at UPMC Children's Hospital in Pittsburgh, Lo's team obtained genetic samples from eight members of a family who all had large atrial septal defects

To learn more about this genetic mutation, Lo's team used CRISPR-Cas9 gene editing technology to introduce the mutation in mouse embryos

The deaths in mice and the extreme rarity in humans suggest the mutation should be lethal, but since scientists obtained genetic samples from eight carriers of the relevant mutation whose hearts were beating, Xu created a model to observe in a petri dish what happens to patient cells

So Lo's team knew there was more to this story

"With the modern tools we have to explore genetics, we are realizing that not everything is what it seems

After studying the same three chromosomal parts inherited by all eight family members, Lo's team found nine additional genetic variants that were close to the bad TPM1 mutation

Heart beating was observed when the team introduced both deleterious and protective mutations in mouse embryos

The finding could have direct implications for helping families understand the risk of passing on genetic mutations to offspring, and could help guide clinical treatment, such as prompting doctors to consider earlier treatment or more frequently evaluate for dilated hearts and rhythm disturbances

Advances in science can also reveal macroscopic meanings, Professor Lo said

Other co-lead authors of the study are Dr.
Wenjuan Zhu et al.
from the Chinese University of Hong Kong
.