A Single Faulty Gene Copy Can Unravel the Heart’s DNA

Gladstone Institutes researchers found that cutting TBX5 levels in developing heart cells by half destabilizes chromatin loops and 3D DNA organization.

That disruption alters the activity of many heart-related genes and offers a mechanism for congenital heart disease caused by TBX5 haploinsufficiency.

The study shows that losing one functional copy of a gene can trigger disease by breaking genome architecture, not just by lowering gene dose.

It also suggests that faulty 3D genome folding may contribute to other haploinsufficiency disorders.