Discovery: New gene involved in heart disease

Friday, 12 July, 2013

Understanding the heart is one of science’s greatest challenges because of the remarkable complexity of this essential pump.

Heart defects are among the most common problems found in newborn babies and heart disease is a leading cause of death in adults. And one new approach is to search for mutations that affect heart formation.

Using this method, a group led by Professor Lee Adamson of the Samuel Lunenfeld Research Institute in Toronto, Canada, in collaboration with Professor Merlin Crossley’s UNSW research team, has identified a new gene involved in heart development – a DNA-binding protein termed Klf3.

The work is published in the journal PLOS Genetics.

The Canadian group carried out a random genetic screen in mice and identified a pedigree that had an inherited defect of the aorta, the major artery carrying oxygenated blood from the heart.

Using a combination of breeding and modern genomic techniques they narrowed in on the relevant gene and unexpectedly identified Klf3.

Klf3 is a DNA-binding protein with multiple roles in development but which had not previously been implicated in heart disease.

“This was a remarkable finding,” says Professor Crossley. “One day Lee called me out of the blue and told me she had found a mutation in Klf3. We’d been working on Klf3 for many years and were able to propose that the mutation would affect genes which Klf3 regulated."

The groups collaborated for nearly five years determining how the mutation altered the ability of Klf3 to find its target genes and how this resulted in heart disease.

The results represent another step in new genomic approaches to establishing the molecular pathways involved in mammalian development and in understanding processes that may one day be modified to restore heart function.

Media contacts:

Professor Merlin Crossley: 9385 7916,

UNSW Science media: Deborah Smith: 9385 7307, 0478 492 060,