The discovery of a 'switch' that modifies a gene known to be essential for normal heart development could explain variations in the severity of birth defects in children with DiGeorge syndrome.
Researchers from the Walter and Eliza Hall Institute made the discovery while investigating foetal development in an animal model of DiGeorge syndrome. DiGeorge syndrome affects approximately one in 4000 babies.
Dr Anne Voss and Dr Tim Thomas led the study, with colleagues from the institute's Development and Cancer division, published today in the journal Developmental Cell.
Dr Voss said babies with DiGeorge syndrome have a characteristic DNA mutation on chromosome 22 (22q11 - chromosome 22, long arm, band 11), but exhibit a range of mild to severe birth defects, including heart and aorta defects. "The variation in symptoms is so prominent that even identical twins, with the exact same DNA sequence, can have remarkably different conditions," she said. "We hypothesised that environmental factors were probably responsible for the variation, via changes to the way in which genetic material is packaged in the chromatin," Dr Voss said.
Chromatin is the genetic material that comprises DNA and associated proteins packaged together in the cell nucleus. Chemical marks that sit on the chromatin modify it to instruct when and where to switch genes on or off, making a profound difference to normal development and cellular processes.
The research team found a protein called MOZ, the 'switch' which is involved in chromatin modification, was a key to explaining the range of defects seen in an animal model of DiGeorge syndrome. "MOZ is what we call an chromatin modifier, which means it is responsible for making marks on the chromatin that tell genes to switch on or off," Dr Voss said.