Some 134 genes have been implicated in causing congenital heart disease (CHD), a birth defect
that affects eight in 1,000 newborns, according to the National Institutes
Specific genetic errors that trigger congenital heart disease (CHD) in humans can be reproduced reliably in Drosophila melanogaster
- the common fruit fly - an initial step toward personalized therapies for patients in the future.
‘Studying congenital heart disease (CHD) in fruit flies provides a fast and simple first step in understanding the roles that individual genes play in disease progression.’
"Studying CHD in fruit flies provides a fast and simple first step
in understanding the roles that individual genes play in disease
progression," says Zhe Han, a principal investigator and
associate professor in the Center for Cancer & Immunology Research
at Children's National Health System and senior author of the paper
published in eLife
"Our research team is the
first to describe a high-throughput in vivo validation system to screen
candidate disease genes identified from patients. This approach has the
potential to facilitate development of precision medicine approaches for
CHD and other diseases associated with genetic factors," Han says.
The research team led by Han used high-throughput techniques
to alter the activity of dozens of genes in flies' hearts simultaneously
in order to validate genes that cause heart disease.
"Our team was able to characterize the effect of these specific
genetic alterations on heart development, structure and activity," Han
adds. "The development of the human heart is a complicated process in
which a number of different cell types need to mature and differentiate
to create all of the structures in this essential organ. The precise
timing of those cellular activities is critical to normal heart
development, with disruptions in the structure of proteins called
histones linked to later heart problems.".
Of 134 genes studied by the research team, 70 caused heart defects
in fruit flies, and several of the altered genes are involved in
modifying the structure of histones. Quantitative analyses of multiple
cardiac phenotypes demonstrated essential structural, functional and
developmental roles for these genes, including a subgroup encoding
histone H3K4 modifying proteins. The scientists then corroborated their
work by reliably reproducing in flies the effect of specific genetic
errors identified in humans with CHD.
"This may allow researchers to replicate individual cases of CHD,
study them closely in the laboratory and fashion treatments personalized
to that patient specifically," he adds. "Precise gene-editing
techniques could be used to tailor-make flies that express a patient's
specific genetic mutation. Treating CHD at the level of DNA offers the
potential of interrupting the current cycle of passing along genetic
mutations to each successive generation."