Flies help decipher genetics behind heart defects
Studying congenital heart disease in fruit flies provides a fast way to start to understand which genes are involved.
Around one in 100 children are born with heart defects caused by congenital heart disease. Studying the genetic sequences of people with congenital heart disease has revealed many genes that may play a role in causing the condition, but few of these findings have been confirmed experimentally in animal model systems.
The fruit fly species Drosophila melanogaster is often used in genetic studies because it is a relatively simple organism. The insights gained from studying flies are often valuable for determining the direction of subsequent investigations in more complex animals — such as humans — that involve experiments that are more costly and less efficient.
Jun-Yi Zhu, Yulong Fu and colleagues have now used fruit flies to investigate the effects of 134 genes that have been suggested to contribute to congenital heart disease. The investigation used a method that rapidly allowed the activity of specific genes to be altered in the flies. The effects that these alterations had on many aspects of heart development, structure and activity were then measured. Of all the genes tested, 70 caused heart defects in the flies. Several of these genes help to modify the structure of proteins called histones; these modifications play important roles in heart cell formation and growth.
Further tests showed that the effects of specific genetic errors that had been identified in people with congenital heart disease could be reliably reproduced in the flies. This may allow individual cases of congenital heart disease to be replicated and studied closely in the lab, helping to create treatments that are personalised to each patient.
Studying congenital heart disease in flies provides a fast and simple first step in understanding the roles that different genes play in the disease. Moving forward, precise gene editing techniques could be used to generate flies to examine the role of each of the genetic mutations that occur in individual patients. Ultimately, when gene editing techniques are ready to be used in humans, this could lead to cures for congenital heart disease at the DNA level, so that these mutations won’t be passed on to the next generation.
To find out more
Read the eLife research paper on which this eLife digest is based: “High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila”(January 20, 2017).