Why does Down syndrome cause heart defects?
Researchers have used mouse models to ask which genes cause the heart defects often seen in Down syndrome.
Down syndrome is a condition caused by having an extra copy of one of the 46 chromosomes found inside human cells. Specifically, instead of two copies, people with Down syndrome are born with three copies of chromosome 21. This results in many different effects, including learning and memory problems, heart defects and Alzheimer’s disease. Each of these different effects is caused by having a third copy of one or more of the approximately 230 genes found on chromosome 21. However, it is not known which of these genes cause any of these effects, and how an extra copy of the genes results in such changes.
Now, Eva Lana-Elola and co-workers have investigated which genes on chromosome 21 cause the heart defects seen in Down syndrome, and how those heart defects come about. This involved engineering a new strain of mouse that has an extra copy of 148 mouse genes that are very similar to 148 genes found on chromosome 21 in humans. Like people with Down syndrome, this mouse strain developed heart defects when it was an embryo.
Using a series of six further mouse strains, Lana-Elola and co-workers then narrowed down the potential genes that, when in three copies, are needed to cause the heart defects, to a list of just 39 genes. Further experiments then showed that at least two genes within these 39 genes were required in three copies to cause the heart defects.
The next step will be to identify the specific genes that actually cause the heart defects, and then work out how a third copy of these genes causes the developmental problems.
To find out more
Read the eLife research paper on which this eLife digest is based: “Genetic dissection of Down syndrome-associated congenital heart defects using a new mouse mapping panel” (January 14, 2016)
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