The researchers found that the presence of a third copy of the Dyrk1a gene and at least three other genes are responsible for structural changes in the face and skull of Down syndrome.
Down syndrome affects 1 in 800 live births and is known as a “genetic dose disorder”, which involves changes in the copy number of a gene.
People with Down syndrome are known to have three copies of chromosome 21 instead of just two. However, it is not entirely clear which genes copied within this chromosome are responsible for the different aspects of the syndrome.
Using genetic engineering, teams led by Victor Tipulovic of the Francis Crick Institute and Elizabeth Fisher of King’s College London created mouse strains with copies of three regions on mouse chromosome 16 that mimic the presence of a third chromosome 21 .
The mice show many of the features associated with Down syndrome, including changes in the shape of the face and skull.
Previous research has linked a gene called Dyrk1a to Down syndrome, so researchers wanted to test how it affected craniofacial abnormalities.
The team showed that mice with an extra copy of Dyrk1a had fewer cells in the frontal bones of the skull and face. Also, at the base of the skull, cartilaginous joints called synchondrosis are abnormally fused together.
These effects were partially reversed when the third copy of Dyrk1a was removed, suggesting that three copies of Dyrk1a are required to cause these changes in the skull.
The researchers believe that having a third copy of Dyrk1a inhibits the growth of neural crest cells, which are important for bone formation in the front of the skull.
Research has shown that, in addition to Dyrk1a, three other genes also contribute to changes in the skull, but more research is needed to confirm their identities.
Victor Tipulevich, group chair of the Down Syndrome Center at Creek, said: “There are currently limited treatments available for aspects of Down syndrome that have adverse effects on its plaques, such as congenital heart disease and cognitive impairment, so it is very important that we identify the genes that are important. Understanding the genes involved in head and face development gives us “evidence for other aspects of Down syndrome, such as heart disease. And because Dyrk1a is key to craniofacial abnormalities, there are changes in other Down syndromes as well.”
Researchers at King’s College London used morphometry tools to map the changing shape of the skulls of mice and showed that these changes in skull shape were very similar to those observed in people with Down syndrome.
This research is part of an ongoing project to understand the genetics of Down syndrome. Researchers aim to identify genes associated with heart defects and cognitive impairment, bringing them one step closer to understanding how to develop targeted treatments for these aspects affecting the health of Down syndrome.
Source: Medical Express
Source: Arabic RT
