Third Dyrk1a Gene in Individuals With Down Syndrome Is Associated With Changes in Skull
A new study revealed that a third copy of gene Dyrk1a in individuals with Down Syndrome is linked to the changes in their skulls. Additionally, three other genes were also responsible for the changes taking place.
Gene Dyrk1a in Individuals With Down Syndrome
Researchers from the Francis Crick Institute, King's College London, and University College London examined the genetics underlying modifications to the structure and shape of the face and skull in a mouse model of Down syndrome, EurekAlert! reported.
The changes in Development known as craniofacial dysmorphology, including shortened back-to-front length and widened diameter of the head, was found to be caused by having a third copy of the gene Dyrk1a and at least three other genes, according to a recently published study.
The Dyrk1a gene causes intellectual disability with microcephaly and epilepsy. When Dyrk1A and splicing factor 9G8 are coexpressed, their ability to control tau exon ten splicings are suppressed, and they move from the nucleus to the cytoplasm, according to NIH.
The condition affects 1 in 800 live births. Variations in the number of copies of a gene characterize Down Syndrome. Chromosome 21 is present in three copies in those with Down syndrome. Having three copies of specific genes on this chromosome causes the condition. However, it remains unknown which genes are responsible.
Through genetic engineering, groups led by Victor Tybulewicz of the Francis Crick Institute and Elizabeth Fisher of University College London produced mouse strains that mimicked the presence of a third chromosome 21 by duplicating three areas on the mouse chromosome 16. The mice exhibit various characteristics linked to Down syndrome, including facial and skull modifications.
The study aimed to examine how the Dyrk1a gene affected craniofacial dysmorphology in light of prior research connecting it to features of Down Syndrome.
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Extra Dyrk1a Gene And Changes in Skull
Jeremy Green's team at King's College London demonstrated that mice with an additional copy of Dyrk1a had fewer cells in the bones in their face and the front of their skull. Additionally, the synchondroses, which are cartilaginous joints at the base of the skull, were abnormally fused.
The removal of the third copy of Dyrk1a partially reversed these effects, demonstrating the necessity of three copies of Dyrk1a for these alterations to occur in the skull.
According to the researchers, the proliferation of neural crest cells, which are required to create the bones at the front of the skull, is thought to be hampered by harboring a third copy of Dyrk1a.
They must identify the key genes because few treatments are currently available for the poor health effects of Down syndrome, such as congenital heart defects and cognitive impairment, according to Victor Tybulewicz, Group Leader of the Down Syndrome Laboratory at the Crick, who worked with first author Yushi Redhead.
He added that they could gain insight into other features of Down syndrome, such as cardiac issues, by understanding the genetics involved in the head and face development. Given how important Dyrk1a is for craniofacial dysmorphology, it is very likely that it also contributes to other alterations in Down syndrome.
King's College London researchers utilized shape-measuring instruments to map the mice's altering skull shapes. These abnormalities in the form of the skull were strikingly comparable to those observed in individuals with Down syndrome.
Green added that they could use both relatively conventional and some quite new ways for comparing complex anatomical forms with the assistance of excellent collaborators from the University of Calgary in Canada and a medical imaging software department here at King's. These were wise enough to detect variations even in fetuses. It gave them hints about how those genes produce the differences they do, in addition to helping us pinpoint the sites of the genes that cause Down syndrome.
The study was published in Development.
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