What is the Dyrk1a Gene and How Does it Affect Autism? - Chromatography Explores

It has been known for over fifty years that there is a genetic component to autism when researchers found that identical twins often shared the condition. Scientists have since been working to find genetic markers or changes that could underlie autism. A process that has increased with the advent of recent DNA-based technologies.

A recent paper published in the journal Biological Psychiatry - Dyrk1a Mutations Cause Undergrowth of Cortical Pyramidal Neurons via Dysregulated Growth Factor Signaling – reports on new mechanisms that underlie brain growth that can be linked to a mutation in the Dyrk1a gene. The research team used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyse levels of proteins linked to autism.

Twins suggest genetics play a role

Since 1977, and the first autism twin study, research has shown that when autism rates in twins are compared, there is a likelihood that autism is heritable. If one twin has autism, there is an 80% chance that the other twin has it too. For fraternal twins, who develop from separate eggs and are genetically distinct, the corresponding rate of autism is 40%. There are also environmental factors that can contribute to autism too. But the relative contributions between genes and environment are a source of disagreement between researchers.

Dyrk1a is a gene found on chromosome 21 and encodes for an enzyme called dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A. It is thought to play a role in a pathway that regulates cell growth and is also associated with brain development. The gene is localized in the Down syndrome critical region of chromosome 21 and could be the gene associated with the learning development defects associated with Down syndrome.

Chromatography identifies the proteins

Researchers from Scripps Research, Florida have found a mechanism underlying brain undergrowth in mice with Dyrk1a gene. They identified 56 cellular proteins that were deficient and 33 that were increased in the mice using LC-MS/MS. Increasing the speed of chromatographic analysis is discussed in the article, Faster Time to Results for Ultra-Performance Liquid Chromatographic Separations of Metal-Sensitive Analytes.

As many as 200 genes have been associated with autism spectrum disorders, but little is known about their roles and relationships. Fewer than 1% of people diagnosed with autism spectrum disorder have the Dyrk1a mutation. In conclusion the team state

...these findings identify a previously unknown mechanism through which Dyrk1a mutations disrupt growth factor signaling in the developing brain, thus influencing neuronal growth and connectivity. Our results place DYRK1A as a critical regulator of a biological pathway known to be dysregulated in humans with autism spectrum disorder and intellectual disability.