Trinity researchers discover breakthrough with autism, epilepsy and schizophrenia

The research, led by Professor Aoife McLysaght, will be published in the Nature Communications journal


Researchers in Trinity’s department of genetics have isolated a short list of genes that could be responsible for a variety of neurodevelopmental disorders and diseases, including autism, epilepsy, schizophrenia and ADHD.

A team led by Professor Aoife McLysaght carried out the research and the findings will be published in the journal Nature Communications.

The human genome is composed of over 20,000 genes which are responsible for the production of proteins in the body. Professor McLysaght and PhD candidate Alan M. Rice studied regions of the genome called “copy number variants” (CNVs), which are copied or deleted in some people. Sometimes the genes within these regions function similarly regardless of duplication but variations in some CNVs are associated with many developmental disorders and diseases. A major challenge lies in finding which genes within these regions are responsible for the negative effects.

Professor McLysaght, head of the department of genetics and a Fellow of the College, said: “Our idea was that there must be some genes within these regions with ‘Goldilocks’ properties: too much or too little duplication, and things don’t work properly. The number of copies must be just right.”

The Trinity team looked back over evolutionary history to discover which genes don’t tolerate increases or decreases over time. This segment of their work suggested that the solution to this is in the presence of the Goldilocks genes within the disease-causing CNVs. Genes that are key in human development, those that kick into action at an early embryonic stage, seem to be particularly important.

The team also found that CNVs associated with developmental disorders tended to vary far less in terms of the number of gene copies present than was the case for CNVs whose variations are not associated with disorders. This pattern held true across different mammal species, from sheep to dogs, and from rabbits to gorillas.

The implication from this is that wider variations in the number of gene copies may evolve and persist in benign CNVs but not in disease-linked CNVs – the effects would be too physiologically serious to be passed on by an individual to his/her children.
Alan M. Ryan, speaking to Trinity News, noted the potential applications of the team’s research for the diagnosis and treatment of these disorders in the future.