An Integrated Genomic and Epigenomic Approach to Dissect the Aetiology of Motor Neuron Disease (2015–2017)
Abstract:
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND), but the two terms are often used interchangeably. It is a progressive and terminal neurological disease that destroys motor neurons, which control muscle activity, such as
walking and breathing. It mostly affects people >40 years old and most patients die within 3 years. In Australia, 2 people are diagnosed and die from ALS each day, with a total of 1,900 people living with ALS. There is no specific test for its diagnosis and there are no cures; the approved treatment (benzothiazole riluzole) only prolongs survival by 3 months. Ninety percent of cases have no known affected relatives, but its heritability of ~50% suggests that genetics play a significant role. Epigenetic marks, such as methylation have also been suggested to affect ALS, but research is still in infancy. Currently, specific biomarkers or environmental risk factors for ALS remain unknown. Therefore, elucidating the genetic causes of ALS is important for ALS research to advance. Our centre, the newly established Centre for Neuroscience and Statistical Genomics at QBI, UQ, and our collaborators have invested time and
funds to build up a rich in house dataset of 1,300 ALS cases and 3,100 controls, and designated ALS as a research focus. The clinical data on these subjects are enriched with 7M single nucleotide polymorphism (SNP) data, 600K variants from exome sequencing and 450K methylation probes. Within the next four years we hope to expand this resource significantly. I aim to apply my statistical genetic, computational and bioinformatics expertise to these resources to build an independent group that focuses on dissecting the genetic and epigenetic aetiologies of ALS to discover novel genes and epigenetic marks, and to dissect their biological function. This new knowledge is crucial for finding effective diagnosis, treatment and cure for ALS.
