Brain disorders are among the leading causes of death and disability worldwide, affecting about 3.6 million Canadians. While we know that genetics play an important role, the specific genetic causes remain unknown for most people with the disorders. Advances in genome sequencing now allow us to read almost every part of our DNA, but most studies so far have focused only on the protein-coding regions, which make up just about 1.5% of our genome. The remaining 98.5% of the genome is often overlooked, even though much of it is made up of repetitive DNA sequences, sometimes referred to as the “genomic dark matter.”

One major type of repetitive DNA is called tandem repeats, which account for about 6% of the human genome. These are stretches of DNA where short sequences of nucleotides are repeated one after another. When these repeats become unusually long (known as a tandem repeat expansion), they can disrupt how genes work and lead to disease. To date, researchers have identified disease-causing mechanisms for only about 60 of the more than one million known tandem repeats.

My lab has developed a new method to detect and analyze tandem repeat expansions from genome sequencing data. In this project, we will apply our analytic strategies to large genome datasets to uncover how individual tandem repeat expansions contribute to brain disorders. Our findings will help fill major gaps in our understanding of the genetic causes of these conditions and may ultimately shorten the long diagnostic journey faced by many individuals and families who are affected by brain disorders.