Whole-genome detection and interpretation of repeat expansions in autism and related disorders

Advancements in genome analysis have greatly improved gene discovery and clinical diagnosis for many human diseases, with genome sequencing becoming the current standard. While genome-sequencing data has enabled the identification of all classes of genetic variation, there are still difficulties in resolving genetic changes in more complex disorders, such as autism spectrum disorder (ASD). Despite over 100 genetic factors identified as being associated with ASD, the underlying genetic cause of 80% of all ASD is still unknown. 6% of the human genome is comprised of tandem repetitive DNA, and certain repeats have been associated with ~40% of ASD cases. Dr. Ryan Yuen, a Scientist in Genetics & Genome Biology (GGB) at SickKids, and Dr. Stephen Scherer, a Senior Scientist in GGB and Director of The Centre for Applied Genomics at SickKids, have led their teams in determining the impact of tandem repeats on the genetic risk of developing ASD. They have developed a method to detect tandem repeats allowing identification of gene candidates involved in ASD, which can be applied to other complex genetic disorders. From an analysis of clinical data of more than 17,000 samples and controls, this method provides a more sensitive approach in capturing ASD diagnoses that would be otherwise missed using current standards.