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Detection of tandem repeat expansion in neurological disorders

Principal Investigator:
  • Ryan Yuen, The Hospital for Sick Children
  • The Azrieli Foundation

Project Overview

In the past decade, rapid development of software has allowed detection of a wide variety of genetic risk factors in brain disorders. It has improved clinical diagnosis and gene discovery for numerous human brain disorders. However, the casual genetic risk factors identified so far generally confer less risk than expected from estimation for many disorders. For example, genetic risk factors have so far been identified in only fewer than 20% of the cases in autism spectrum disorder (ASD) despite its estimated up to 90% cases attributed to genetics. Such missing cases can be due to the technical hurdle of the the current sequencing technology in repetitive regions of the genome. In particular, gene-specific short tandem repeats (STRs), have been linked to over 40 known genetic disorders. Most of these are caused by increased length of the STRs (repeat expansions). Notably, each of these would have escaped detection by currently available tools. We have developed a comprehensive repeat expansion calling strategy that allow an unbiased genome-wide detection and genotyping of repeat expansions from WGS data. In this project, we will apply such optimized repeat expansion calling strategy to enable detection of known and novel functional and potentially pathogenic repeat expansions in ASD.