Genome-wide repeat expansions in complex disorders: beyond the coding sequence

Identification of underlying genetic factors has provided important information on the functional pathways involved in many of complex disorders. However, the casual genetic factors identified in many complex disorders so far generally confer less risk than expected from the empirical estimates of their heritability. Tandem DNA repeats make up around 6% of the human genome and have been associated with more than 40 monogenic disorders, but their involvement in complex disorders is largely unknown. I will present our novel approach to detect genome-wide tandem repeat expansions. This approach has led to the identification of rare tandem repeat expansions contributing to autism spectrum disorder and other related conditions. It provides a model to search for missing heritability in other complex disorders.