Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Huntington disease (HD) is a devastating genetic disorder of the brain marked by involuntary movements, cognitive decline, and psychiatric disturbances. Symptoms of HD are progressive, leading to death 15-20 years after diagnosis. HD is caused by a mutation in the Huntingtin gene, which leads to toxic effects in neurons. HD patients typically carry one mutated copy of the Huntingtin gene and one normal copy. A promising strategy for the treatment of HD is to turn off, or silence, the copy of the gene which carries the mutation while sparing the normal copy. Turning off the mutant gene can be accomplished by the use specialized molecules targeting DNA sequences that differ between the normal and mutated gene. The HD mutation itself cannot be directly targeted for silencing, but nearby genetic variants are known to be linked to the mutation and offer alternative targets. The extent of these variants linked to the HD mutation, which offer new targets for selective silencing of the HD gene, is not well understood. This study will fully determine genetic variants associated with the HD mutation in different populations, and define optimal targets for therapeutic silencing of the mutant gene. In summary, this work will identify specific genetic targets for therapeutic silencing of the HD gene, offering treatment for the greatest number of HD patients worldwide.