Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

The Guitar Ensemble February 8, 2003

Concert Program for The Guitar Ensemble February 8, 2003

2004-05 Board of Trustees

The 2004-2005 Board of Trustees. Pictured here from left to right are: Front Row - Val Fleming; Dr. Patricia Teal; Wendy Staff; Dr. Norris Walker, Chair; Dr. David Atkinson, President and Vice Chancellor; Dr. Val Jaeger; Donna Scott; and Steven Lalinovich. Middle Row - Mike Farrell, Secretary to the University; Rudi Kroeker; Brandon Larry, President, Brock University Students' Union; Dr. Terry Boak, Vice-President, Academic and Provost; Mitzi Banders; Geeta Powell; Dr. Sid Segalowitz; Tom Gauld; Karin Jahnke-Haslam; and Dr. Mohammed Dore. Back Row - David Edwards, Immediate Past Chair; Bruce Wormald; Willy Heldbuechel, Vice-Chair; Brad Clarke; David Howes, Vice-Chair; Mark Steinman; Peter Partridge; Michael Sidenberg; Angelo Nitsopoulos; Steven Pillar, Vice President, Finance and Administration; Ron Dubien, Chief Information Officer. Absent from photo - Dr. Raymond Moriyama, Chancellor; Eleanor Ross; Jagoda Pike; Dr. Mary Frances Richardson; and Nick Brown.