Library construction and multiplex whole exome capture
Genomic DNA libraries from which exomes are captured were constructed according to British Columbia Cancer Agency Genome Sciences Centre plate-based and paired-end library protocols on a Biomek FX liquid handling robot (Beckman-Coulter, USA). Briefly,  1ug of high molecular weight genomic DNA was sonicated (Covaris) in 60uL volume to 200-300bp. Sonicated DNA was purified with magnetic beads (Agencourt, Ampure). The DNA fragments were end-repaired, phosphorylated and bead purified in preparation for A-tailing.  Illumina sequencing adapters were ligated overnight at 16oC and adapter ligated products bead purified and enriched with 6 cycles of PCR using primers containing a hexamer index that enables library pooling. 175ng for each of 6 different libraries were pooled prior to whole exome capture using Agilent SureSelect V5+UTR probes. The pooled libraries were hybridized to the RNA probes at 65oC for 24 hours. Following hybridization, streptavidin-coated magnetic beads (Dynal, MyOne) were used for exome capture. Post-capture material was purified on MinElute columns (Qiagen) followed by post-capture enrichment with 8 cycles of PCR using primers that maintain the library-specific indices. Paired-end 75 base reads were sequenced in 2 lanes of an Illumina HiSeq2000 instrument per pool.