Sequencing details are included in the online Supplementary material. We used the integrated GotCloud program for alignment and variant calling (Jun et al. 2015). After alignment, read clipping and duplicate removal, average sequencing depth genome-wide was 11×. Quality-control information is shown in online Supplementary Table S3. Variant calling was done with GotCloud defaults, using Beagle for linkage disequilibrium refinement of called genotypes (online Supplementary Table S4). To estimate power of 11× sequencing for rare variant discovery we compared the sequence variant calls to Illumina HumanExome array variant calls. The sequenced calls identified 11484 of the 15791 singletons on an Illumina HumanExome array genotyped on the same sample (73%), 10 308 of the 10 990 doubletons (94%) and 6488 of 6573 tripletons (99%). Of 151 860 monomorphic sites on the exome array, sequencing called 2951 of these sites polymorphic (about 2%). We next estimated genotype concordance between the sequence variant calls and the Illumina HumanExome and 660W-Quad genotypes. Autosomal genotypes showed 99.91% concordance (online Supplementary Fig. S1). In sum, the sequence data provided accurate genotype calls, even for rare variants including singletons and doubletons.
