We performed whole exome sequencing in 16 AGRE patients, selected because they showed the largest total proportion of their genome homozygous (∼1%–9%) of all patients in the collection. We reasoned that some of the runs of homozygosity would contain homozygous causative mutations. Whole exome sequencing allows for the high-throughput, unbiased survey of all exonic variation in a patient, including any known mutations. Sequencing was performed using the Illumina Genome Analyzer II platform following enrichment of exonic sequences using Agilent's SureSelect Human Exome Kit. We obtained an average coverage of 92% at 20X (Table S1), and identified an average of 34,615 total variants per exome (Table S2), subsequently filtering them to identify rare, likely deleterious changes. Since we wanted to identify rare private mutations, common variants identified by the 1000 Genomes project and dbSNP130 were filtered out, and remaining variants were subject to an in-house bioinformatics pipeline to annotate variants that may disrupt gene function (by altering the coding sequence, the splice sites, or truncating the protein). On average, 735 variants per exome were potentially pathogenic, and out of these, 39
