Exome sequencing
Whole exome sequencing (WES) was performed at the Massachusetts Eye and Ear Ocular Genomics Institute using Agilent SureSelect Human All Exon v6 with the Illumina HiSeq 2000, or at the Broad Institute of MIT and Harvard using a TWIST Biosciences custom exome bait with the Illumina Novaseq 6000. We used the Ocular Genomics Institute bioinformatics pipeline (Consugar et al., 2015) for alignment and variant calling that includes the Burrows-Wheeler aligner (Li et al., 2010), GATK (https://gatk.broadinstitute.org/), GERP (http://mendel.stanford.edu/SidowLab/downloads/gerp/), Exome Aggregation Consortium (ExAC) (http://exac.broadinstitute.org ), SIFT (http://sift.jcvi.org/), and PolyPhen-2 (http://genetics.bwh.harvard.edu/pph2/). A coverage depth cutoff of 10x was applied. Heterozygous was defined as a fraction of a variant base between 0.25–0.75 and homozygous was defined as above 0.75. Average coverage was 105x for 99% of coding sequences.