2.2 | Exome Sequencing
DES was performed as previously described (Farwell, 2015; Farwell Hagman, 2017). In brief, samples were prepared using either the SureSelect Target Enrichment System (Agilent Technologies, Santa Clara, CA), SeqCap EZ VCRome 2.0 (Roche NimbleGen, Madison, WI), or the IDT xGen Exome Research Panel V1.0 (Integrated DNA Technologies, Coralville, IA). Sequencing was performed using paired-end, 100 or 150-cycle chemistry on the Illumina HiSeq, NovaSeq, or NextSeq (Illumina, San Diego, CA). Bioinformatics filtering removed common benign variants, intergenic and 3’/5’ UTR variants, intronic variants outside ±6, and non-splice-related synonymous variants. Family history-based filtering and inheritance models were applied to the data.