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.