Library preparation and whole-exome sequencing (WES)
DNA samples were extracted by phenol-chloroform followed by ethanol precipitation [27]. Genomic libraries were constructed with 1 µg of genomic DNA using the following kits: Sureselect QXT V6 (Agilent Technologies), OneSeq Constitutional Research Panel (Agilent Technologies), or xGen Exome Research Panel v1.0 (IDT - Integrated DNA Technologies). The sequencing of enriched libraries was performed on the Illumina HiSeq 2500 platform using 150 base paired-end reads. The sequences were aligned to the GRCh37/hg19 human genome reference with the BWA_MEM algorithm [28]. Picard tools (v.1.8, http://broadinstitute.github.io/picard/) were used to convert the SAM file into BAM and to mark PCR duplicates. The Genome Analysis Toolkit (GATK 3.7) [29] was used to realign indels, recalibrate the bases, and call (Unified Genotyper) and recalibrate variants (VQSR). Finally, multiallelic variants were split into different lines using the script split_multiallelic_rows.rb from Atlas2 [30] to obtain the VCF files used for analysis.