Case 1
DNA was extracted from proband’s whole blood and prepared using TruSeq DNA PCR-free libraries (Illumina). The Illumina HiSeq X Ten System (Illumina) was used to sequence the proband’s DNA to a median 84x whole-genome coverage. Sequence reads were aligned to the GRCh37 reference genome (including decoy sequences from the GATK resource bundle) using the BWA-MEM (Li, 2013). The resulting BAM files were de-duplicated, INDEL realignment and base quality recalibration was performed using Picard tools (Toolkit, 2019) followed by the GATK variant discovery toolkit using a best practices workflow (DePristo et al., 2011). Quality control metrics indicated high quality sequence, alignment and variant calling. Sequence variant data for the proband in VCF file format was loaded into the Fabric Genomics (formerly Omicia) platform (https://fabricgenomics.com/), and genes involved in the urea cycle were examined in detail within this framework to identify variants that may have an impact on gene function.