Patients: group of Polish GTS patients and their families (n=185).
Problem/Task: the construction of an oligogenic risk model of GTS based on possibly pathogenic variants likely contributing to the risk of GTS and TDs.
Solution: Identification of rare variants using the Intelliseq Germline Workflow on whole-genome data. Within the workflow, fastq files were assessed for quality with FastQC. The files were then aligned to the Broad Institute Hg38 Human Reference Genome with GATK 4.0.3. Duplicate reads were removed with Picard and base quality Phred scores were recalibrated using the GATK covariance recalibration. Variants were called with the GATK HaplotypeCaller to give genomic variant calling files (gvcf). The gvcf files were then subjected to joint genotyping with GATK via GenomicsDB to generate a joint vcf file.
Result: The oligogenic risk model for Gilles de la Tourette syndrome based on whole-genome sequencing data. The model includes putatively deleterious rare and non-coding variants in and near GTS candidate genes that may cooperatively contribute to GTS etiology and provides a novel approach to the analysis of clinical WGS data.
The research was conducted by:
Laboratory of Neurogenetics, Mossakowski Medical Research Centre, Polish Academy of Sciences; Department of Neurology, Warsaw Medical University; Laboratory of Pharmacogenomics, Department of Molecular Neuropharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences.
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