Identification and Prioritization of Causal Variants of Human Genetic Disorders from Exome or Whole Genome Sequencing Data

Abstract

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. With genome sequencing entering the clinics as diagnostic tool to study genetic disorders, there is an increasing need for bioinformatics solutions that enable precise causal variant identification in a timely manner. Background Workflows for the identification of candidate disease-causing variants perform usually the following tasks: i) identification of variants; ii) filtering of variants to remove polymorphisms and technical artifacts; and iii) prioritization of the remaining variants to provide a small set of candidates for further analysis. Methods Here, we present a pipeline designed to identify variants and prioritize the variants and genes from trio sequencing or pedigree-based sequencing data into different tiers. Results We show how this pipeline was applied in a study of patients with neurodevelopmental disorders of unknown cause, where it helped to identify the causal variants in more than 35% of the cases. Conclusions Classification and prioritization of variants into different tiers helps to select a small set of variants for downstream analysis.