Bioinformatics of germline variant discovery for rare disease diagnostics: current approaches and remaining challenges.

ABSTRACT: Next-generation sequencing (NGS) has revolutionized the field of rare disease diagnostics. Whole exome and whole genome sequencing are now routinely used for diagnostic purposes; however, the overall diagnosis rate remains lower than expected. In this work, we review current approaches used for calling and interpretation of germline genetic variants in the human genome, and discuss the most important challenges that persist in the bioinformatic analysis of NGS data in medical genetics. We describe and attempt to quantitatively assess the remaining problems, such as the quality of the reference genome sequence, reproducible coverage biases, or variant calling accuracy in complex regions of the genome. We also discuss the prospects of switching to the complete human genome assembly or the hu

SUBMITTER: Barbitoff YA 

PROVIDER: S-EPMC10810331 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature