This course covers state-of-the-art and best-practice tools for the analysis of genomes. We describe, and give hands-on experience of, the entire analysis workflow from raw data generated by a sequencing machine to deriving variant calls (e.g. Single Nucleotide Variants) that are ready for downstream analysis, interpretation and prioritisation. We will describe the steps involved to go from sequencing library to a prioritised, clinically-relevant list of DNA variants. Practical sessions will use the user-friendly Galaxy interface (https://usegalaxy.org/) to demonstrate tasks such as alignment, quality control, variant-calling and annotation.