Using NGS to diagnose patients with rare genetic diseases

OBJECTIVE: The aim of this thesis is to summarize the contributions of NGS techniques in the genetic diagnostics, and discuss some challenges with the NGS-techniques. BACKGROUND: Next generation Sequencing (NGS) provides important genetic tools such as Whole Genome Sequencing (WGS), Whole Exome Sequencing (WES) and Targeted Sequencing of gene panels. The techniques are used in the genetics to identify disease-causing mutations in known genes and to further analyse patients without a genetic diagnosis - thus identifying “novel diseases genes”. The NGS techniques have over the last decade become important approaches in medical genetics. METHOD: Mainly a systematic search on the databases; PubMed and Cochrane library with a main focus on systematic reviews, but also some single studies used as examples. The articles are retrieved in the period between January 2017 and January 2018. Only articles written in English are included DISCUSSION AND CONCLUSION: NGS-techniques are the best methods detecting single nucleotide variation (SNVs) and small deletions and duplications (INDELs), but not efficiently detecting larger structural variants and repeat expansions. Long-read sequencing will be better at detecting these variants and is expected to play an important role in the future use of NGS. In addition, the main bottleneck in the genetics today when using NGS to identify disease-causing mutations is to understand the clinical significance of the genetic variants detected. This might change in the future as NGS are fast developing tools that are used to reveal knowledge of gene function and the consequences of mutations in patients