Exomsekvenisering

Exomsekvenisering, also known as exome sequencing, is a genomic technique that focuses on sequencing the protein‑coding regions of the genome, called exons. These exons comprise about 1–2 % of the human genome but contain approximately 85 % of known disease‑causing mutations, making exomsekvenisering a cost‑effective approach for identifying genetic variants involved in Mendelian disorders, cancer, and other complex diseases.

The method was first popularised in the early 2000s when high‑throughput sequencing platforms became affordable. Exons are enriched from genomic DNA using hybrid capture or amplicon‑based strategies, then sequenced on next‑generation sequencers. Bioinformatic pipelines align reads to a reference genome, call variants, and filter for functional impact. The typical coverage for reliable variant detection is 50–100×, though higher coverage improves sensitivity for mosaicism and low‑frequency variants.

Clinical adoption began around 2011 with the diagnostic exome sequencing (DES) initiatives in Canada and Europe. Since then, exomsekvenisering has accelerated the discovery of novel disease genes and is now a standard diagnostic tool in many genetic clinics. In oncology, tumor exome sequencing can reveal actionable mutations guiding targeted therapies and immunotherapy decisions.

Benefits of exomsekvenisering include reduced sequencing costs compared to whole‑genome sequencing, simplified data interpretation, and the ability to detect both single‑nucleotide variants and small insertions/deletions. Limitations arise from incomplete coverage of all exons, difficulty in calling copy‑number variants, and challenges in interpreting variants of unknown significance. Additionally, non‑coding regulatory variants are missed, potentially limiting diagnostic yield.

Future directions involve integrating exomsekvenisering with transcriptomics and epigenomics to achieve a more comprehensive view of disease mechanisms, and refining variant‑annotation pipelines to enhance clinical relevance.