Next-Generation Sequencing

Identification of genetic causes of diseases is a bona fide requirement to establish diagnostic testing. The latter is of growing importance as in many Mendelian (monogenic) diseases, early diagnosis prevents a long diagnostic journey, results in a differentiated evaluation of the risk of recurrence for parents and other relatives, and enables the creation of a personalized screening program for in an increasing number of cases. Moreover, accurate genetic diagnosis is the foundation for a hopefully increasing number of clinical trials and treatment approaches.

Understanding genetic variation is key to gain insight into biological and potential disease-associated mechanisms. To this end, state-of-the-art high throughput sequencing technology is essential to determine an individual’s DNA sequence. Initially, the Institute of Human Genetics used the Sanger chain-terminating dideoxynucleotide method to sequence single genes. In 2009, the Institute established the RetChip, a first multigene panel chip to sequence retinal disease genes, followed in 2012 by a first Ion Torrent next-generation sequencing system. The latter systems allowed the sequencing of many genes in parallel and with reduced costs in time and personell. The capacity was then extended by acquisition of a sequencing platform with MiSeq and NextSeq 550 apparatuses. This enabled us to perform RNA sequencing (RNA-Seq) and whole-exome sequencing (WES) analyses.

Furthermore, since 2024 the capacity was further expanded by acquisition of NovaSeq X Plus, which enables us to perform fast, high quality, and robust sequencing by synthesis (SBS), including whole-genome sequencing (WGS) analyses.

With increasing sequence data accumulation and further demands on functional assessment of genetic variants, high throughput computational capacity becomes essential. We have many decades of experience with complex data and bioinformatic processing and evaluation of sequencing data.