“Implementation of next generation sequencing in molecular diagnostics – strategic considerations”
Hereditary disorders can be explained by one or more mutations in any of the ~ 20,000 genes. In order to detect these mutations diagnostic laboratories strive to have a DNA sequencing test for each gene known to be involved in a disorder. For genetic conditions explained by a single gene defect genetic testing is relatively simple. However, there are numerous conditions for which many genes are known. Apart from making the appropriate clinical diagnosis, a physician / clinical geneticist faces the problem which of the genes need to be tested in the laboratory. Moreover, for many (heterogeneous) diseases the genes are still unknown.
A new technology called Next Generation Sequencing (NGS) has made it possible to sequence multiple loci in parallel in a single test, i.e. the genome or the exome of individuals (all exons with intron / exon transitions from the ~ 20,000 genes). The search for a causative mutation in genetic heterogeneous disorders is therefore likely to be more effective using NGS. Initially, this diagnostic method is used for a number of common heterogeneous disorders: unexplained intellectual disability, congenital deafness, hereditary blindness, hereditary movement disorders, inherited disorders of the energy metabolism, and hereditary bowl cancer. Important aspects of the implementation of NGS as a diagnostic tool will be addressed; the informed consent procedure, description into our quality system, the laboratory and data-analysis workflow, as well as reporting to referring clinicians. This will be followed by a discussion on results of our diagnostic exome sequencing analyses.
H. Scheffer, PhD
associate professor clinical molecular genetics
head division Genome Diagnostics
Human Genetics, division Genome Diagnostics
Radboud University Nijmegen Medical Centre
www.dnadiagnostieknijmegen.nl
