Next Generation Sequencing:
new possibilities in genetic diagnostics.
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.
Marcel Nelen, PhD Clinical Molecular Geneticist
With this abstract Marcel Nelen will talk about the practical implementation of NGS; H. Scheffer ,with the same abstract, will deal more with strategic considerations.
