In the past 20 years, the accuracy, speed, efficiency, and cost-effectiveness of DNA sequencing has improved dramatically. Now, new innovative sequencing technologies arise which enable the sequencing of hundreds of genes in a single individual with a suspected genetically heterogeneous disorder, or complex disease predisposition. These new techniques speed up, and also reduce the costs of DNA sequencing drastically. However, before these techniques can be used on a large scale in medical practice, several challenges must still be overcome and validation of the diagnostic applications is required.

In this project the implementation of a high throughput sequencing technique called massively parallel sequencing (MPS) in genetic disease diagnostics is envisaged. This MPS system can read 25 million bases of genetic code within four hours. This is about 100 times faster than the current state-of-the-art Sanger sequencing and capillary based electrophoresis.

In brief, the entire workflow of medical resequencing by MPS consists of the following steps:

a) Sample preparation including enrichment (creation of a DNA fragment library or mate paired library)

b) Clone library onto beads using emulsion PCR

c) Deposit bead clones onto slide surface

d) Sequencing clones by either sequencing by synthesis or ligation-based sequencing, simultaneous with imaging

e) Base-calling and downstream data-analysis