High-throughput medical resequencing of candidate disease genes and genomic regions


General background
Diseases like intellectual disability, blindness, deafness and various forms of cancer have extensively been studied in the last decade and many causative and candidate genes and loci for these disorders have been identified. The challenge now is to screen large cohorts of these patients for up to 1000 genes or loci that may harbour causative mutations. Recent advances in sequencing technologies have dramatically increased the speed and throughput capacities of DNA sequencing and, as a corollary, reduced the costs per nucleotide. For most medical applications a targeted analysis of candidate genes or genomic regions is likely to be applied, as this will facilitate functional interpretation of sequence variations and overcome limitations in computational power as well as ethical restrictions.

Objective
This project aims to optimize and apply novel "whole genome" resequencing technology to the study of monogenic diseases with locus heterogeneity.

Approach
In this project apply 2nd generation sequencing to large patient cohorts for two different purposes:
  1. Medical resequencing of candidate genes and genomic loci in monogenic disease
  2. Sequence-based detection and characterization of structural and numerical genomic variations
This project will provide important insight into the power of these novel (re)sequencing strategies for the entire field of human genetics, increase our understanding of the genetics underlying frequently occurring monogenic, but heterogeneous, disorders and will have direct consequences for the future of genetic diagnostics, counselling and clinical management. As the sequencing capacity of this equipment is almost unlimited, we will also offer this technology to other scientists working within the Radboud University Nijmegen Medical Centre and the Radboud University. From the present application it will be clear that a wide range of research lines within these institutes will greatly benefit from the requested equipment. The next generation sequencing technology will allow the various participants to compete successfully in their respective research fields both nationally and internationally.

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