In this WP medical resequencing will be developed for the model disorders hemoglobinopathies and hereditary breast cancer. In these disorders two main loci/genes with many different mutations are involved. The technical aspect of this WP is the development of an enrichment step, based on long-range PCR and on the selector/collector approach, which is feasible for these model diseases.
In this WP, medical resequencing approaches will be developed for sensory disorders. Also generic validation protocols will be developed for technical, analytical and clinical validation of medical resequencing tools. The protocols will be developed in conjunction with EUROGENTEST Unit 5, and will be made available to the participants in other WPs for validation of the medical resequencing approaches. The different kinds of validation have been described in the general outline of the work plan.
In this WP, the feasibility of enrichment by flow through array and/or Array-on-Demand will be assessed. If successful, an initial design of an enrichment array will be developed as prototype. Sequences of genes involved in recessive ataxia will be used for this. Depending on the outcome, an enrichment array for ataxia will be developed. Knowledge and protocols will be transferred to other WPs.
The goal of thisWP is to explore the possibilities of medical resequencing strategies by using MPS technology in the molecular diagnostic analysis of genetic disorders with quite extensive allelic heterogeneity. Also, since copy number variations (CNVs) will also be observed, the aim of this WP includes the development of medical resequencing tools for the analysis of numerical and structural variations. Mental retardation is the model disorder in this WP.
Genetic testing is becoming an integral and growing part of healthcare provision and services. Medical resequencing has the potential to influence medical health care in various ways. It will accelerate the rate of mutation discovery in rare genetic diseases, and also in common diseases with underlying genetic risk factors. It is hoped that molecular diagnostics, prognostics and risk assessment will be improved for individuals. In order to ensure the benefit of such innovations for individuals and society at large it is important to implement human medical genetic testing within an adequate framework of accompanying measures and activities. Quality, trust and confidence should prevail when developing new genetic testing capacities. Because technology is evolving ethical issues have to be re- valuated timely in line with new fields of application.