TECHGENE


General background
Since the sequencing of the human genome has been completed the demand for genetic analysis in the human health care system is drastically increasing, and the extension of molecular genetic diagnostics is urgently needed. However, the majority of genetic diseases is molecularly and clinically highly heterogeneous, and until recently the available techniques lacked the required capacity to analyze several genes in parallel. The recently introduced high-throughput whole genome sequencing (WGS) technology now offers the unique opportunity to extend molecular genetic analysis by introducing these techniques, and develop tailor-made medical resequencing approaches for molecular genetic diagnosis of heterogeneous disorders.

Objective
  • Development of technologies enabling the use of High Throughput Sequencing (HTS) technology for medical resequencing
  • Model design of medical resequencing approaches and proof-of-principle
  • Technical, analytical and clinical validation
  • Achievable turn around time (TAT) of 8 weeks (which is the target for the analysis of large and complex genes, that were imposed by the White Paper of the UK Government in 2003, but which is difficult to reach with the currently used technologies)
  • Acceptable level of cost for a medical resequencing test covering 300 average-sized exons or equivalent
  • Prototype of data analysis software for medical resequencing and assessment of suitability and user-friendliness of the developed data analysis software
  • Outcome of cost effectiveness analysis and the evaluation of the economic impact
  • Guidelines for ethical laboratory practice with regard to high throughput whole genome analysis, technology
  • Knowledge transfer, with special attention to new EU states and associated and candidate states
Project description
The goal of the TECHGENE project is to incorporate the novel HTS technology in routine diagnostic laboratories for the improved diagnosis of genetically heterogeneous diseases. We will develop novel approaches to tailor this novel technology for diagnostic applications in individual patients enabling faster and higher throughput diagnosis of diseases with a genetic component. This technological element offers the opportunity to develop technical products in the field of medical diagnostics that can be exploited by SMEs to be included as future partners. Several SMEs in Europe already are active in this field. They have identified niches in this very competitive field of high throughput molecular technology development and have thus shown that smart innovative activities can complement the mainly genome-wide strategies and products of a number of large companies active in this field. The new technologies that will be developed in the context of this project will also fill in niches by bridging the gap between the current demand for high throughput diagnostics, and the currently offered high throughput technologies, that often lack dedicated applications. This emphasises one of the strategic objectives of this project, i.e. to support and improve the competitiveness of Europe's bioindustry.

New DNA-based technologies compete with other healthcare services for scarce resources but can facilitate more rapid and accurate diagnoses of genetic conditions and predict outcomes for individual patients and potentially prevent disease, prolong life and promote health. It is therefore vital to evaluate the economic impact of introducing new technologies into clinical practice. Rough estimations suggest that the molecular testing of different genes involved in heterogeneous, monogenetic diseases, using the paralleled 'mini-genome per run' approach, will be affordable within the current reimbursement systems in most countries (in other words, the price per test will not exceed the current reimbursement rates for the same diagnosis; this issue will be addressed further in WP6); however, such estimations do not take the potential growth on the multifactorial or pharmacogenetic diseases into account. Clinical validation will initially be performed by application of the techniques in a selection of model hereditary disorders. For these disorders the molecular diagnostic process will be improved. Furthermore, the implementation of the novel technologies in the diagnosis of these genetically heterogeneous model diseases in itself generates invaluable knowledge that will be instrumental in further implementation of molecular diagnostics in other genetically heterogeneous diseases. In addition, this knowledge will be crucial for the development of routine diagnostics for common diseases with several genetic risk factors. The availability of high throughput diagnostics is one of the prerequisites for the development of molecular diagnostics for common diseases. Examples of common disorders with a high heritability are diabetes, Parkinson's disease, and Alzheimer's disease, etc. Many of these common diseases affect older people in particular. The ageing population gives rise to an increase of "old-age" diseases, including those mentioned. This is one of Europe's most formidable societal and healthcare problems. The results and products of this project may therefore be of help in developing strategies to address this healthcare problem, e.g. by enabling early and more accurate diagnosis which can lead to earlier, or even, preventive treatment. Before diagnostics can be performed both in routine genetic diagnostics of common diseases as well as routine pharmacogenetic testing also other barriers have to be overcome, such as gaining of further knowledge of risk factors involved in multifactorial diseases, and the development of robust clinical and economic evidence base for the applications. The availability of better diagnostic protocols will lead to: a) more accurate insight in genotypephenotype correlations, and b) define diagnostic guidelines and recommendations on the basis of the molecular and clinical data. With regards to the development of standards, we will contribute by
(a) The development of validated molecular diagnostic approaches and practical protocols for clinically and/or genetically heterogeneous diseases,
(b) Reducing the turn around times for molecular genetic diagnostics of heterogeneous diseases,
(c) The development of best practice guidelines for model diseases included in TECHGENE, and
(d) The generation of reference materials for model diseases addressed in this project

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