Certified Reference Materials for Molecular Genetic Testing - CRMGEN

Project Description

Funding EU 5th Framework; Measurements and Testing RTD Project.
Total Grant: €1185000
Irish allocation: €342000
Coordinator Dr David Barton.
Duration November 1998 - Present.
Collaborators Egbert Bakker (Leiden, Netherlands); Jerzy Bal (Warsaw, Poland); Jean-Jacques Cassiman (Leuven, Belgium); Kyproula Christodoulou (Nicosia, Cyprus); Rob Elles (Manchester, UK); Michel Goossens (Créitil, France); Christoph Klein (Geel, Belgium); Vaidutis Kucinskas (Vilnius, Lithuania); Milan Macek Jr (Prague, Czech Republic); Christine Mannhalter (Vienna, Austria); Clemens Müller (Würzburg, Germany); Glyn Stacey (South Mimms, UK); Su Stenhouse (Newcastle, UK).
Official Website http://www.crmgen.com

Introduction

Molecular genetic tests are used in medicine to identify changes in a patient’s DNA sequence to diagnose or predict an inherited disorder. The tests are highly specific, and thousands of different tests are already in routine use.

Until recently, molecular genetic testing was confined to specialist laboratories with substantial expertise in this area, but such tests are now increasingly being carried out in routine clinical laboratories.

The development of systems to ensure the quality of testing procedures and methods has lagged behind the extremely rapid growth in the application of DNA-based testing in medicine. Concerns over the accuracy of genetic test results are given added importance because individuals are usually only tested once in their lifetime, and the consequences of an incorrect result may be far-reaching.

Public perception currently holds that genetic tests are highly accurate and represent “state of the art” technology. These factors combine to make total quality in molecular genetic testing a matter of primary importance, if a loss of public confidence is not to result.

EU citizens need to know that, regardless of where their test result is obtained, the result will be correct.

The use of appropriate Reference Materials (RMs) to validate test equipment or testing methods is an important part of any analytical testing system. Certified reference materials (CRMs) are RMs whose characteristics have been fully documented and validated. Currently, no CRMs are available for molecular genetic testing.

There are thousands of different molecular genetic tests, each in principle requiring a separate reference material, and new tests become possible all the time due to the advances of the Human Genome Project and related research efforts.

Although tens of RMs will be produced in the course of this project, the main benefit of the project will be the development of the know-how and the methodology to produce CRMs for any given molecular genetic test.

Sources of DNA for use as CRMs will be identified and catalogued. Ethical issues concerning the use of patient samples will be examined. Prototype RMs will be developed for a range of genetic tests, chosen to be representative of a wide spectrum of types of genetic changes.

Most molecular genetic tests are qualitative rather than quantitative - their purpose is to determine the presence or absence of a particular DNA sequence. However, several types of quantitative assay are also used, and reference materials will be of particular practical importance for these tests.

Four basic types of presentations for molecular genetic RMs will be investigated: Cultured cell lines, recombinant (cloned) DNA fragments, enzymatically amplified DNA fragments and genomic DNA.

These prototype RMs, developed in one of four centres, will be validated in five other genetics centres and a reference materials institute before being subjected to extensive field trials in diagnostic molecular genetic laboratories across Europe.

The consortium assembled to tackle this problem is based on existing EU networks for promoting quality in molecular genetic analysis, strengthened by the inclusion of a standards institute with unrivalled knowledge of CRM production and validation.

Allied to these core investigators are several centres of excellence in diagnostic genetics, which will be involved in validating the prototype RMs produced by the core partners.

Six-monthly meetings of the whole consortium will ensure rapid dissemination of information throughout the partnership, with the core laboratories forming the Management Group to steer the project and adjust plans and deadlines as appropriate.

RMs developed in the project will be advanced through the certification process as they become certifiable, leading to the availability of each CRM at the earliest possible moment.

The knowledge gained in this process will be used to develop guidelines for the production of CRMs for any genetic test.

As genetic testing plays an increasingly important role not only in medicine but also in agriculture, food production, forensics and many other areas, the ability to produce CRMs for any genetic test will provide benefits far beyond the boundaries of this current proposal.