Researcher in genetics laboratory

Northern Genetics Service

Clinical genetics

Purpose

Northern Genetics Service (NGS) provides clinical and laboratory genetic services to just over three million people living in Tyne and Wear, Cumbria, Northumberland, County Durham and Teesside from its base at IGM and a satellite unit at the James Cook University Hospital in Middlesbrough.

NGS is a directorate of the Newcastle upon Tyne Hospitals NHS Foundation Trust and is one of 26 regional NHS genetics centres which cover the UK.

The main purpose of NGS is to provide comprehensive, fully integrated, high quality clinical and laboratory services that help reduce morbidity associated with genetic disease. The service aims to provide patients and other health professionals with the information necessary to facilitate decision making by individuals and families who have, or are at risk of, heritable disease.

To achieve this, there is close functional interaction between the sections of the service within the NGS, with other centres around the country and also good communication between genetic services and other relevant clinical specialties.

Background

Over the past 20 years NGS has grown rapidly alongside the other component parts of IGM. From its original home in a terraced house in Newcastle, occupied by a small number of staff, the service expanded during the 1980s and 90s as the clinical importance of genetics became obvious. Initially, the clinical and academic components of the department were almost indistinguishable but, as both grew exponentially, the need for accommodation to meet the different demands of each became obvious. This culminated in the move to IGM in 2001. A fundamental requirement of any new building however was the need for NGS and the University Department of Human Genetics to share the same space - much of the success
of each has been born out of the relationship between the two.

The NGS employs almost 150 people. The team consists of clinical staff who provide clinics in the purpose-built facility within IGM and in hospitals across the region, cytogeneticists identifying pre- and post-natal chromosome abnormalities and cytogenetic variation within tumour cells, and molecular diagnostic scientists searching for DNA variations known to be associated with specific phenotypes. In addition, the NHS staff of the Newcastle Muscle Centre including the Muscle Immunoanalysis Unit are part of NGS. An affiliated laboratory, currently based elsewhere in Newcastle University analyses mitochondrial DNA. All of this work is supported by a group of administrative staff.

The initial academic work of what was to become IGM focused on the identification of genes responsible for rare phenotypes. In pre Human Genome Project days finding even the position of one of these genes was an enormous undertaking. That work was however reliant on the support of clinical staff to identify families in which such analysis would be possible. In return the ultimate identification of these genes dramatically improved the quality of the information that could be provided to these families.

Current Trends

There is an ever increasing demand for genetic services within the NHS. In the last five years alone clinical referrals to our service have increased by over 40%. That inevitably increases the workload for our diagnostic laboratories, both cytogenetic and molecular. At the same time the use of genetic diagnostic tests is becoming increasingly common in other specialties within medicine, further increasing demand on our laboratories. As the governments agenda to ‘Mainstream’ genetics moves forward this demand can only continue to increase. Genetic services will inevitably move from dealing solely with rare disorders caused by mutations in a single gene inherited in a classical Mendelian fashion, to more common disease caused by complex interactions between a number of genes and between genes and the environment. We have already seen the first phase of this with the dramatic expansion of services for patients with, or at risk of, cancer in the last 10 years.

In recent years the component parts of IGM have worked together effectively to apply research findings and techniques originally developed for use in research labs to a diagnostic setting. For example NGS molecular diagnostic staff have worked with IGM scientists who have identified genes responsible for Haemolytic Uraemic syndrome and Cornelia de Lange syndrome, amongst others, to develop tests that can be used to diagnose these conditions in patients in the North East and, through the United Kingdom Genetic Testing Network, across the UK and beyond. We have collaborated to use maldi-tof technology originally developed in a research setting to produce a much more rapid and much cheaper test for Hereditary Haemochromatosis than was previously available.

ChromosomesCytogenetic analysis relies on the ability to identify often extremely subtle rearrangements of chromosome structure. This relies heavily on the skill and perseverance of cytogeneticists. Despite this any abnormality smaller than around 3 megabases will not be visible to standard cytogenetic analysis. Any technique which can improve this resolution will have potential diagnostic significance. In the early 1990s the introduction of Fluorescent In Situ Hybridisation (FISH) was a dramatic step forward. The next revolution, already upon us, is the use of microarray technology to identify cytogenetic abnormalities of clinical significance that are at or below 1 megabase in size and simply impossible to see using standard techniques. At NGS we have piloted this technique and hope to introduce it to diagnostic use within the coming year.

The traditional boundaries between cytogenetic and molecular diagnostic analysis are becoming blurred. We have recognised this by establishing a molecular cytogenetics section within NGS. The use of what are essentially DNA analysis methods such as QF-PCR in prenatal diagnosis of chromosome abnormalities, and MLPA to identifiy specific chromosomal microdeletions requires the skills of both a cytogeneticist and a molecular scientist.

It would be wrong however to believe that NGS staff simply apply the research findings of those working in IGM and other similar academic organisations. High quality research is of great importance in any NHS service and NGS is no exception to that. Such work continues within the clinical service and in the laboratories with significant publications arising from each.

The real challenge that faces NHS genetic services is not whether there will be new research findings that are of relevance in a clinical setting, but how best to move these quickly from a research setting to diagnostic service. The original concept of IGM as a building that would house both research and NHS activity is fundamental in achieving this in a timely and efficient manner. NGS is working with IGM and Life Knowledge Park to develop a system to achieve this.

In the past 20 years NGS and IGM have grown symbiotically to achieve both genetic research and genetic services of the highest quality in the North East of England. The next 20 years will undoubtedly bring changes that will make those we have seen to date pale into insignificance. We are ideally placed to embrace those changes and ensure that the progress that has been made continues and the quality of healthcare that we can provide simply gets better and better.

Senior Personnel

Dr Paul Brennan (Clinical Director)
Mrs Helen Warlow (Directorate Manager)
Dr Rita Barresi (Head of Muscle Immunoanalysis Unit)
Dr David Bourn (Head of Molecular Genetics Laboratory)
Dr Nick Bown (Head of Cytogenetics Laboratory)
Mrs Oonagh Claber
Mrs Lindsay O'dair