Authors: Lauren Pulling
As part of our month-long focus on the role of genetics in neurological disorders, we spoke to Oliver Quarrell, a Consultant in Clinical Genetics at Sheffield Children’s NHS Foundation Trust (UK) who treats families with both adult and childhood genetic conditions. Oliver qualified in Medicine in 1980 and obtained his MRCP (UK) qualification in 1984. He was appointed to his current post in 1990 and was elected a Fellow of the Royal College of Physicians in 1994. Oliver is author of ‘Huntington’s Disease: The Facts’, a book aimed at patients and their families, and has also co-edited a book on the juvenile from of Huntington’s as well as a number of papers and book chapters on the disease.
Please could you tell us a little about your background? How did you come to be involved in Huntington’s disease (HD) research?
I did an intercalated BSc during my Medical School years: the project I was given involved working with a group interested in a recessively inherited condition called thalassemia. As a result of that work, I became aware of efforts to clone genes. I did not think about genetics again until 1984 when I was considering an MD. I responded to an advert to work on a project related to the genetics of HD that was based in Cardiff (UK) with Professor Peter Harper. In the previous year the gene for HD had been localized to the tip of the short arm of chromosome 4 in two large families using genetic linkage. My project was to identify large families from the UK and see if they also showed genetic linkage to chromosome 4. The work also allowed me to look at the prevalence of HD and the possibility of predictive testing and pre-natal testing using this technique. Of course, the larger goal was to clone the gene and around that time there was some evidence to suggest that the gene was located at the telomere of chromosome 4. In 1989 I had a travel fellowship to work with Michael Hayden at the University of British Columbia in Vancouver (BC, Canada). It was an interesting year because both the Cardiff and Vancouver groups were able to publish linkage disequilibrium data showing that the gene for HD was located more proximally. In 1990, I completed my training as a Clinical Geneticist but have retained an interest in HD. The gene for HD was cloned in 1993 and both predictive testing and pre-natal testing became easier from the technical perspective, but the genetic counseling issues remain complex because there is still no treatment to alter the natural history of the condition.
We recently featured the review, ‘The global prevalence of Huntington’s disease: a systematic review and discussion’ – could you give our readers a brief overview on the paper?
In the UK we have developed an HD predictive testing consortium, which records annually the number of predictive tests that have been undertaken. We wanted to update the percentage uptake of predictive testing by those at risk for HD. The formula for estimating the number of people at risk for HD in the population requires an estimate of the prevalence of HD; this proved problematic and prompted the systematic review. We chose to look at studies published since the gene for HD was cloned in 1993 because diagnostic testing became easier as a result of that technological change.
There has also been some evidence that the prevalence of HD may be increasing because of an aging population: some genetic changes that are just in the abnormal range may not present until late in life; consequently, as the population ages some of these people may now be diagnosed. In the article we have divided the world into various geographical regions and commented that some of the variation is due to the genetic background of the different populations. Of course, some of the variation is due to the difficulty in ascertaining all the cases in a given population.