In conversation with Claire O'Connell
There are some things that run in families, like red hair and blue eyes. And sometimes medical conditions do to. When that happens, it can be helpful to know what genes are involved, to inform genetic counselling, to develop tests to help diagnosis and possibly even to identify new molecular targets for treatments. Dr Sean Ennis is using genetic techniques to analyse a range of inherited conditions, from relatively common disorders such as autism, to rare diseases that tend to concentrate in families.
New technologies, quicker results
The technology to analyse human genetics has developed rapidly over the last two decades or so, explains Dr Ennis, who is a Lecturer at UCD School of Medicine & Medical Science and a Principal Investigator at the National Centre for Genetics in Crumlin.
There was a time when if you wanted to work out the mutations, or changes in DNA, that were linked to an inherited disease, you would get samples from the patients, analyse them and then put them in the freezer and wait for the next generation to be born so you could continue the study,” he says.
Times have moved on, he notes, and now approaches such as exome sequencing, which works out the ‘letters’ in DNA that encode genes, and other techniques offer the chance to find important mutations more rapidly.
Autism - genetic complexity
For many years, Dr Ennis has been working on the genetics of autism with colleagues in TCD, Ireland and internationally. One of their major breakthroughs was to highlight the complex nature of mutations in the condition - by genotyping 9,000 individuals in 3,000 families and looking to see whether there were common changes in the DNA letters that were linked with autism. The results were surprising, and they changed the thinking about autism genetics, explains Dr Ennis.
Prior to that study it was thought there were a few common genes involved in autism,” he says. “But our data showed that there wasn’t, that instead there were multiple rare variants.”
Rare diseases - the genetic link
While Dr Ennis remains involved in autism research, he and colleagues at UCD have also developed a particular strength in investigating the genetics of inherited rare diseases. By their nature, individual cases rare diseases may not be numerous, but the sheer numbers in the rare disease category quickly add up, and most have a strong genetic component, he explains. “There are about 6,000 to 8,000 known rare diseases, and about 80 per cent of them are genetic in background.”
Because many of those rare diseases tend to involve a small number of key genes and are concentrated in families, it can make the hunt for participating genes and mutations more directed, explains Dr Ennis.
And at UCD there is considerable interest in finding out more about inherited rare diseases among the Traveller community in Ireland, he adds. “We reckon there are around 60 genetic conditions associated with the Traveller community here, and we are looking at some of these conditions.”
An eye to diagnosis
They have already had considerable success. One breakthrough was in a rare disease called micro-anophthalmia, where children are born with eyes that are small or missing. One family had seven affected members, so the researchers, including Dr Jillian Casey, compared at genetic information from affected people and their close relatives and homed in on a relatively small stretch of DNA that contained two genes of interest.
One of those genes was STRA6, which in involved in vitamin A uptake, an important factor in eye development, and the UCD/Crumlin study showed that mutated STRA6 was at the root of micro-anophthalmia. The findings led to the development of a service test that can be used to inform genetic counselling for potentially affected families.
That’s just one of several examples where, by focusing on a rare disease in related groups, UCD research has unveiled important genetic information about rare conditions, and Dr Ennis points out that knowing about these key molecular events can lead to better diagnostic tests and, in the longer term, could possibly inform new approaches to treatment.
Rare Diseases Centre
He now wants to consolidate the ongoing work in rare diseases through a proposed new Rare Diseases Centre, which would harness the expertise that has grown organically in UCD, Crumlin and the Children’s University Hospital at Temple Street in recent years.
My aim in terms of rare diseases is to take it beyond individual investigators,” he says.
The study of rare diseases is bringing together clinicians, geneticists, experts in animal models and others who are in position to translate findings into to the clinic. We want to get the research in a more established framework so we can look for longer-term funding and build strategies around rare diseases.
Editors note: the Centre gained formal status in Summer 2013.