Cambridge (UK) - Researchers from across the world have joined forces to discover nine new genes on the X chromosome that, when knocked out, lead to learning disabilities.
In the five-year study - the largest ever of its type - the international team studied almost all X chromosome genes in 208 families with learning disabilities. Conceived by Dr Lucy Raymond from the University of Cambridge and professor Mike Stratton from the Wellcome Trust Sanger Institute, the collaborative study harnessed DNA sequencing to detect as many new abnormal genes as possible.
Estimates suggest that around two to three per cent of the population suffers from a learning disability. Because it is significantly more common in males than in females, researchers have focused on the X chromosome - males have only one X chromosome and so a gene mutation on the X is more likely to have an effect in males than in females.
One surprising finding was that approximately one to two per cent of X chromosome genes, when knocked out, had no apparent effect on an individual's ability to function in the ordinary world.
"As well as these important new gene discoveries relating to learning disability, we have also uncovered a small proportion - one per cent or more - of X chromosome protein-coding genes that, when knocked out, appear to have no effect on the characteristics of the individual," said professor Stratton. "It is remarkable that so many protein-coding genes can be lost without any apparent effect on an individual's normal existence - this is a surprising result and further research will be necessary in this area."
This finding is actually a bit of a warning for geneticists. Large-scale studies are designed to uncover associations between knocked-out genes and disease. However, if some gene knock-outs have no discernible effect on the individual, researchers will need to be cautious in future about assuming that the presence of a knocked out gene in an individual with a particular disease means that the knocked out gene is causing the disease.
Scientists believe that there are likely to be more undiscovered genes that contribute to X-linked learning disabilities.
The next challenge is to work out what to do with this information in a clinical setting."We already offer genetic counselling to families with X-linked learning disabilities," said Dr Raymond. "This new research uncovers yet more genes that can be incorporated to improve the provision of diagnostics to families with learning disabilities and allow us to develop more comprehensive genetic counselling in the future, allowing parents and the extended family to make the most informed family planning decisions."
In the future, a similar strategy will be used to find disease causing sequence variants implicated in other complex genetic diseases.