Large-scale study identifies new genes involved in mental retardation
In one of the largest genetic sequencing efforts of a complex disease, an international team of partly EU-funded scientists has identified nine new genes on the X chromosome that play a role in learning disabilities. Their inactivation will lead to mental retardation. The study has been published in the journal Nature Genetics. Mental retardation is defined as a disability that leads to significant limitations in intellectual functioning and a lack of conceptual, social or practical adaptive skills. The symptoms appear before the age of 18. This kind of disability is more common in males than in females and has hence it long been thought to be linked to the X chromosome: As males only have one X chromosome, a genetic mutation on the X chromosome is more likely to have an effect, since they do not have a second X chromosome to compensate for the mutation. To learn more about X-linked mental retardation (XLMR), the scientists, partly supported by the EU-funded projects GEN2PHEN ('Genotype-to-phenotype databases: a holistic solution') and EURO-MRX ('The genetic and neurobiological basis of X-linked mental retardation'), sequenced 720 out of approximately 800 known genes on the X chromosome in more than 200 families affected by X-linked learning disabilities from the UK, the US, Australia, Europe and South Africa. So far, a total of approximately 80 genes involved in XLMR have been identified with the help of genetic sequencing techniques. The discovery of these new genes will help improve clinical practice and counselling offered to families with X-linked learning disabilities. Dr Lucy Raymond of the Cambridge Institute for Medical Research at the University of Cambridge, UK, says: 'This new research uncovers yet more genes that can be incorporated to improve the provision of diagnostics to families with learning difficulties 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.' However, the study provides additional insights: 'As well as these important new gene discoveries relating to learning disability, we have also uncovered a small proportion - 1% or more - of X chromosome protein-coding genes that, when knocked out, appear to have no effect on the characteristics of the individual,' states Prof. 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.' The scientists point out that this should be a warning to geneticists: if some gene knock-outs have no discernible effect on the individual, researchers should be careful in assuming that the presence of a knocked-out gene in a patient means that there is a link between the disease and the gene in question.