Scientists have identified a genetic reason why boys are significantly more likely than girls to suffer learning difficulties.

A set of nine genes that cause mental retardation when defective has been identified in the biggest genetic investigation of its kind yet conducted.

The rare genetic mutations all lie on the X chromosome leaving males far more likely to be hit.

Women have two copies of the X chromosome and if one carries a mutation in an important gene the other can sometimes provide a back-up. Men, however, have one X chromosome and one Y chromosome, so a mutation in an important X-linked gene will generally have serious adverse effects.

The discovery, by an international team led by British researchers, is a landmark for a new approach to hunting the genetic origins of disease, which focuses on finding rare variations that have significant effects.

Many scientists hope that new technology that allows them to sequence whole genomes quickly and cheaply. They also believe it will uncover many more of these rare variants that influence other serious medical conditions.

The X chromosome study, however, has also illustrated pitfalls with this strategy. It found that about 1 to 2 per cent of the genes on the X chromosome can be knocked out completely without having any biological effects at all. This means that scientists will have to be very cautious about linking rare genetic variations to disease.

Professor Mike Stratton, of the Wellcome Trust Sanger Institute near Cambridge, who led the research, said: “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.”

In the study, which is published in the journal Nature Genetics, Professor Stratton’s team sequenced almost all the X chromosome genes in 208 families affected by learning difficulties. They were then able to sift these for major mutations that might explain why some boys in these families were mentally retarded.

They identified nine new genes that, when knocked out by rare mutations, lead to learning difficulties. “This is the largest sequencing study of complex disease ever reported,” Professor Stratton said.

As the cost of sequencing an entire genome is expected to fall as low as £700 within the next few years, scientists hope soon to adopt the same approach to search for similar rare variations across the entire genetic code.

Lucy Raymond, of the University of Cambridge, who also contributed to the study, said the discovery could have implications for diagnosis of learning difficulties.

“We already offer genetic counselling to families with X-linked learning disabilities,” she said. “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.”

Couples who know they are at risk of passing on a genetic disorder linked to the X chromosome can have their embryos screened to select girls, who are not at risk of developing such conditions.

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