X- Chromosome and Autism etc.

Sex chromosome clue to autism
17:46 09 September 2003
NewScientist.com news service

A small group of genes on the X chromosome regulate the brain's "threat-detector" and might explain the high prevalence of autism among males, researchers have discovered.

Some people lacking these genes have problems recognising fear in another person's face, a common trait in autism. They also have abnormal amygdalas - a brain area known as the "fear centre".

The results provide a possible genetic mechanism for the sex bias of autism. Other recent research has identified a gene in the same region of the X chromosome that correlates with the severity of autism. However, confirmation of this explanation of autism's sex bias is still far off - researchers have not yet determined which specific gene or genes are responsible and have not looked at the function of these genes in autistic people.

Previous research suggests autism has a genetic basis, but so far, no single gene has been located that causes the disease in the general population. Autism is 10 times more prevalent among boys than girls, suggesting that a genetic factor may be sex-linked.

"The answer must lie in the sex chromosome," said David Skuse, from the Institute of Child Health in London, speaking at the British Association Festival of Science in Salford, near Manchester, UK, on Tuesday.

Double X
The X chromosome carries many genes that are vital for a wide range of physiological functions. Women have two X chromosomes while men have an X and a Y. Because almost all women have two copies of X chromosome genes, their cells turn off, or inactivate, one copy.

However, not all X-linked genes undergo this inactivation, meaning that women could have higher levels of some gene products in their cells. Skuse suggests it is these "dosage-sensitive" genes that are responsible for the sex differences in autism.

Skuse and his colleagues studied women with only one X chromosome, a condition known as Turner's syndrome. These women are susceptible to problems with X-linked genes just like men and are much more likely to develop autism than unaffected people.

In fact, both autistic people and women with Turner's syndrome share a common trait - they avoid eye contact and have trouble reading fear in another person's facial expression. These problems can also be observed in the brain, says Skuse, as both groups show abnormalities in the function of the amygdala and its cortical connections.

The team narrowed down the section of the X chromosome responsible for these problems by looking for women missing just a small part of one of their Xs, but who also have trouble recognising fear. This left three or four gene candidates and Skuse hopes that, once they identify a specific gene, they will be able to look directly at its function.

Journal reference: Brain (vol 126, p 1)