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Last Updated: Wednesday, 16 March 2005, 20:33 GMT
Female chromosome has X factor
By Julianna Kettlewell
BBC News science reporter

X chromosome, Indigo Instruments
The X chromosome can protect females' health. Image courtesy of Indigo Labs.
Females are genetically more varied than males, an analysis of the X chromosome has revealed.

A large team of scientists has published a detailed profile of the DNA bundle in Nature magazine.

They found that female mammals, who possess two copies of the X chromosome, express more genes than males, who only have one X and a Y chromosome.

They also said that females were protected from many diseases because of their double dose of the X chromosome.

"The X chromosome is the most extraordinary in the human genome in terms of biology and its association with disease," said Mark Ross, the project leader at the Wellcome Trust Sanger Institute, UK.

Dwarf Y

The X chromosome - one of 24 distinct chromosomes found in human cells - is much larger than the relatively puny Y, containing 1,098 genes to the Y's 78.

This means that female mammals contain over 1,000 more genes than males. To compensate for this, the female body switches off one X chromosome - quite randomly - in each cell, thus evening up protein production between the sexes.

Tortoiseshell cat, BBC
Tortoiseshell cats have a jumbled expression of X chromosomes
It is this random expression of X chromosomes that accounts for the tortoiseshell cat's distinctive colouring.

Tortoiseshell cats - which are nearly always female - have a gene for one colour on one of their X chromosomes and a gene for another colour on the other X chromosome; and these are expressed in a jumble on the animals' coats, leading to the multicoloured patterning.

However, researchers have recently discovered that the "silent" X chromosome in females is not entirely silent - some of the genes evade inactivation, meaning the fairer sex does actually express more genes than their male counterparts.

"It turns out 15% of genes escape inactivation altogether, each of which now becomes a candidate for explaining differences between men and women," said Robin Lovell-Badge, of the National Institute for Medical Research, UK.

"Moreover, another 10% are sometimes inactivated and sometimes not, giving a mechanism to make women much more genetically variable than men. I always thought they were more interesting!"

Mental retardation

The X chromosome can also protect - or harm - your health, depending on what sex you are.

Although nobody quite knows why the Y chromosome shrank like it did, its decline was not catastrophic thanks to the X chromosome.

X and Y chromosomes, Indigo Instruments
The X chromosome is much larger than the relatively puny Y chromosome
In a sense, it does not matter too much that a male is missing genes on his Y chromosome, because he has equivalent copies on his X chromosome.

But this leaves males vulnerable to any problems lurking on the X.

"Diseases on the X chromosome are usually expressed in males because they don't have a compensating copy of the gene on the second chromosome," said Dr Ross. "More than 300 conditions have been linked to the X chromosome so far."

A host of nasty diseases and disorders sit on the human X chromosome, including haemophilia, autism, muscular dystrophy and mental retardation.

But because females have another - usually healthy - copy of the X chromosome, they are usually shielded from the full impact of these disorders. Males, on the other hand, who have nothing to fall back on, are forced to fully express their faulty genes.

THE DNA MOLECULE
Graphic, BBC
The double-stranded DNA molecule is held together by four chemical components called bases
Adenine (A) bonds with thymine (T); cytosine(C) bonds with guanine (G)
Groupings of these "letters" form the "code of life"; there are about 2.9 billion base-pairs in the human genome wound into 24 distinct bundles, or chromosomes
Written in the DNA are fewer than 30,000 genes which human cells use as starting templates to make proteins; these sophisticated molecules build and maintain our bodies
"Because males have only a single X chromosome, more genetic diseases have been found on this chromosome than any other," said Dr Ian Jackson of the MRC Human Genetics Unit, UK. "One consequence is that boys have a higher incidence of mental retardation than girls.

"The high quality DNA sequence published here has already aided the identification of numerous disease genes. There are many more to be discovered and this sequence will be invaluable for tracking these genes down."

Professor Mike Stratton, of the Wellcome Trust Sanger Institute, said that insights into harmful genes on the X chromosome might allow scientists to intervene to prevent the onset of mental retardation.

"Although it sounds like something of a fantasy, actually there are precedents for it," he said. "So we shouldn't forget that the understanding of these genes may allow us to prevent their onset."

Men also have another reason for feeling upbeat about their genetic lot. New Scientist reports that although men are more likely to be mentally retarded, they are also more likely to be geniuses.

Although the average IQ of men and women is equal, men are more frequently found at both extremes of intelligence.

This is because, if you have very good intelligence genes on your X chromosome, it pays not to have them muffled by more average genes on another X chromosome.




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