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Mapping the sexual divide

July 7, 2006 By Heidi Ledford This article courtesy of Nature News.

Researchers look for genetic clues to disease's gender bias.

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Those who have been keeping a mental tally of the differences between males and females can now add another 25,281 items to the list. That's the number of differences that researchers have found in gene expression between male and female mice, according to a report published online in this month's Genome Research1.

With the exception of sex chromosomes, males and females have all the same genes; although variations in these genes and the genetic material between them produce the different types and amounts of proteins that make one person different from another. Researchers have found that other factors, such as sex hormones, can also affect the amount of protein produced, making gene expression broadly different in males and females. That in turn could affect, for example, the way that drugs are metabolized by men versus women.

A few thousand such differences have been identified before. But now researchers have taken a huge step up in cataloguing the number of genes that behave differently from one sex to the next.

"The results have particular importance for understanding common diseases, almost all of which exhibit some sex bias," says Jake Lusis, a geneticist at the University of California, Los Angeles, and co-author of the study. "For example, women are much more susceptible to most autoimmune diseases, such as lupus and multiple sclerosis, whereas men are more susceptible to heart disease and Alzheimer's disease."

A big surprise

The study revealed the huge extent of sex differences in the genes by surveying more than 1,200 samples of brain, muscle, fat and liver from 334 mice. The team used microarrays to simultaneously assess the expression of more than 23,000 genes in all of the four tissues, looking for differences between the male and female mice. For most genes the expression difference was less than 20%, but for some it was more than 300%.

To their surprise, they found more than 25,000 examples of different gene expression. In the liver, where drugs are metabolised, about 70% of expressed genes were different between the sexes. Only 14% of the genes expressed in the brain were found to be different, although the researchers caution that this preliminary result might not mean anything significant about the difference between male and female brains.

"The striking observation is that the number of genes is much larger than anyone thought," says David Waxman, a biologist from Boston University, Massachusetts, whose lab has previously identified 1,500 examples of sexually biased gene expression in the mouse liver.

Hormonal influence

Thomas Drake, a co-author on the paper and pathologist at the University of California says that other experiments show that these differences are mostly due to the influence of hormones on genes.

The team doesn't yet know what overall difference it makes to the mice for all these genes to be expressed differently. But Lusis, Drake and their collaborators have already used the data to identify regions of the genome that might contribute to mouse obesity, a condition that hits more females than males2.

A greater understanding of these differences, they say, could help to tailor-make drugs for the different sexes.

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References

  1. Yang X., et al. Genome Res., doi:10.1101/gr.5217506 (2006).
  2. Wang ., et al. PloS Genet., 2. e15 (2006).

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