Women are from Venus, men are from Mars? Apparently it is not the planet (or genome) that differs, but how our global genome is expressed.
UCLA researchers report in a new study that thousands of genes behave differently in the same organs of males and females—something never detected to this degree. The study, published in the August issue of the journal Genome Research, sheds light on why the same disease often strikes males and females differently, and why the genders may respond differently to the same drug.
The UCLA team examined brain, liver, fat and muscle tissue from mice, with the goal of finding genetic clues related to mental illnesses, diabetes, obesity and atherosclerosis. Humans and mice share 99 percent of their genes.
With the help of genomic-research company Rosetta Inpharmatics, the team scrutinized more than 23,000 genes to measure their expression level in male and female tissue.
What they found was surprising. While the function of each gene was the same in both sexes, there was a direct correlation between gender and the amount of gene expressed.
"We saw striking and measurable differences in more than half of the genes' expression patterns between males and females," said Dr. Thomas Drake, co-investigator and UCLA professor of pathology. "We didn't expect that. No one has previously demonstrated this genetic gender gap at such high levels."
UCLA is the first to uncover a gender difference in gene expression in fat and muscle tissue. Earlier studies have identified roughly 1,000 sex-biased genes in the liver, and other research has found a combined total of 60 gender-influenced genes in the brain—about one-tenth of what the UCLA team discovered in these organs.
Even within the same organ, researchers identified scores of genes that varied in expression levels between the sexes. Gender consistently influenced the expression levels of thousands of genes in the liver, fat and muscle tissue. This effect was slightly more limited in the brain, where hundreds—not thousands—of genes showed different expression patterns.
The gender differences in gene expression also varied by tissue. Affected genes were typically those most involved in the organ's function, suggesting that gender influences the more important genes with specialized roles, not the rank-and-file.
In the liver, for example, the expression of genes involved in drug metabolism differed among men and women. The findings imply that male and female livers function the same but work at different rates.
"Our findings in the liver may explain why men and women respond differently to the same drug," Lusis said. "Studies show that aspirin is more effective at preventing heart attack in men than women. One gender may metabolize the drug faster, leaving too little of the medication in the system to produce an effect."
The UCLA findings support the importance of gender-specific clinical trials. Most medication dosages for women have been based on clinical trials primarily conducted on men.
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