UCLA researchers report that thousands of genes behave differently in the same organs of males and females – something never detected to this degree. Published in the August issue of Genome Research, the study sheds light on why the same disease often strikes males and females differently, and why the genders may respond differently to the same drug.
"We previously had no good understanding of why the sexes vary in their relationship to different diseases," explained Xia Yang, Ph.D., first author and postdoctoral fellow in cardiology at the David Geffen School of Medicine at UCLA. "Our study discovered a genetic disparity that may explain why males and females diverge in terms of disease risk, rate and severity."
"This research holds important implications for understanding disorders such as diabetes, heart disease and obesity, and identifies targets for the development of gender-specific therapies," said Jake Lusis, Ph.D., co-investigator and UCLA professor of human genetics.
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.
The scientists focused on gene expression -- the process by which a gene's DNA sequence is converted into cellular proteins. With the help of Rosetta Informatics, the team scrutinized more than 23,000 genes to measure their expression level in male and female tissue.
What they found surprised them. While each gene functioned the same in both sexes, the scientists found 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 in the same organ, the 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.
"Males and females share the same genetic code, but our findings imply that gender regulates how quickly the body can convert DNA to proteins," said Yang. "This suggests that gender influences how disease develops."
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 important genes with specialized roles, not the rank-and-file.
In the liver, for example, the expression of genes involved in drug metabolism differed by sex. 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," noted Lusis. "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."
"At the genetic level, the only difference between the genders is the sex chromosomes," said Drake. "Out of the more than 30,000 genes that make up the human genome, the X and Y chromosomes account for less than 2 percent of the body's genes. But when we looked at the gene expression in these four tissues, more than half of the genes differed significantly between the sexes. The differences were not related to reproductive systems – they were visible across the board and related to primary functions of a wide variety of organs."
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.
"This research represents a significant step forward in deepening our understanding of gender-based differences in medicine," said Dr. Janet Pregler, director of the Iris Cantor-UCLA Women's Health Center. The center's executive advisory board, a group of businesswomen interested in advancing women's health, helped fund the study.
"Many of the genes we identified relate to processes that influence common diseases," said Yang. "This is crucial, because once we understand the gender gap in these disease mechanisms, we can create new strategies for designing and testing new sex-specific drugs."
Elaine Schmidt | EurekAlert!
Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie
Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy