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In a study published in the journal Nature Genetics, scientists including University of North Carolina (UNC) biologist Jason Lieb, PhD, (also a member of UNC Lineberger Comprehensive Cancer Center), presents experiments that support a longstanding idea of how males survive with only one copy of the X chromosome.
Their work clarifies a hotly debated topic in science while providing biologists with more information on how to interpret experiments involving genetic measurements in males and females.
"The issue is important because many diseases are tied to defects in regulatory mechanisms within the cell," said Lieb.
Women have two X chromosomes, while men have one X and one Y. The lack of a 'back up' copy of the X chromosome in males contributes to many disorders that have long been observed to occur more often in males. Disorders such as hemophilia, Duchene muscular dystrophy, and certain types of color blindness.
Having only one copy of X and two copies of every other chromosome also creates a more fundamental problem with any other chromosome, the gene number imbalance would be lethal. How can males survive with only one X?
Biologists have been debating how organisms and cells manage the imbalance between X and Y chromosomes for years, with the dominant theory being that both sexes up-regulate (or increase) the expression of X-linked genes, essentially doubling their expression to "2X" in males and "4X" in females.
Then, to correct the imbalance that now appears in females (since they have the equivalent of "4" Xs now and 2 of every other chromosome), females then 'turn off' one of the hyperactive X chromosomes, resulting in a balanced "2X" expression of those genes in both sexes.
The advent of new technology has given scientists more accurate ways to measure gene expression, and some results published in the last few years do not support the idea that X chromosomes up-regulate.
So Lieb and his colleagues re-analyzed data used in previous studies, added findings from new data and found that the up-regulation hypothesis is correct but with some interesting twists across species.
"There are several ways to get the same result and we are seeing how the dosage-balancing mechanism works in different species," says Lieb.
"We also found that not all X-linked genes are dosage compensated to the same degree adding another layer of complexity for scientists who study gene regulation."
Other members of the research team include Christine Disteche, Robert Waterston, Jay Shendure, Di Kim Nguyen, Joseph Hiatt, and Xinxian Ding from the University of Washington; Brian Oliver, and David Sturgill, from the National Institute of Diabetes and Digestive and Kidney Disease, Thomas Gingeras, Carrie Davis, and Felix Schlesinger, from Cold Spring Harbor Laboratory, Valerie Reinke, from Yale University; LaDeana Hillier, from Washington University in St. Louis, and Sevinc Ercan from New York University.
The research was funded by the National Institutes of Health, the William H. Gates III Endowed Chair of Biomedical Sciences at the University of Washington and a fellowship from the Achievement Rewards for College Scientists.
Original article: http://www.med.unc.edu/