Study Examines Compensatory Up-Regulation of X Chromosome

In a study published online on October 23, 2011 in the journal Nature Genetics, a group of scientists including University of North Carolina (UNC) biologist Dr. Jason Lieb, present experiments supporting a longstanding hypothesis that explains how males can survive with only one copy of the X chromosome. The finding provides clarity to a hotly debated topic in science and provides biologists with more information to interpret experiments involving genetic measurements in males and females. "The issue is important because many diseases are tied to a defect in a regulatory mechanism within the cell," said Dr. Lieb, who is also a member of the UNC Lineberger Comprehensive Cancer Center. 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, 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 resulting from having only one copy 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 other chromosomes for years, with the dominant theory being that both sexes up-regulate 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 (because 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 across both sexes.
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