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Battle of 2 genes determines mammals' gender, study finds

Two genes lock in a tug of war to determine whether a mammal embryo will become a boy or a girl, a new study suggests.

One of the genes, called Sry, has long been known as the master switch that makes an embryo become male. The new work suggests that a second gene, Dax1, tries to block its effect.It almost always fails. So embryos with one Y chromosome, which carries the Sry gene, and one X chromosome, which carries Dax1, normally develop as males.

But in rare cases, the new study suggests, such embryos get an extra copy of the Dax1 gene. And when two Dax1 genes gang up on the single Sry gene, the competition goes the other way, and the embryo becomes a female.

Dr. Michael Weiss, who studies the genetics of sex determination at the University of Chicago, called the study an important step toward understanding how genes work together to produce either a male or a female.

Understanding the sex-determining pathways, Weiss said, could also shed light on how genes organize themselves to form organs and the immune system. That could lead to new insights into heart disease and rebuilding the battered immune systems of people with AIDS, for example, he said.

The study, done in mice, is reported in Thursday's issue of the journal Nature by Amanda Swain and Robin Lovell-Badge of the Medical Research Council National Institute for Medical Research in London, with colleagues there and elsewhere.

Scientists already believed that the human version of Dax1 was responsible for overcoming Sry in rare cases in which a woman has both genes, plus an extra bit of a second X chromosome. That extra bit contains several genes, including Dax1.