Peter Schattner, author of "Sex, Love and DNA," likes to tell this true story to illustrate how assumptions about gender don't always hold: "Mario" (not his real name), a perfectly healthy man, went to the doctor wondering why he and his wife weren't getting pregnant. The doctor concluded that his sperm count was zero, and follow-up appointments eventually revealed that he had two X chromosomes.
"It's quite rare, but it's hardly unique," Schattner said.
How can this happen? The short answer, Schattner said, has to do with a sex-determining gene on the Y chromosome called SRY.
"Usually the SRY protein – which is produced from the SRY gene - initiates the male sexual-development pathway; without SRY protein, the developing embryo progresses as a female," he said.
"This is just the first piece of the puzzle, though. SRY is simply a regulator protein that controls what other proteins in the sexual-development pathway are produced.
One of the most important of these is called SOX9. SOX9 is not located on the Y chromosome and is the key to why Mario is male. Mario had inherited a rare mutation that altered the regulation of SOX9 so that Mario's cells produced SOX9 continuously, whether or not SRY protein was present. Consequently Mario became a man, even though he had no Y chromosome."
And, because hormones also play a role in determining sex, people with "male" XY or "female" XX genes can also be intersex. In people with XX genes and a condition called congenital adrenal hyperplasia, for example, the adrenal glands produce testosterone instead of cortisol, sometimes resulting in ambiguous genitalia.
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