SRY and sex reversal 9/10/03. By Giles Newton It can come as a shock for a man to find out that he lacks a Y chromosome, and is an XX male. Or indeed for a woman to discover she is an XY female. Such cases highlight the impact of the SRY gene.

For SRY is the ultimate 'maleness gene': action of the gene about six weeks after conception triggers the formation of the testes. The testes subsequently make testosterone which floods through the body, making it male. Without a Y chromosome and hence an SRY gene, a fetus would develop the default gender, which is female. Indeed, a genetic test for SRY was used to ensure that potential competitors for the women's Olympic events in Atlanta really were females.

SRY is the ultimate 'maleness gene': action of the gene about six weeks after conception triggers the formation of the testes.

Even if people have an X and a Y chromosome, they can develop into females if they have a mutation in the SRY gene, or in one of the other sex-determining genes downstream of SRY in the pathway of male sex determination. But if the SRY gene is transferred to the X chromosome during the production of sperm, an XX male can result.

"XX males come about through a lot of different mechanisms," says Mark Jobling, "but we're interested in the translocation of SRY because it involves recombination between the X and the Y chromosomes." The key genes are called PRKX on the X and PRKY on the Y, and their sequences are so similar that they can pair up during sperm production. If the recombination machinery gets confused, the SRY gene can be shunted across to the X chromosome.

As in his studies of the AZFa region, Dr Jobling is examining the frequency and type of these translocation events in the sperm of fertile men. "We'll also find the reciprocal of the SRY translocation," he says. "When SRY goes across to the X, some X chromosome material must go across to the Y chromosome, potentially giving rise to XY females. But we rarely find these in the general population, presumably because they don't survive well in the uterus."

Feature: Inside infertility

Not all males can produce XX male sons in this manner, however. In most Europeans, the PRKY gene is flipped around so that it cannot line up with PRKX and recombination is unlikely. "Almost all these XX males come from the rarer Y group," says Dr Jobling. "So we not only have a mechanism to study, we also have a population effect."