Roanoke Times
                 Copyright (c) 1995, Landmark Communications, Inc.

DATE: THURSDAY, July 19, 1990                   TAG: 9007190345
SECTION: NATIONAL/INTERNATIONAL                    PAGE: A-2   EDITION: STATE 
SOURCE: The Washington Post
DATELINE:                                 LENGTH: Medium

SCIENTISTS DISCOVER WHAT GENE IT TAKES TO BE A MAN

In a paper published in today's issue of the scientific journal Nature, a group of British scientists reports that it has identified a single gene that appears to set in motion a cascade of events that turn a fertilized egg into a male. In the absence of the gene, researchers say, the embryo would become female.

The findings are not yet conclusive. According to the scientists who conducted the research, final proof awaits the outcome of experiments on mice. In addition, another paper published in the same issue of Nature suggests that there is some evidence that two or three other genes may be necessary for fully normal maleness.

But after 30 years of intensive detective work by geneticists, the gene appears to be the most promising candidate ever discovered to account for the anatomical and perhaps even some behavioral differences between the sexes. By better explaining the determinants of human development, it also appears to open the door to better understanding and perhaps treatment of some causes of infertility.

The researchers named the gene SRY, for "Sex-determining Region of the Y chromosome." The Y chromosome and the X chromosome have long been known to contain the gene or genes that determine sex. Females have two X chromosomes. Males have one X and one Y.

Although the presence of the Y chromosome is clearly the factor that differentiates a man from a woman, not all of the genes that lie on it are involved in determining sex. As early as 1966, for example, scientists had found men who had two X chromosomes, with a tiny portion of a Y chromosome attached to one of their Xs. These individuals who look and function as men possessed just one half of one percent of the genes that normally lie on the Y chromosome.

What this showed was that the trigger that determines whether an embryo is male or female must lie within that tiny part of the Y carried by XX males.

In the current issue of Nature, two teams of London researchers led by Andrew H. Sinclair and Robin Lovell-Badge argue that the culprit is the SRY gene. Their evidence comes from mice, whose sex is determined by X and Y chromosomes very similar to those of humans. SRY, the researchers found, is activated in mice at just the time when the development of male and female mouse embryos diverges on to different paths.

The researchers also had the good fortune to find a mouse with both an X and Y chromosome that, because of a mutation, lacked the critical SRY gene. The XY combination meant it should have been a male, but it was a female.

Another paper published in Nature also urges caution in accepting the SRY gene as sufficient to cause normal maleness. David Page, a geneticist at the Whitehead Institute in Cambridge, Mass., who announced in 1987 that he might have found the maleness gene but was proven wrong, cites previous research that more than one gene may be needed. Page says the research shows that XX humans who also carry a tiny snippet of the Y containing the SRY gene but little else were only ambiguously male, lacking, for example, fully developed male genitalia and carrying some ovarian tissue.