X chromosome again linked to homosexuality.

In a reprise of the most controversial study of 1993, researchers surveying the genetic landscape of the X chromosome have discovered further evidence that it contains a gene or genes that may steer some men to homosexuality.

"Once again, we've found that more than half of gay brothers share the same chromosome region. It gives us additional confidence that there is something in this region involved in sexual orientation," says Dean H. Hamer of the National Cancer Institute in Bethesda, Md.

Two years ago, Hamer reported that men might inherit a predisposition to homosexuality through the X chromosome, whose genes are passed on by mothers (SN: 7/17/93, p.37). Some scientists harshly criticized the study, as well as the general effort to probe the genetics of behavior. This summer, the Chicago Tribune reported that a former member of Hamer's group had raised questions about how Hamer conducted the 1993 study, prompting a still-ongoing inquiry by the Department of Health and Human Services.

In the new study, as in the original, Hamer and his coworkers examined the X chromosomes of families that have two homosexual brothers. Since a son can inherit parts of his X chromosome from either of the two versions his mother has, the investigators looked for genetic markers, brief sequences of DNA, that differ between the two maternal X chromosomes.

Two-thirds of the 32 pairs of homosexual brothers included in the final analysis share the same markers for one portion of their X chromosome and thus inherited the same span, Hamer and his colleagues at the University of Colorado in Boulder and the Whitehead Institute for Biomedical Research in Cambridge, Mass., report in the November Nature Genetics.

Ordinarily, if that region played no role in sexual orientation, says Hamer, only about half the brothers would share it.

In another test, which Hamer had been chastised for not doing in the 1993 study, investigators examined the X chromosomes of heterosexual brothers of the homosexual men. At most, one-fourth of the 12 heterosexual brothers have the chromosome X region that their homosexual brothers share--less than the expected one-half, says Hamer.

Investigators also inspected the X chromosomes of 36 pairs of lesbian sisters but found no evidence that the chromosomes contain genes affecting the women's sexual orientation. "To me, it's not a surprise, because the pathways leading to female and male sexual orientation are probably quite different," says Hamer.

The researchers stress that the so-called gay gene on chromosome X would be neither sufficient nor necessary to make a man homosexual. Some heterosexual brothers possess the suspect region, while some homosexual men do not. "This gene is not acting like some automatic switch that makes you one way or the other," says Hamer.

The new study is not likely to settle whether the X chromosome holds a gene that sways sexual orientation. "It certainly falls short of a replication, considering it doesn't come from an independent team," says George C. Ebers of the University of Western Ontario in London.

Ebers' own, not-yet-published genetic analysis of homosexual brothers does not show any evidence of a gay gene on the X chromosome. "I don't have any explanation for why we differ," he says. Similar studies by other investigators are already under way.

"This issue won't be resolved by picking apart Hamer's studies. It will be resolved by doing a larger, definitive study," comments J. Michael Bailey of Northwestern University in Evanston, Ill., whose studies of twins have suggested that genetics does influence an individual's sexual orientation.