The question of whether male homosexuals are gay from birthor from upbringing has long been a hot topic of debate.

One psychoanalytic school of thought, for example, attributes agay man's same-sex preference to the child's bonding with hismother.

Now a just-published DNA linkage study concludes that malehomosexual orientation is, at least in large part and in manyhomosexuals, inherited from the mother via a putative gene inthe X chromosome.

Today's issue of Science carries the report, by researchers atthe National Cancer Institute (NCI), titled "A Linkage BetweenDNA Markers on the X Chromosome and Male SexualOrientation." Its principal author is molecular biologist DeanHamer, who heads gene structure and regulation at NCI'sbiochemistry laboratory.

Why should the National Cancer Institute be probing thegenetic roots of human sexuality? "In part," Hamer explained,"in connection with a study still in progress of possible geneticfactors in various cancers found in high rates in gay men."

The most striking example, he told BioWorld, is Kaposi'ssarcoma, which he said occurs at very high levels in gay menwith AIDS. He sees some evidence that host genetic factors maybe involved, "possibly opening a whole new way of developingtherapeutics for AIDS."

Hamer's gene-seeking DNA linkage-analysis project began byrecruiting 76 self-identified gay men from the outpatient HIVclinic at NCI and from homophile organizations in and aroundWashington, D.C. They, in turn, brought in 46 relatives from 26families -- a total of 122 individuals -- for family pedigreeanalysis.

Families with two gay brothers had a 13.5 percent rate ofhomosexuality, 6.7 times greater than the baseline 2 percent ofincidence in the U.S. population established for the study.

Among relatives, only uncles on the mother's side and the sonsof maternal aunts exceeded the baseline, with a higher-than-expected probability of being homosexual themselves. Fathersand heterosexual paternally related relatives tracked close tothe baseline 2 percent.

These mother-skewed proportions led the investigators toreason that if a gay gene exists, it might well reside on thehuman X chromosome, sole genomic source of exclusivelyfemale nuclear DNA transmission. And the way to close in onthis inferred gene is by DNA linkage analysis, finding patternsof nucleic acid sequences (gene markers) that occursignificantly more often in male homosexuals than in their non-gay relatives.

To find the richest concentration of such markers, presumablyflanking both ends of the presumed gay gene, the NCI teamabout 18 months ago advertised in local and nationalhomophile publications and enlisted 40 pairs of homosexualbrothers.

From this cohort they took peripheral blood, extracted the DNAand probed its strands for matches to 22 markers. They foundthat 64 percent of the siblings tested had clusters of fiveidentical markers within a discrete region on the tip of the Xchromosome's long arm.

This region, Hamer explained, contains some 4 million basepairs, less than 0.2 percent of the human genome's estimated 3billion. That's big enough to harbor several hundred genes, ofwhich a few, such as the ones that code for color blindness andFactor VIII hemophilia, have been mapped.

The reserchers found that five of the 22 polymorphic genemarkers, including simple dinucleotide sequence repeats,variable number of tandem repeats, minisatellites andrestriction fragment length polymorphisms (RFLPs), confirmedmaternal inheritance in 33 of their 40 pairs of gay malesiblings.

A sixth positive marker was ambiguous because it came fromthe extreme tip of the X chromosome, where some nucleic acidmixing with the male-only Y chromosome takes place, implyingalleles from the father as well as the mother.

All of the markers were detected by polymerase chain reaction(PCR) amplification and displayed by electrophoresis.

"If two brothers obtained the same markers from theirmother," Hamer explained, "we scored them as concordant; ifdifferent, discordant. We simply looked for any markers thathad significantly more concordant pairs than discordant."

Confirming the existence of this target stretch of concordantDNA, Hamer tells his Science readers, meant that the gay geneitself must exist. The hunt for it is on.

"It may be a breakthrough, linking for the first time a specificgene with a high-level behavior in the normal human brain,"declared psychiatric geneticist Elliot Gershon, chief of clinicalneurogenetics at the National Institute of Mental Health(NIMH).

"All of us in human behavior today," Gershon told BioWorld,"are looking for genes that affect significant behavior in normalfunction, as opposed to dementia or Huntington's disease ormental retardation." But anent Hamer's study, with which he isfamiliar, Gershon cautioned, "Nothing in this field is convincinguntil it's been independently replicated."

Replication is the buzzword of the hunt for the gay gene, withHamer's Science paper today sounding the tally-ho.

He and his team are already gearing up to replicate as hard asthey can, he told BioWorld: "We are collecting additionalfamilies to repeat our results and make sure they can bereplicated. Also, in order to more precisely map the location ofthe gene or genes themselves, so we can figure out what theycode for."

He added, "Ultimate mapping of the gay gene is essential toseparate the role of inheritance from environmental,experiential, social and cultural factors. DNA linkage studies areonly the first step."

Asked how soon he estimates that gene will be hunted down,Hamer replied, "I would say it should be within six months to20 years."

Does his finding have any bearing on the current debate overgays in the military? "I think the one implication it might have,bearing on that and other debates over gay and lesbian civilrights, is that some people have argued that sexual orientationis merely a choice or decision that people make, and thatbecause they've 'decided' to go against religious dictates, orsocial norms, or whatever, they deserve to be punished.

"Clearly, when you find that something has a geneticcomponent, it indicates that that trait is not purely a choice ordecision, because such people don't decide what genes they'regoing to get."

He concluded with emphasis: "We're not doing this to develop abiotechnology test for who's gay and who's not; I think anysuch application would be unethical."

Gershon concurred. "You're talking about complex inheritance-- something that has a powerful influence on gayness," he toldBioWorld.

"You might end up with a test if you have a gene variant thatincreases the probability of being gay," said Gershon. "You canbe prudishly straight and have that gayness-propensity gene."

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.