The Gene: An Intimate History - Siddhartha Mukherjee Page 0,175

elaborate family trees to determine if sexual orientation ran in families, to describe the pattern of its inheritance, and to map the gene. But mapping the gay gene, Hamer knew, would become vastly easier if he could find brother pairs where both were known to be gay. Twins share the same genes, but brothers share only some sections of their genomes. If Hamer could find brothers who were gay, he would find the subsections of the genome shared by them, and thereby isolate the gay gene. Beyond family trees, then, Hamer needed samples of genes from such brothers. His budget allowed him to fly such siblings to Washington and provide a $45 stipend for a weekend. The brothers, often estranged, got a reunion. Hamer got a tube of blood.

By the late summer of 1992, Hamer had collected information about nearly one thousand family members and built family trees for each of the 114 gay men. In June, he sat down for the first glimpse of the data on his computer. Almost instantly, he felt the gratifying heave of validation: as with the Bailey study, the siblings in Hamer’s study had a higher concordance in sexual orientation—about 20 percent, nearly twice the population rate of about 10 percent. The study had produced real data—but the gratification soon turned cold. As Hamer pored through the numbers, he could find no other insight. Beyond the concordance between gay siblings, he found no obvious pattern or trend.

Hamer was devastated. He tried organizing the numbers into groups and subgroups, but to no avail. He was about to throw the family trees, sketched on pieces of paper, back into their piles, when he stumbled on a pattern—an observation so subtle that only the human eye could have discerned it. By chance, while drawing the trees, he had placed the paternal relatives on the left, and maternal relatives on the right, for each family. Gay men were marked with red. And as he shuffled the papers, he instinctively discerned a trend: the red marks tended to cluster toward the right, while the unmarked men tended to cluster to the left. Gay men tended to have gay uncles—but only on the maternal side. The more Hamer hunted up and down the family trees for gay relatives—a “gay Roots project,” as he called it—the more the trend intensified. Maternal cousins had higher rates of concordance—but not paternal cousins. Maternal cousins through aunts tended to have higher concordance than any other cousins.

The pattern ran generation on generation. To a seasoned geneticist, this trend meant the gay gene had to be carried on the X chromosome. Hamer could almost see it now in his mind’s eye—an inherited element passing between generations like a shadowy presence, nowhere as penetrant as the typical cystic fibrosis or Huntington’s gene mutations, but inevitably tracking the trail of the X chromosome. In a typical family tree, a great-uncle might be identified as potentially gay. (Family histories were often vague. The historical closet was substantially darker than the current sexual closet—but Hamer had collected data from occasional families where sexual identity was known for up to two or even three generations.) All the sons born from that uncle’s brothers were straight—men do not pass on the X chromosome to their children (sperm, remember, carries only the Y chromosome). But one of his sister’s sons might be gay, and that son’s sister’s son might also be gay: a man shares parts of his X chromosome with his sister and with his sister’s sons. And so forth: great-uncle, uncle, eldest nephew, nephew’s sibling, sidestepping through generations, forward and across, like a knight’s move in chess. Hamer had suddenly moved from a phenotype (sexual preference) to a potential location on a chromosome—a genotype. He had not identified the gay gene—but he had proved that a piece of DNA associated with sexual orientation could be physically mapped to the human genome.

But where on the X chromosome? Hamer now turned to forty gay sibling pairs from whom he had collected blood. Assume, for a moment, that the gay gene is indeed located on some small stretch of the X chromosome. Wherever the stretch is, the forty siblings would tend to share that particular chunk of DNA at a significantly higher frequency than siblings where one is gay and the other straight. Using signposts along the genome defined by the Human Genome Project, and careful mathematical analysis, Hamer began to sequentially narrow the stretch to shorter and shorter regions of the X chromosome.