A study by geneticist Dean Hamer proposed that Xq28, a region of the X Sex Chromosome, might play a role in determining whether a man was gay. This idea was suggested more than 20 years ago, the study first being published in 1993.“When you first find something out of the entire genome, you’re always wondering if it was just by chance,” Hamer told Science of the new study, adding that the research “clarifies the matter absolutely.” Although the 1993 researchers only studied 38 pairs of brothers, Hamer told New Scientist that he sees the new paper as confirmation of his work. “Twenty years is a long time to wait for validation, but now it’s clear the original results were right,” he said. “It’s very nice to see it confirmed” (Grant).
Hamer’s study was quite small back in 1993, but he helped pave the way for other scientist to continue work on these chromosomes. For instance, the latest study involves about three times as many people as the previous largest study, which means it is significantly more statistically robust. The study leader, Alan Sanders, says that his study “erodes the notion that sexual orientation is a choice” (Coghlan).
Over the past five years, Sanders has collected blood and saliva samples from 409 pairs of gay brothers, including non-identical twins, from 384 families. This compares, with 40 pairs of brothers recruited for Hamer’s study. Sanders team combed through the samples that was obtained, looking at the locations of genetic markers called single nucleotide polymorphisms (SNPs). Which are the differences of a single letter in genetic code; and measured the extent to which each of the SNPs were shared by the men in the study. Only five SNPs stood out and of those, the Xq28 and 8q12 regions on the X chromosome and chromosome 8 respectively, were the most commonly shared between the men (Coghlan).
Although, this doesn’t mean the study found two “gay genes”. Both regions contain many genes, and the next step for researchers will be to determine which ones might be contributing to sexual orientation. Sanders says that he has already completed the work for that next step: he has compared the SNPs in those specific regions in gay and straight men to see if there are obvious differences in the gene variants, and is now preparing the results for publication. “Through this study, we have the potential to narrow down to fewer genes,” says Sanders (Coghlan).
Although these twin studies suggested, that gene sequences can’t be the full explanation. For example, the identical twin of a gay man, despite having the same genome, only has a 20% to 50% chance of being gay himself (Balter). This is why some scientists are suggesting that epi-marks might also be involved with determining sexuality.
This is why evolutionary geneticist William Rice had done a study back in 2012 on epi-marks. Epi-marks are molecular changes that act like temporary “switches” to turn genes on and off. If a gene is a blueprint, the epi-mark is the construction foreman who makes sure the product gets built. An epi-mark also determines when, where and how much a gene is expressed, according to the National Institute for Mathematical and Biological Synthesis (Pappas).
Rice uses the term epi-marks to denote changes in chromatin structure that influence the transcription rate of genes (coding and noncoding such as miRNAs), including nucleosome repositioning, DNA methylation, and/or modification of histone tails, but not including changes in DNA sequence (Rice). His study “examines the ramifications of transgenerational (which is “having an effect on several generations of a family” as defined by Medical Dictionary.) epigenetic inheritance to the phenomenon of human homosexality.” It provides clear evidence that environmentally induced epigenetic modifications of genes expressed in male mice that feminize their brains and behavior can be transgenerationally inherited by their offspring (Rice).
This idea inspired Tuck Ngun, a postdoc in Eric Vilain’s lab, to study the methylation (an epigenetic mechanism used by cells to control gene expression.) patterns at 140,000 regions in the DNA of 37 pairs of male identical twins who were discordant — meaning that one was gay and the other straight — and 10 pairs who were both gay. After several rounds of analysis — with the help of a specially developed machine-learning algorithm — the team identified five regions in the genome where the methylation pattern appears very closely linked to sexual orientation. To test how important the five regions are, the team divided the discordant twin pairs into two groups. They looked at the associations between specific epi-marks and sexual orientation in one group, then tested how well those results could predict sexual orientation in the second group. They were able to reach almost 70% accuracy, although the presentation makes clear that—in contrast to what a provocative ASHG press release about the study suggested—this predictive ability applies only to the study sample and not to the wider population (Balter).
Just why identical twins sometimes end up with different methylation patterns isn’t clear. If Rice’s hypothesis is right, their mothers’ epi-marks might have been erased in one son, but not the other; or perhaps neither inherited any marks but one of them picked them up in the womb. In an earlier review, Ngun and Vilain cited evidence that methylation may be determined by subtle differences in the environment each fetus experiences during gestation, such as their exact locations within the womb and how much of the maternal blood supply each receives (Balter).