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Genes behind transsexualism possibly found

May 11, 2005

http://www.world-science.net/exclusives/050511_transfrm.htm

Special to World Science

Scientists say they may have found genes that help explain why a tiny percentage of men see themselves as women, cruelly trapped in the wrong body.

 

A famous  transsexual, Christine Jorgensen (1927-1989), born George, who obtained a sex change operation in 1952 in Denmark.


The researchers say the findings are very preliminary and should be “interpreted with the utmost caution,” due to the small sample size used in their study.

 Nonetheless, they say, the results might shed some light on the rare condition, transsexualism. It is estimated to afflict about one in 30,000 men, some of whom follow through on their sense of their correct gender by getting sex-change operations.

More broadly, the research could help clarify one of the most contentious and poorly understood questions in biology: what creates “gender identity”—the sense most people have that they are either a man or a woman. 

The feeling is normally rather deep-seated; people don’t need to examine their body shapes to confirm it. It is also considered distinct from the issue of whom a person is sexually attracted to.

The question is how genes, culture or both conspire to produce gender identity.

Transsexualism “raises important questions as to how the gender identity is moulded in humans,” wrote the researchers, who included Susanne Hennigsson of Göteborg University and Mikael Landén of the the Karolinska Institute in Göteborg and Stockholm, Sweden, respectively. 

They describe the research in the August issue of the scientific journal Psychoneuroendocrinology

If their findings are correct, the risk of becoming a transsexual may depend partly on variations in the length of certain segments of DNA where the genetic code “stutters,” that is, a few “letters” of the code repeat themselves in the same order many times.

Notably, scientists found in a study published last December that these repeat sequences may be the sites of some of the most common genetic mutations, and thus may underlie some of the fastest evolutionary changes in life’s history. Evolutionary theory holds that mutations produce evolution, because the occasional mutations that are advantageous spread through populations, changing these populations’ characteristics, and over time gradually create new species. 

In that study of last year, researchers found that the muzzle length of dogs depends on the length of certain repeat sequences.

In the transsexualism study, the researchers examined a repeat sequence in each of three genes known to affect the sexual development of the brain, in hopes that one or more of these might shed light on transsexualism. They studied several common variants affecting the length of these repeats in different people. 

These variants “are all much more common than is transsexualism” itself, they wrote. “Hence, the goal of this study was not to reveal the primary cause of transsexualism,” but rather to help explain “whether the studied genes may facilitate or prevent” it.

One particular variant seemed significantly associated with the frequency of transsexualism, they found. This variant was in a gene responsible for producing a molecule called ER-Beta. ER-Beta acts as a minuscule gateway that controls the flow of estrogen, a hormone, through the brain during fetal development. 

Estrogen is thought to be responsible for wiring the brain in a “masculine” way in males before birth—although, paradoxically, the substance is better known as a female sex hormone. This is because after birth, it influences the development of female sexual characteristics.

The gene that produces the ER-beta receptor contains a section called a CA repeat sequence, so called because C and A are names for two “letters” of the genetic code which, here, are repeated many times in a row. 

The researchers found that longer CA repeats were associated with a greater risk of transsexualism in the the study, which included 29 male-to-female transsexuals (men who wish they were women) and 229 healthy males.

It is unknown exactly how this change in the ER-beta gene might contribute to transsexualism, the researchers said. The gene may produce different variants of the molecular gateway, which transmit estrogen more or less easily; but it’s unknown whether one of these might be the reason for the effect, or whether the reason is something else.

Moreover, the researchers found that the two other genes that they studied also seem to influence the risk of becoming a transsexual. But neither of these genes on its own predicted that risk, they found. Rather, specific combinations of all three variants seemed to be more common among transsexuals.

The other two genes studied were genes encoding the production of molecules called aromatase and androgen receptor. These genes, too, are believed to help determine how “masculine” the brain becomes.

More masculine, in this context, means that certain brain structures are relatively smaller or larger in males than in females, possibly reflecting the relative importance of those brain structures in each sex. 

Researchers have found that parts of the frontal cortex, the seat of many reasoning functions, and the limbic cortex, involved in emotions, are bigger compared to other brain areas in women than in men. Parts of the parietal cortex, which contributes to spatial perception, and the amygdala, which responds to emotionally arousing information, are bigger in men. A part of the hypothalamus, a brain region that regulates reproductive behavior, is also believed to be bigger in males.

At least one brain region has also been found to be different in male heterosexuals and homosexuals, also a part of the hypothalamus. And more recently, gay and straight men have been found to differ in how their brain responds to a scent in male sweat. 

But scientists don’t know whether homosexuality and transsexualism have anything in common biologically, beyond the fact that some people view both as aberrations—and that now, both are being found to have a possible genetic basis.

The idea that genes underlie transsexualism, at least among men who want to be women, has gained support from reports on twin and non-twin siblings who both have “this very rare condition, and from reports on families with more than one member” having it, Henningsson and colleagues wrote.

Gender identity is typically established by 18 to 24 months of age, when “boys come to know they are boys, and girls come to know they are girls,” according to the Merck Manual of Diagnosis and Therapy, 17th Edition.

Some people act in ways typically considered more appropriate for the other sex, but this doesn’t make them transsexuals, as long as they’re comfortable with their physical gender. Rather, transsexuals “believe that they are victims of a biologic accident,” the book says, “and that they are cruelly imprisoned within a body incompatible with their gender identity.”

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