Alleys Blind and Sighted

A common polymorphism of the SRD5A2 gene and transsexualism. Bentz EK, Schneeberger C, Hefler LA, van Trotsenburg M, Kaufmann U, Huber JC, Tempfer CB. Reprod Sci. 2007 Oct;14(7):705-9.

The relation between genetic variation of the androgen metabolism and transsexualism is unknown. In a case-control study of 100 male-to-female (MtF) transsexuals, 47 female-to-male (FtM) transsexuals, and 1670 controls, the authors assess allele and genotype frequencies of the steroid 5-alpha reductase (SRD5A2) Val89Leu polymorphism using polymerase chain reaction. Allele and genotype frequencies are not significantly different between MtF transsexuals and male controls
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Allele and genotype frequencies are also not significantly different between FtM transsexuals and female controls
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Of note, there is no gender-specific genotype distribution among controls. The SRD5A2 Val89Leu SNP is not associated with transsexualism, refuting SRD5A2 as a candidate gene of transsexualism.

As they say in the Classics, Bugger.

A polymorphism of the CYP17 gene related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism Bentz E, Hefler L, Kaufmann U, Huber J, Kolbus A, Tempfer C Fertility and Sterility , Volume 90 , Issue 1 , Pages 56 - 59

OBJECTIVE: To assess the association between transsexualism and allele and genotype frequencies of the common cytochrome P450 (CYP) 17 -34 T>C single nucleotide polymorphism (SNP). DESIGN: Case-control study. SETTING: Academic research institution. PATIENT(S): 102 male-to-female (MtF) and 49 female-to-male (FtM) transsexuals, 756 male controls, and 915 female controls.
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The MtF transsexuals had an allele distribution equivalent to male controls, whereas FtM transsexuals did not follow the gender-specific allele distribution of female controls but rather had an allele distribution equivalent to MtF transsexuals and male controls. CONCLUSION(S): These data support CYP17 as a candidate gene of FtM transsexualism and indicate that loss of a female-specific CYP17 T -34C allele distribution pattern is associated with FtM transsexualism.

See also New Scientist on the subject.

While there are many women with the variant who are not transsexual and many FtM transsexuals who lack it, the finding raises the possibility that the variant makes women more likely to feel that their bodies are of the wrong sex, and that this is a result of their brains having been exposed to higher than average levels of sex hormones during development.

"It may increase the likelihood that people will become transsexual," says Tempfer. But he stresses that their cultural environment is also important.

"The present study found that a mutant gene that ultimately results in higher testosterone levels is overrepresented in female-to male transsexualism, says Mikael Landén of the Karolinska Institute in Stockholm, Sweden.

"This is in line with what we previously know about masculinisation of the brain and is therefore less likely to be a chance finding", he says. "Hence, the study is important and adds to the notion that gender identity is influenced by sex hormones early in life, and that certain gene combinations make individuals more vulnerable to aberrant effects."

That would be in accordance with the known effects of DES - and Thalidomide. For Thalidomide to cause "aberrant effects", there must be a genetic pre-disposition, which is why only 1 in 10 were affected. We know that only 1 in 5 "aberrant effects" happen after DES exposure in the first trimester, strongly suggestive of a genetic predisposition being required too.

More pieces of the puzzle. And negative results, pruning the possibility-tree, are just as valuable as the occasional "find".

In summary, the model we now have is:

1. Hormones and/or gene sequences (not necessarily related to "sex chromosomes", but usually) cause a pre-natal pre-determined pre-disposition for later brain development.
2. This development leads to emotional and thinking patterns that usually (not always) result in solid gender identity formation, in accordance with Diamond's Biased-Interaction model.
3. Later still, both gross and fine structures of the brain differentiate to such an extent that they're detectable, caused by the same pre-natal factors.