Extreme skewing of X chromosome inactivation in mothers of homosexual men

From the Journal of Human Genetics:

Extreme skewing of X chromosome inactivation in mothers of homosexual men
Sven Bocklandt * Steve Horvath * Eric Vilain
Abstract:
Human sexual preference is a sexually dimorphic
trait with a substantial genetic component. Linkage
of male sexual orientation to markers on the X chromosome
has been reported in some families. Here, we
measured X chromosome inactivation ratios in 97
mothers of homosexual men and 103 age-matched control
women without gay sons. The number of women
with extreme skewing of X-inactivation was significantly
higher in mothers of gay men (13/97=13%) compared
to controls (4/103=4%) and increased in mothers with
two or more gay sons (10/44=23%). Our findings support
a role for the X chromosome in regulating sexual
orientation in a subgroup of gay men.

Researchers in this study examined large numbers of cells from women who had at least two gay sons - 42 in total, appx 23% of participants.
As you probably remember from high school biology, in the case of the sex chromosomes, women carry two X chromosomes (XX) while men carry an X and a Y (XY). However, while women have two X chromosomes, only one is activated (in rare cases both are, and certain genetic disorders can result).
In most cases, X chromosome inactivation occurs at random: half of the cells in a woman's body will have one X chromosome inactivated, while the other half inactivate the other chromosome. They found something different in the case of these women: in nearly every cell that they examined the same X chromosome was inactivated.

Much of the previous scientific work has indicated that differing sexual orientation result from changes in multiple genes, rather than involving any one single "gay gene." These results suggest one possible mechanism that may be involved in the causation of homosexuality, whereby genetic shifts or alterations that would normally be "corrected" by introducing the normalizing factor of random activated X-chromosomal distribution would be negated by only one of the two X chromosomes being available for the use of genetic propogation.

The authors also state at the end of their discussion section:

"Recently, several identified autosomal loci suggested a multi-gene regulation of the sexual orientation pathway, as expected for a complex behavioral trait. We hypothesize that one central neuronal pathway establishes sexual attraction to either males or females, usually towards the opposite sex. However, a variety of genetic and non-genetic biological effects might intersect this pathway. Hence, there might be several subgroups of gay men and women, each with their own specific biological origin."

The implications of this are interesting, though not entirely novel. Essentially they purport that actual genetic or neurological causes for homosexuality may vary widely from one person to the next (where this skewing of chromosomal inactivation might only be one of many). This begs the question as to whether there are indeed varying "degrees" or even "classifications" of homosexuality, and whether these can be influenced entirely by differing genetic factors.


[Author'ss Note: I am of course leaving out of this discussion the possible involvement of environmental factors - the so-called nature vs nurture debate. That is not to say that I dismiss them in the slightest, only that they must be analyzed at a different level and with methods and tools beyond the general purview of a geneticist. They constitute an interesting and valid discussion in their own right]