Extreme skewing of X chromosome inactivation in mothers of homosexual men

Bocklandt, Sven; Steve, Horvath; Vilain, Éric; Hamer, Dean H.

doi:10.1007/s00439-005-0119-4

Cited by 67 publications

(32 citation statements)

References 17 publications

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“…The first studies using this method reported nonsignificant results (Ramagopalan et al 2010;Drabant et al 2012) with just a relevant, albeit not significant, effect, possibly a result of a low power of the tests, in region q12.3 of chromosome 8, associated with male HS subjects (Drabant et al 2012). However, Sanders et al (2012), in a more recent large and systematic multicenter study (see also Bailey 2014), found a significant association with the region Xq28 and a region in chromosome 8, substantially confirming the earliest findings of Hamer et al (1993) and the findings, with the earlier methods, by Mustanski et al (2005) and Bocklandt et al (2006).…”

Section: Criticisms To Genetic Model Influencing Hssupporting

confidence: 59%

“…These investigators looked at the entire human genome of males who had two or more HS brothers, and found linkage with polymorphisms on three chromosomes-7, 8, and 10-that were shared by approximately 60% of the HS brothers in the study. Later studies also showed extremely skewed X inactivation in mothers of male HS as compared with mothers of heterosexuals, further suggesting an involvement of the X chromosome (Bocklandt et al 2006), as well as other maternally imprinted polymorphisms on the autosomes (Bocklandt and Hamer 2003). More recently, a new method supplemented linkage analysis by investigating higher resolution genome-wide association of single nucleotide polymorphism with phenotypic traits.…”

Section: Criticisms To Genetic Model Influencing Hsmentioning

confidence: 99%

“…An interesting instance of this effect would be a possible genetic substrate for the induced immunization hypothesized to be at the basis of the FBO effect in the section Fraternal Birth Order Effect (Blanchard and Bogaert, 1996;Blanchard 2001Blanchard , 2004Cantor et al 2002;Bogaert and Skorska, 2011). The analysis in CCZ also included (2) a selection model describing a form of maternal genomic imprinting (Bocklandt and Hamer 2003;Mustanski et al 2005;Bocklandt et al 2006), according to which the fitness depends on alleles that are active in a son only if inherited from the mother. This is described by distinguishing two male genotypes depending on the provenience of the gametes.…”

Section: Genetic Models For Male Hsmentioning

confidence: 99%

See 2 more Smart Citations

Human Homosexuality: A Paradigmatic Arena for Sexually Antagonistic Selection?

Ciani

Battaglia

Zanzotto

2015

Cold Spring Harb Perspect Biol

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Sexual conflict likely plays a crucial role in the origin and maintenance of homosexuality in our species. Although environmental factors are known to affect human homosexual (HS) preference, sibling concordances and population patterns related to HS indicate that genetic components are also influencing this trait in humans. We argue that multilocus, partially Xlinked genetic factors undergoing sexually antagonistic selection that promote maternal female fecundity at the cost of occasional male offspring homosexuality are the best candidates capable of explaining the frequency, familial clustering, and pedigree asymmetries observed in HS male proband families. This establishes male HS as a paradigmatic example of sexual conflict in human biology. HS in females, on the other hand, is currently a more elusive phenomenon from both the empirical and theoretical standpoints because of its fluidity and marked environmental influence. Genetic and epigenetic mechanisms, the latter involving sexually antagonistic components, have been hypothesized for the propagation and maintenance of female HS in the population. However, further data are needed to truly clarify the evolutionary dynamics of this trait. Sexual conflict, the general theme of this collection, has emerged in the last decades as a main research topic in evolutionary biology. Its possible ubiquity and key role have become clear in many phenomena, from speciation to genetic diversity maintenance in populations, sexual phenotypic dimorphism, asymmetric mating and parenting strategies, antagonistic coevolution, and others (Bonduriansky and Chenoweth 2009;Rice et al. 2013; see also Gavrilets 2014). A most interesting example of sexual conflict is given by homosexual (HS) behavior and mate preference in humans, a topic whose societal impact is widely felt at present.Homosexuality is not confined just to our species, but is also occasionally present in numerous animals (Bagemihl 1999;Sommer and Vasey 2006), with permanent, long-term samesex pair bonding having been reported in some birds and ungulates (Bagemihl 1999;Ngun et al. 2011). The presence of not solely sporadic and opportunistic HS behavior has also been observed in nonhuman primates, which suggests our hominid ancestry might also have had HS individuals (Vasey 1995).The main evolutionary questions about HS in our species do not concern occasional HS behavior, which might have, in various con-

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Section: Criticisms To Genetic Model Influencing Hssupporting

confidence: 59%

Section: Criticisms To Genetic Model Influencing Hsmentioning

confidence: 99%

Section: Genetic Models For Male Hsmentioning

confidence: 99%

See 1 more Smart Citation

Human Homosexuality: A Paradigmatic Arena for Sexually Antagonistic Selection?

Ciani

Battaglia

Zanzotto

2015

Cold Spring Harb Perspect Biol

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“…A different technique also indicated a role for the X-chromosome in male sexual orientation. Women with gay sons appeared to have an extreme skewing of X-inactivation as compared to mothers without gay sons (107). Although this unusual methylation pattern supports a possible role of the X-chromosome in male homosexuality, its mechanism of action is far from clear.…”

mentioning

confidence: 87%

Sexual differentiation of the human brain in relation to gender identity and sexual orientation

Savić

Garcı́a-Falgueras

Swaab

2010

Progress in Brain Research

125

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SummaryDuring the intrauterine period the fetal brain develops in the male direction through a direct action of testosterone on the developing nerve cells, or in the female direction through the absence of this hormone surge. In this way, our gender identity (the conviction of belonging to the male or female gender) and sexual orientation are programmed into our brain structures when we are still in the womb. However, since sexual differentiation of the genitals takes place in the first two months of pregnancy and sexual differentiation of the brain starts in the second half of pregnancy, these two processes can be influenced independently, which may result in transsexuality. This also means that in the event of ambiguous sex at birth, the degree of masculinization of the genitals may not reflect the degree of masculinization of the brain. There is no proof that social environment after birth has an effect on gender identity or sexual orientation.KEY WORDS: gender identity, homosexuality, human brain, sexual orientation, sexual differentiation, transsexuality. Sexual organization and activation of the human brainThe process of sexual differentiation of the brain brings about permanent changes in brain structures and functions via interactions of the developing neurons with the environment, understood in its widest sense. The environment of a developing neuron is formed by the surrounding nerve cells and the child's circulating hormones, as well as the hormones, nutrients, medication and other chemical substances from the mother and the environment that enter the fetal circulation via the placenta. All these factors may have a lasting effect on the sexual differentiation of the brain. The testicles and ovaries develop in the sixth week of pregnancy. This occurs under the influence of a cascade of genes, starting with the sex-determining gene on the Y chromosome (SRY). The production of testosterone by a boy's testes is necessary for sexual differentiation of the sexual organs between weeks 6 and 12 of pregnancy. The peripheral conversion of testosterone into dihydrotestosterone is essential for the formation of a boy's penis, prostate and scrotum. Instead, the development of the female sexual organs in the womb is based primarily on the absence of androgens (1). Once the differentiation of the sexual organs into male or female is settled, the next thing that is differentiated is the brain, under the influence, mainly, of sex hormones on the developing brain cells. The changes (permanent) brought about in this stage have organizing effects; later, during puberty, the brain circuits that developed in the womb are activated by sex hormones. This paradigm of sexual differentiation of the brain has been well established, ever since the first paper by Phoenix et al. (2). The fetal brain is protected against the effect of circulating estrogens from the mother by the protein α-fetoprotein, which is produced by the fetus and binds strongly to estrogens but not to testosterone (3,4). However, estrogens do not only reach th...

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“…High frequency of skewed XCI has also been observed in recurrent spontaneous abortions (Lanasa et al 1999;Sangha et al 1999), X-linked mental retardation (Plenge et al 2002), breast and ovarian cancers (Kristiansen et al 2002), and in mothers of homosexual men (Bocklandt et al 2006). In addition, it has been hypothesized that skewed XCI could be a factor that inXuences female predisposition to autoimmunity: recently skewed XCI has been reported in three autoimmune disorders, scleroderma (Ozbalkan et al 2005), autoimmune thyroid diseases (Brix et al 2005;Ozcelik et al 2006), and premature ovarian failure (Sato et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Extremely skewed X-chromosome inactivation is increased in pre-eclampsia

Dölen

et al. 2006

Hum Genet

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Pre-eclampsia is a disorder that aVects approximately 5% of pregnancies. We tested the hypothesis that skewed X-chromosome inactivation (XCI) could be involved in the pathogenesis of preeclampsia. Peripheral blood DNA was obtained from 67 pre-eclampsia patients and 130 control women. Androgen receptor (AR) was analyzed by the HpaII/ polymerase chain reaction assay to assess XCI patterns in DNA extracted from peripheral-blood cells. In addition, buccal cells were obtained from seven patients, and the analysis repeated. Extremely skewed XCI was observed in 10 of 46 informative patients (21.74%), and in 2 of 86 informative controls (2.33%, P = 0.0005; 2 test). Our Wndings support a role for the X-chromosome in the pathogenesis of pre-eclampsia in a subgroup of patients.

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Extreme skewing of X chromosome inactivation in mothers of homosexual men

Cited by 67 publications

References 17 publications

Human Homosexuality: A Paradigmatic Arena for Sexually Antagonistic Selection?

Human Homosexuality: A Paradigmatic Arena for Sexually Antagonistic Selection?

Sexual differentiation of the human brain in relation to gender identity and sexual orientation

Extremely skewed X-chromosome inactivation is increased in pre-eclampsia

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