Allele-specific DNA methylation (ASM) is a hallmark of imprinted genes, but ASM in the larger nonimprinted fraction of the genome is less well characterized. Using methylation-sensitive SNP analysis (MSNP), we surveyed the human genome at 50K and 250K resolution, identifying ASM as recurrent genotype call conversions from heterozygosity to homozygosity when genomic DNAs were predigested with the methylation-sensitive restriction enzyme HpaII. Using independent assays, we confirmed ASM at 16 SNP-tagged loci distributed across various chromosomes. At 12 of these loci (75%), the ASM tracked strongly with the sequence of adjacent SNPs. Further analysis showed allele-specific mRNA expression at two loci from this methylation-based screen--the vanin and CYP2A6-CYP2A7 gene clusters--both implicated in traits of medical importance. This recurrent phenomenon of sequence-dependent ASM has practical implications for mapping and interpreting associations of noncoding SNPs and haplotypes with human phenotypes.
The central dogma of mammalian brain sexual differentiation has contended that sex steroids of gonadal origin organize the neural circuits of the developing brain. Recent evidence has begun to challenge this idea and has suggested that, independent of the masculinizing effects of gonadal secretions, XY and XX brain cells have different patterns of gene expression that influence their differentiation and function. We have previously shown that specific differences in gene expression exist between male and female developing brains and that these differences precede the influences of gonadal hormones. Here we demonstrate that the Y chromosome-linked, male-determining gene Sry is specifically expressed in the substantia nigra of the adult male rodent in tyrosine hydroxylase-expressing neurons. Furthermore, using antisense oligodeoxynucleotides, we show that Sry downregulation in the substantia nigra causes a statistically significant decrease in tyrosine hydroxylase expression with no overall effect on neuronal numbers and that this decrease leads to motor deficits in male rats. Our studies suggest that Sry directly affects the biochemical properties of the dopaminergic neurons of the nigrostriatal system and the specific motor behaviors they control. These results demonstrate a direct male-specific effect on the brain by a gene encoded only in the male genome, without any mediation by gonadal hormones.
Biological differences between men and women contribute to many sex-specific illnesses and disorders. Historically, it was argued that such differences were largely, if not exclusively, due to gonadal hormone secretions. However, emerging research has shown that some differences are mediated by mechanisms other than the action of these hormone secretions and in particular by products of genes located on the X and Y chromosomes, which we refer to as direct genetic effects. This paper reviews the evidence for direct genetic effects in behavioral and brain sex differences. We highlight the `four core genotypes' model and sex differences in the midbrain dopaminergic system, specifically focusing on the role of Sry. We also discuss novel research being done on unique populations including people attracted to the same sex and people with a cross-gender identity. As science continues to advance our understanding of biological sex differences, a new field is emerging that is aimed at better addressing the needs of both sexes: gender-based biology and medicine. Ultimately, the study of the biological basis for sex differences will improve healthcare for both men and women.
Gender identity-one's sense of being a man or a woman-is a fundamental perception experienced by all individuals that extends beyond biological sex. Yet, what contributes to our sense of gender remains uncertain. Since individuals who identify as transsexual report strong feelings of being the opposite sex and a belief that their sexual characteristics do not reflect their true gender, they constitute an invaluable model to understand the biological underpinnings of gender identity. We analyzed MRI data of 24 male-to-female (MTF) transsexuals not yet treated with cross-sex hormones in order to determine whether gray matter volumes in MTF transsexuals more closely resemble people who share their biological sex (30 control men), or people who share their gender identity (30 control women). Results revealed that regional gray matter variation in MTF transsexuals is more similar to the pattern found in men than in women. However, MTF transsexuals show a significantly larger volume of regional gray matter in the right putamen compared to men. These findings provide new evidence that transsexualism is associated with distinct cerebral pattern, which supports the assumption that brain anatomy plays a role in gender identity.
This exploratory study used consensual qualitative research methodology (Hill et al., 2005) to analyze what gay men associate with masculinity and femininity, how they feel masculine ideals affect their self-image, and how masculine ideals affect their same-sex relationships. Written responses were collected from 547 self-identified gay men in the U.S. via an Internet-based survey. Findings supported previous reports that perceptions of gender roles among gay men appear based on masculine and feminine stereotypes. Additionally, more adverse versus positive effects on self-image and same-sex romantic relationships were reported including difficulty being emotional and affectionate, pressure to be physically attractive, and pressure to appear masculine in order to be accepted by society and to be seen as desirable by other gay men. While research on gay men's experience with masculinity continues, psychologists should consider the possible influence of traditional masculine ideals when conceptualizing their gay male clients. KeywordsGay Men (Homosexuality); Masculinity; Gender Roles; Femininity; Straight-acting Reported Effects of Masculine Ideals on Gay MenSocietal conceptions of masculinity affect the self-image and relationships of many gay men in the United States (U.S.). The topic of how and why gay men are affected by this repeatedly appears within the popular gay press (e.g., Alvear, 2004;Cummings, 1999;Rice, 2006) and sparks controversy within the gay community. For instance, Bergling (2001) Correspondence concerning this article should be addressed to Francisco J. Sánchez, UCLA School of Medicine, 695 Charles Young Dr. S #5524, Los Angeles, CA 90025-7088. Electronic mail may be sent to fjsanchez@mednet.ucla.edu. Publisher's Disclaimer: The following manuscript is the final accepted manuscript. It has not been subjected to the final copyediting, fact-checking, and proofreading required for formal publication. It is not the definitive, publisher-authenticated version. The American Psychological Association and its Council of Editors disclaim any responsibility or liabilities for errors or omissions of this manuscript version, any version derived from this manuscript by NIH, or other third parties. The published version is available at www.apa.org/pubs/journals/men. NIH Public Access Author ManuscriptPsychol Men Masc. Author manuscript; available in PMC 2010 July 12. These real-life examples and the suggestion that masculine ideals significantly affect many gay men may surprise people who are not intimately familiar with the gay community-a community that is often perceived as accepting of individual differences. Yet, the reality is that traditional masculine ideals affect how gay men feel about themselves (Szymanski & Carr, 2008) and their same-sex relationships (Wester, Pionke, & Vogel, 2005). While many gay men struggle with these issues, scientific research on the effect of masculine ideals on gay men is lacking. Although many scholars have written about the topic (e.g., Humphries, 1985;Kleinberg...
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