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.
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Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW (1992) Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am J Hum Genet 51:1229–1239
Bailey JM, Pillard RC, Dawood K, Miller MB, Farrer LA, Trivedi S, Murphy RL (1999) A family history study of male sexual orientation using three independent samples. Behav Genet 29:79–86
Biancalana V, Serville F, Pommier J, Julien J, Hanauer A, Mandel JL (1992) Moderate instability of the trinucleotide repeat in spino bulbar muscular atrophy. Hum Mol Genet 1:255–258
Blanchard R (2001) Fraternal birth order and the maternal immune hypothesis of male homosexuality. Horm Behav 40:105–114
Bocklandt S, Hamer DH (2003) Beyond hormones: a novel hypothesis for the biological basis of male sexual orientation. J Endocrinol Invest 26:8–12
Brown CJ, Robinson WP (2000) The causes and consequences of random and non-random X chromosome inactivation in humans. Clin Genet 58:353–363
Carrel L, Willard HF (1996) An assay for X inactivation based on differential methylation at the fragile X locus, FMR1. Am J Med Genet 64:27–30
Graves JA, Gecz J, Hameister H (2002) Evolution of the human X—a smart and sexy chromosome that controls speciation and development. Cytogenet Genome Res 99:141–145
Green R, Keverne E (2000) The disparate maternal aunt–uncle ratio in male transsexuals: an explanation invoking genomic imprinting. J Theor Biol 202:55–63
Hamer D (1999) Genetics and male sexual orientation. Science 285:803
Hamer D, Hu S, Magnuson V, Hu N, Pattatucci AM (1993) A linkage between DNA markers on the X chromosome and male sexual orientation. Science 261:321–327
Hu S, Pattatucci A, Patterson C, Li L, Fulker D, Cherny S, Kruglyak L, Hamer D (1995) Linkage between sexual orientation and chromosome Xq28 in males but not females. Nat Genet 11:248–256
Macke JP, Hu N, Hu S, Bailey M, King VL, Brown T, Hamer D, Nathans J (1993) Sequence variation in the androgen receptor gene is not a common determinant of male sexual orientation. Am J Hum Genet 53:844–852
Mustanski BS, Dupree MG, Nievergelt CM, Bocklandt S, Schork NJ, Hamer DH (2005) A genomewide scan of male sexual orientation. Hum Genet 116:272–278
Ozbalkan Z, Bagislar S, Kiraz S, Akyerli CB, Ozer HT, Yavuz S, Birlik AM, Calguneri M, Ozcelik T (2005) Skewed X chromosome inactivation in blood cells of women with scleroderma. Arthritis Rheum 52:1564–1570
Pegoraro E, Whitaker J, Mowery-Rushton P, Surti U, Lanasa M, Hoffman EP (1997) Familial skewed X inactivation: a molecular trait associated with high spontaneous-abortion rate maps to Xq28. Am J Hum Genet 61:160–170
Sabol SZ, Nelson ML, Fisher C, Gunzerath L, Brody CL, Hu S, Sirota LA, Marcus SE, Greenberg BD, Lucas FRt, Benjamin J, Murphy DL, Hamer DH (1999) A genetic association for cigarette smoking behavior. Health Psychol 18:7–13
Sandovici I, Naumova AK, Leppert M, Linares Y, Sapienza C (2004) A longitudinal study of X-inactivation ratio in human females. Hum Genet 115:387–392
Turner WJ (1995) Homosexuality, type 1: an Xq28 phenomenon. Arch Sex Behav 24:109–134
We would like to thank all the families whose participation in this study made our work possible.
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Bocklandt, S., Horvath, S., Vilain, E. et al. Extreme skewing of X chromosome inactivation in mothers of homosexual men. Hum Genet 118, 691–694 (2006). https://doi.org/10.1007/s00439-005-0119-4
- Androgen Receptor
- Sexual Orientation
- Sexual Attraction
- Chromosome Inactivation
- Androgen Receptor Gene