Extreme skewing of X chromosome inactivation in mothers of homosexual men

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.

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References

  1. 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

    PubMed  CAS  Google Scholar 

  2. 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

    PubMed  Article  CAS  Google Scholar 

  3. 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

    PubMed  Article  CAS  Google Scholar 

  4. Blanchard R (2001) Fraternal birth order and the maternal immune hypothesis of male homosexuality. Horm Behav 40:105–114

    PubMed  Article  CAS  Google Scholar 

  5. Bocklandt S, Hamer DH (2003) Beyond hormones: a novel hypothesis for the biological basis of male sexual orientation. J Endocrinol Invest 26:8–12

    PubMed  CAS  Google Scholar 

  6. Brown CJ, Robinson WP (2000) The causes and consequences of random and non-random X chromosome inactivation in humans. Clin Genet 58:353–363

    PubMed  Article  CAS  Google Scholar 

  7. 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

    PubMed  Article  CAS  Google Scholar 

  8. 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

    PubMed  Article  CAS  Google Scholar 

  9. 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

    PubMed  Article  CAS  Google Scholar 

  10. Hamer D (1999) Genetics and male sexual orientation. Science 285:803

    Article  CAS  Google Scholar 

  11. 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

    PubMed  Article  CAS  Google Scholar 

  12. 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

    PubMed  Article  CAS  Google Scholar 

  13. 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

    PubMed  CAS  Google Scholar 

  14. 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

    PubMed  Article  CAS  Google Scholar 

  15. 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

    PubMed  Article  CAS  Google Scholar 

  16. 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

    PubMed  Article  CAS  Google Scholar 

  17. 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

    PubMed  Article  CAS  Google Scholar 

  18. 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

    PubMed  Article  Google Scholar 

  19. Turner WJ (1995) Homosexuality, type 1: an Xq28 phenomenon. Arch Sex Behav 24:109–134

    PubMed  Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank all the families whose participation in this study made our work possible.

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Correspondence to Sven Bocklandt.

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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

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Keywords

  • Androgen Receptor
  • Sexual Orientation
  • Sexual Attraction
  • Chromosome Inactivation
  • Androgen Receptor Gene