The disparate maternal aunt-uncle ratio in male transsexuals: an explanation invoking genomic imprinting

A significant skewing in the sex ratio in favour of females has been report ed for the families of homosexual men such that there are fewer maternal un cles than aunts. This finding is repeated for a large series of transsexual families in this study. Four hundred and seventeen male-to-female transsex uals and 96 female-to-male transsexuals were assessed. Male-to-female trans sexuals have a significant excess of maternal aunts vs, uncles. No differen ces from the expected parity were found for female-to-male transsexuals or on the paternal side. A posited explanation for these findings invokes X in activation and genes on the X chromosome that escape inactivation but may b e imprinted. Our hypothesis incorporates the known familial traits in the f amilies of homosexuals and transsexuals by way of retention of the grand pa rental epigenotype on the X chromosome. Generation one would be characteriz ed by a failure to erase the paternal imprints on the paternal X chromosome . Daughters of this second generation would produce sons that are XpY and X mY. Since XpY expresses Xist, the X chromosome is silenced and half of the sons are lost at the earliest stages of pregnancy because of the normal req uirement for paternal X expression in extra-embryonic tissues. Females surv ive by virtue of inheriting two X chromosomes, and therefore the possibilit y of X chromosome counting and choice during embryonic development. In gene ration three, sons inheriting the paternal X after its second passage throu gh the female germline survive, but half would inherit the feminizing Xp im printed genes. These genes could pre-dispose the sons to feminization and s ubsequent development of either homosexuality or transsexualism (C) 2000 Ac ademic Press.