Evidence for nonhomologous meiotic coorientation in man

Nonhomologous meiotic co-orientation (NMC) was postulated for humans a half of century ago to explain the association between the presence of a rearranged chromosome(s) and the occurrence of aneuploidy for an unrelated chromosome ("interchromosomal effect", ICE). However subsequent studies did not support meiotic nature of ICE phenomenon. At the same time, NMC model can be fruitful for solving a number of problems regarding the etiology of human aneuploidy. Published and own data on the offspring of 322 parental carrier of chromosomal abnormality were analyzed according to the carrier's gender. In families with transmission of der(21;21), among patients with maternally derived trisomy 21 (T21), there is a typical male-biased sex ratio (SR), with 33 males/28 females. Among patients with paternally derived T21, five-fold male prevalence is observed (16 males/3 females), p = 0.0373. In families with maternal balanced non-contributing rearrangement (Rea), SR was male-biased among T21 patients, both those inherited (42 males/30 females) and not inherited the Rea (17 males/11 females). However, in families with paternal balanced Rea, there is an impressive difference between T21 offspring with transmitted paternal Rea and those not inherited paternal Rea, 49 males/21 females vs 4 males/15 females, p = 0.0003. A female predominance is also observed among non-trisomic offspring of paternal carriers of gonadal mosaicism for T21 (2 males/12 females), but not in non-trisomic offspring of maternal carriers (19 males/16 females), p = 0.0253. Unusual sex ratios in offspring of male carriers are considered as the result of NMC of a chromosome abnormality with the X chromosome operating in spermatogenesis.