Effect of paracentric inversion on Meiosis and reproduction

Abstract

Paracentric inversions are intrachromosomal rearrangements that involve inversion of a segment on one arm of a chromosome. Unlike other rearrangements, the frequency of paracentric inversions and that of their recombinants is low in the normal human population as well as in clinically defined ones. The effect of heterozygosity for each of a variety of paracentric inversions (varying in the length of the inverted segment and location relative to the centromere), on some aspects of meiosis and reproduction, in male and female mice, were investigated to determine the existence of mechanisms which may explain this observation. -- In male mice, heterozygosity for paracentric inversions involving large segments, was associated with meiotic disturbance, measured by a decrease in the proportion of haploid secondary spermatocytes and an increase in that of heteroploid secondary spermatocytes. This disturbance appears to be associated with dicentric recombinants. Studies suggest that loop formation during the pachytene stage of spermatogenesis has a role in preventing crossover and consequently recombinant formation. Association between size of the inverted segment and meiotic disturbance was not evident in female heterozygotes. -- Despite meiotic disturbance in male heterozygotes, litter size, a measure of postnatal phenotypic expression of chromosomal rearrangement, is not affected, suggesting pre-gametic selection. Pre-gametic selection and consequent reduction or absence of phenotypic expression in male heterozygotes may result in underascertainment of paracentric inversion. On the contrary, despite lack of significant meiotic disturbance, reduction in litter size is observed in females heterozygous for some inversions. These observations in females suggest post-gametic and possibly post fertilization selection. Differences between males and females in the stage at which selection operates may account for differences in the efficiency of selection in the two sexes. This may explain why the mother, rather than the father, is the carrier of paracentric inversion in most instances of recombinants reported in humans. -- The observations made in this study, suggest that a variety of unique factors may be responsible for the low frequency of balanced paracentric inversions and their recombinants in humans. They are: cytogenetic limitations in the identification of the inversion, meiotic mechanisms that suppress recombinant formation, efficient pre-gametic selection in male heterozygotes and failure of the resulting gametic loss to affect reproductive fitness in male heterozygotes.