The meiotic segregation of human sperm chromosomes in two men with accessory marker chromosomes

Accessory marker chromosomes are occasionally discovered in normal individuals and they are presumed 'clinically inert' since they do not appear to have any phenotypic effect. However, they do pose a theoretical risk at meiosis since they could disrupt the normal pairing and disjunction of homologous chromosomes. Sperm chromosome complements have been studied in two normal males, each of whom carry a small bisatellited accessory marker chromosome 47,XY,+mar (psps), to determine if these marker chromosomes are associated with an increased frequency of aneuploid gametes. Pronuclear chromosomes were visualized after in vitro fertilization of golden hamster eggs with human sperm. The frequency of sperm complements containing a marker chromosome was not significantly different from 50% as theoretically expected, in either male (17/43 and 13/31 with marker chromosomes). One male had 2/43 (4.7%) aneuploid sperm, which is very close to the average frequency of aneuploid sperm seen in control donors (5%). The other male had 6/31 complements with chromosomal abnormalities. One set of sperm chromosomes had structural abnormalities, and five (16.1%) had numerical abnormalities. This frequency of aneuploidy is significantly elevated over the frequency seen in control donors (P = .0002). It is particularly interesting that all the abnormalities involved small chromosomes, as would be expected if the marker chromosome participated in distributive pairing and thereby disrupted normal disjunction of chromosomes of similar size. These preliminary results suggest that accessory marker chromosomes may increase the risk of aneuploid gametes in some individuals.