SEX-RATIO IN NORMAL AND DISOMIC SPERM - EVIDENCE THAT THE EXTRA CHROMOSOME-21 PREFERENTIALLY SEGREGATES WITH THE Y-CHROMOSOME

In humans, deviations from a 1:1 male:female ratio have been identifie d in both chromosomally normal and trisomic live births: among normal newborns there is a slight excess of males, among trisomy 18 live born s a large excess of females, and among trisomy 21 live borns an excess of males. These differences could arise from differential production of or fertilization by Y- or X-bearing sperm or from selection against male or female conceptions. To examine the proportion of Y- and X-bea ring sperm in normal sperm and in sperm disomic for chromosomes 18 or 21, we used three-color FISH (to the X and Y and either chromosome 18 or chromosome 21) to analyze >300,000 sperm from 24 men. In apparently normal sperm, the sex ratio was nearly 1:1 (148,074 Y-bearing to 148, 657 X-bearing sperm), and the value was not affected by the age of the donor. Certain of the donors, however, had significant excesses of Y- or X-bearing sperm. In disomy 18 sperm, there were virtually identica l numbers of Y- and X-bearing sperm; thus, the excess of females in tr isomy 18 presumably is due to selection against male trisomic concepti ons. In contrast, we observed 69 Y-bearing and 44 X-bearing sperm diso mic for chromosome 21. This is consistent with previous molecular stud ies, which have identified an excess of males among paternally derived cases of trisomy 21, and suggests that some of the excess of males am ong Down syndrome individuals is attributable to a nondisjunctional me chanism in which the extra chromosome 21 preferentially segregates wit h the Y chromosome.