Investigation of factors associated with paternal nondisjunction of chromosome 21.
Previous studies on relatively small samples of individuals with trisomy 21 caused by paternally derived errors have shown that: (1) advanced paternal age is not a risk factor for chromosome 21 nondisjunction (NDJ), (2) absence of recombination, but not the location of recombination is associated with paternal NDJ and (3) there is an excess of males among live-births with paternally derived trisomy 21. An excess of males is also observed among all individuals with trisomy 21. Using 128 families that had a child with trisomy 21 due to a paternally derived error, we examined: paternal age, recombination and the male/female sex ratio. We genotyped STRs along 21q to identify the origin of the error and the location of recombination on the paternal chromosome. Results showed that 32% of paternal meiotic errors occurred in meiosis I (MI) and 68% in meiosis II (MII). We confirmed the lack of a paternal age association with either type of error (mean paternal age for controls, MI, and MII errors: 31.3 +/- 6.6, 32.2 +/- 6.3, 30.6 +/- 6.5, respectively). However, contrary to previous findings, we did not find altered patterns of recombination among paternal MI or MII errors. We found an increased male/female sex ratio among paternal (1.28, 95% CI: 0.68-1.91) and maternal (1.16, 95% CI: 1.02-1.33) meiotic errors. While the sex ratio among individuals with paternal errors was not statistically significant, these findings suggest that selection against female fetuses with trisomy 21 may contribute to the excess of males observed among all individuals with trisomy 21.
Oliver
Tiffany Renee
TR
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA. toliver@genetics.emory.edu
Bhise
Archit
A
Feingold
Eleanor
E
Tinker
Stuart
S
Masse
Nirupama
N
Sherman
Stephanie L
SL
D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D016001:Confidence Intervals; D004314:Down Syndrome / Q000235:genetics; D005220:Fathers; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008540:Meiosis; D018895:Microsatellite Repeats / Q000235:genetics; D009630:Nondisjunction, Genetic; D010331:Paternal Age; D012307:Risk Factors; D012744:Sex Ratio; D012854:Sister Chromatid Exchange / Q000235:genetics