Investigation of Factors Associated With Paternal Nondisjunction of Chromosome 21

• Type of Material: Article
• Authors: Tiffany R. Oliver, Emory University; Archit Bhise, Emory University; Eleanor Feingold, University of Pittsburgh; Stuart Tinker, Emory University; Nirupama Masse, Emory University; Stephanie Sherman, Emory University
• Language: English
• Date: 2009-08-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Wiley-Liss, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/ajmg.a.32942
• Title of Journal or Parent Work: American Journal of Medical Genetics Part A
• ISSN: 1552-4825
• Volume: 149A
• Issue: 8
• Start Page: 1685
• End Page: 1690
• Keywords: MEIOTIC STAGE; Life Sciences & Biomedicine; meiosis; RECOMBINATION; ORIGIN; spermatogenesis; DNA POLYMORPHISMS; EXCESS; RISK; Genetics & Heredity; TRISOMY-21; Down syndrome; sex ratio; altered recombination; Science & Technology; HUMANS; CONFIGURATIONS; paternal nondisjunction; ANEUPLOIDY
• Research Categories: Biology, Biostatistics; Biology, Genetics

Abstract

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 observedamong all individuals with trisomy 21.