Original Investigation

Human Genetics

, Volume 131, Issue 7, pp 1039-1046

First online:

Altered patterns of multiple recombinant events are associated with nondisjunction of chromosome 21

  • Tiffany Renee OliverAffiliated withDepartment of Human Genetics, Emory University School of MedicineDepartment of Biology, Spelman College Email author 
  • , Stuart W. TinkerAffiliated withDepartment of Human Genetics, Emory University School of Medicine
  • , Emily Graves AllenAffiliated withDepartment of Human Genetics, Emory University School of Medicine
  • , Natasha HollisAffiliated withDepartment of Human Genetics, Emory University School of Medicine
  • , Adam E. LockeAffiliated withDepartment of Human Genetics, Emory University School of Medicine
  • , Lora J. H. BeanAffiliated withDepartment of Human Genetics, Emory University School of Medicine
  • , Reshmi ChowdhuryAffiliated withDepartment of Pediatrics, University of Pennsylvania
  • , Ferdouse BegumAffiliated withDepartment of Human Genetics, Graduate School of Public Health, University of PittsburghDepartment of Biostatistics, Graduate School of Public Health, University of Pittsburgh
  • , Mary MarazitaAffiliated withDepartment of Human Genetics, Graduate School of Public Health, University of PittsburghDivision of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh
    • , Vivian CheungAffiliated withDepartments of Pediatrics and Genetics, University of PennsylvaniaHoward Hughes Medical Institute, University of PennsylvaniaDepartment of Genetics, University of Pennsylvania
    • , Eleanor FeingoldAffiliated withDepartment of Human Genetics, Graduate School of Public Health, University of PittsburghDepartment of Biostatistics, Graduate School of Public Health, University of Pittsburgh
    • , Stephanie L. ShermanAffiliated withDepartment of Human Genetics, Emory University School of Medicine

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

We have previously examined characteristics of maternal chromosomes 21 that exhibited a single recombination on 21q and proposed that certain recombination configurations are risk factors for either meiosis I (MI) or meiosis II (MII) nondisjunction. The primary goal of this analysis was to examine characteristics of maternal chromosomes 21 that exhibited multiple recombinant events on 21q to determine whether additional risk factors or mechanisms are suggested. In order to identify the origin (maternal or paternal) and stage (MI or MII) of the meiotic errors, as well as placement of recombination, we genotyped over 1,500 SNPs on 21q. Our analyses included 785 maternal MI errors, 87 of which exhibited two recombinations on 21q, and 283 maternal MII errors, 81 of which exhibited two recombinations on 21q. Among MI cases, the average location of the distal recombination was proximal to that of normally segregating chromosomes 21 (35.28 vs. 38.86 Mb), a different pattern than that seen for single events and one that suggests an association with genomic features. For MII errors, the most proximal recombination was closer to the centromere than that on normally segregating chromosomes 21 and this proximity was associated with increasing maternal age. This pattern is same as that seen among MII errors that exhibit only one recombination. These findings are important as they help us better understand mechanisms that may underlie both age-related and nonage-related meiotic chromosome mal-segregation.