Skip to main content
Genetics logoLink to Genetics
. 2002 Jul;161(3):1219–1224. doi: 10.1093/genetics/161.3.1219

Molecular analysis of nondisjunction in mice heterozygous for a Robertsonian translocation.

Lara A Underkoffler 1, Laura E Mitchell 1, A Russell Localio 1, Shannon M Marchegiani 1, Justin Morabito 1, Joelle N Collins 1, Rebecca J Oakey 1
PMCID: PMC1462172  PMID: 12136024

Abstract

A Robertsonian translocation results in a metacentric chromosome produced by the fusion of two acrocentric chromosomes. Rb heterozygous mice frequently generate aneuploid gametes and embryos, providing a good model for studying meiotic nondisjunction. We intercrossed mice heterozygous for a (7.18) Robertsonian translocation and performed molecular genotyping of 1812 embryos from 364 litters with known parental origin, strain, and age. Nondisjunction events were scored and factors influencing the frequency of nondisjunction involving chromosomes 7 and 18 were examined. We concluded the following: 1. The frequency of nondisjunction among 1784 embryos (3568 meioses) was 15.9%. 2. Nondisjunction events were distributed nonrandomly among progeny. This was inferred from the distribution of the frequency of trisomics and uniparental disomics (UPDs) among all litters. 3. There was no evidence to show an effect of maternal or paternal age on the frequency of nondisjunction. 4. Strain background did not play an appreciable role in nondisjunction frequency. 5. The frequency of nondisjunction for chromosome 18 was significantly higher than that for chromosome 7 in males. 6. The frequency of nondisjunction for chromosome 7 was significantly higher in females than in males. These results show that molecular genotyping provides a valuable tool for understanding factors influencing meiotic nondisjunction in mammals.

Full Text

The Full Text of this article is available as a PDF (69.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson L. K., Reeves A., Webb L. M., Ashley T. Distribution of crossing over on mouse synaptonemal complexes using immunofluorescent localization of MLH1 protein. Genetics. 1999 Apr;151(4):1569–1579. doi: 10.1093/genetics/151.4.1569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker S. M., Plug A. W., Prolla T. A., Bronner C. E., Harris A. C., Yao X., Christie D. M., Monell C., Arnheim N., Bradley A. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet. 1996 Jul;13(3):336–342. doi: 10.1038/ng0796-336. [DOI] [PubMed] [Google Scholar]
  3. Beck J. A., Lloyd S., Hafezparast M., Lennon-Pierce M., Eppig J. T., Festing M. F., Fisher E. M. Genealogies of mouse inbred strains. Nat Genet. 2000 Jan;24(1):23–25. doi: 10.1038/71641. [DOI] [PubMed] [Google Scholar]
  4. Broman K. W., Murray J. C., Sheffield V. C., White R. L., Weber J. L. Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genet. 1998 Sep;63(3):861–869. doi: 10.1086/302011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Catala V., Estop A. M., Santalo J., Egozcue J. Sexual immaturity and maternal age: incidence of aneuploidy and polyploidy in first-cleavage mouse embryos. Cytogenet Cell Genet. 1988;48(4):233–237. doi: 10.1159/000132635. [DOI] [PubMed] [Google Scholar]
  6. Davisson M. T., Akeson E. C. Recombination suppression by heterozygous Robertsonian chromosomes in the mouse. Genetics. 1993 Mar;133(3):649–667. doi: 10.1093/genetics/133.3.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dobson M. J., Pearlman R. E., Karaiskakis A., Spyropoulos B., Moens P. B. Synaptonemal complex proteins: occurrence, epitope mapping and chromosome disjunction. J Cell Sci. 1994 Oct;107(Pt 10):2749–2760. doi: 10.1242/jcs.107.10.2749. [DOI] [PubMed] [Google Scholar]
  8. Fabricant J. D., Schneider E. L. Studies of the genetic and immunologic components of the maternal age effect. Dev Biol. 1978 Oct;66(2):337–343. doi: 10.1016/0012-1606(78)90242-7. [DOI] [PubMed] [Google Scholar]
  9. Garagna S., Marziliano N., Zuccotti M., Searle J. B., Capanna E., Redi C. A. Pericentromeric organization at the fusion point of mouse Robertsonian translocation chromosomes. Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):171–175. doi: 10.1073/pnas.98.1.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hamerton J. L., Canning N., Ray M., Smith S. A cytogenetic survey of 14,069 newborn infants. I. Incidence of chromosome abnormalities. Clin Genet. 1975 Oct;8(4):223–243. doi: 10.1111/j.1399-0004.1975.tb01498.x. [DOI] [PubMed] [Google Scholar]
  11. Hassold T. J. The origin of aneuploidy in humans. Basic Life Sci. 1985;36:103–115. doi: 10.1007/978-1-4613-2127-9_7. [DOI] [PubMed] [Google Scholar]
  12. Hassold T., Merrill M., Adkins K., Freeman S., Sherman S. Recombination and maternal age-dependent nondisjunction: molecular studies of trisomy 16. Am J Hum Genet. 1995 Oct;57(4):867–874. [PMC free article] [PubMed] [Google Scholar]
  13. Hodges C. A., LeMaire-Adkins R., Hunt P. A. Coordinating the segregation of sister chromatids during the first meiotic division: evidence for sexual dimorphism. J Cell Sci. 2001 Jul;114(Pt 13):2417–2426. doi: 10.1242/jcs.114.13.2417. [DOI] [PubMed] [Google Scholar]
  14. Moens P. B., Pearlman R. E., Heng H. H., Traut W. Chromosome cores and chromatin at meiotic prophase. Curr Top Dev Biol. 1998;37:241–262. doi: 10.1016/s0070-2153(08)60176-3. [DOI] [PubMed] [Google Scholar]
  15. Nicolaidis P., Petersen M. B. Origin and mechanisms of non-disjunction in human autosomal trisomies. Hum Reprod. 1998 Feb;13(2):313–319. doi: 10.1093/humrep/13.2.313. [DOI] [PubMed] [Google Scholar]
  16. Sherman S. L., Petersen M. B., Freeman S. B., Hersey J., Pettay D., Taft L., Frantzen M., Mikkelsen M., Hassold T. J. Non-disjunction of chromosome 21 in maternal meiosis I: evidence for a maternal age-dependent mechanism involving reduced recombination. Hum Mol Genet. 1994 Sep;3(9):1529–1535. doi: 10.1093/hmg/3.9.1529. [DOI] [PubMed] [Google Scholar]
  17. Vekemans M. An investigation of factors influencing the survival of trisomic fetuses in the mouse. Prog Clin Biol Res. 1989;311:245–262. [PubMed] [Google Scholar]
  18. Wallace B. M., Searle J. B., Everett C. A. Male meiosis and gametogenesis in wild house mice (Mus musculus domesticus) from a chromosomal hybrid zone; a comparison between "simple" Robertsonian heterozygotes and homozygotes. Cytogenet Cell Genet. 1992;61(3):211–220. doi: 10.1159/000133410. [DOI] [PubMed] [Google Scholar]
  19. Warburton D., Kinney A. Chromosomal differences in susceptibility to meiotic aneuploidy. Environ Mol Mutagen. 1996;28(3):237–247. doi: 10.1002/(SICI)1098-2280(1996)28:3<237::AID-EM7>3.0.CO;2-A. [DOI] [PubMed] [Google Scholar]
  20. Woods L. M., Hodges C. A., Baart E., Baker S. M., Liskay M., Hunt P. A. Chromosomal influence on meiotic spindle assembly: abnormal meiosis I in female Mlh1 mutant mice. J Cell Biol. 1999 Jun 28;145(7):1395–1406. doi: 10.1083/jcb.145.7.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yuan L., Liu J. G., Zhao J., Brundell E., Daneholt B., Hög C. The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell. 2000 Jan;5(1):73–83. doi: 10.1016/s1097-2765(00)80404-9. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES