genetic nondisjunction

Summary

Summary: The failure of homologous CHROMOSOMES or CHROMATIDS to segregate during MITOSIS or MEIOSIS with the result that one daughter cell has both of a pair of parental chromosomes or chromatids and the other has none.

Top Publications

  1. Lamb N, Hassold T. Nondisjunction--a view from ringside. N Engl J Med. 2004;351:1931-4 pubmed
  2. Hodges C, Revenkova E, Jessberger R, Hassold T, Hunt P. SMC1beta-deficient female mice provide evidence that cohesins are a missing link in age-related nondisjunction. Nat Genet. 2005;37:1351-5 pubmed
    ..Additionally, our observations support the hypothesis that deficient cohesion is an underlying cause of human age-related aneuploidy...
  3. Arya G, Lodico M, Ahmad O, Amin R, Tomkiel J. Molecular characterization of teflon, a gene required for meiotic autosome segregation in male Drosophila melanogaster. Genetics. 2006;174:125-34 pubmed publisher
    ..On the basis of these findings, we propose a role for Tef as a bridging molecule that holds autosome bivalents together via heterochromatic connections...
  4. Thomas S, Soltani Bejnood M, Roth P, Dorn R, Logsdon J, McKee B. Identification of two proteins required for conjunction and regular segregation of achiasmate homologs in Drosophila male meiosis. Cell. 2005;123:555-68 pubmed
    ..SNM and MNM do not colocalize with SMC1, suggesting that the homolog conjunction mechanism is independent of cohesin...
  5. Shi Q, King R. Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines. Nature. 2005;437:1038-42 pubmed
    ..The coupling of spontaneous segregation errors to furrow regression provides a potential explanation for the prevalence of hyperdiploid chromosome number and centrosome amplification observed in many cancers...
  6. Lamb N, Sherman S, Hassold T. Effect of meiotic recombination on the production of aneuploid gametes in humans. Cytogenet Genome Res. 2005;111:250-5 pubmed
    ..Future studies are expected to shed new light on the timing and placement of recombination, providing additional clues to the link between altered recombination and chromosome nondisjunction...
  7. Marston A, Tham W, Shah H, Amon A. A genome-wide screen identifies genes required for centromeric cohesion. Science. 2004;303:1367-70 pubmed
    ..The screen described here provides a comprehensive analysis of the genes required for the meiotic cell cycle and identifies three factors important for the stepwise loss of sister chromatid cohesion...
  8. Harris D, Orme C, Kramer J, Namba L, Champion M, Palladino M, et al. A deficiency screen of the major autosomes identifies a gene (matrimony) that is haplo-insufficient for achiasmate segregation in Drosophila oocytes. Genetics. 2003;165:637-52 pubmed
  9. Whyte W, Irick H, Arbel T, Yasuda G, French R, Falk D, et al. The genetic analysis of achiasmate segregation in Drosophila melanogaster. III. The wild-type product of the Axs gene is required for the meiotic segregation of achiasmate homologs. Genetics. 1993;134:825-35 pubmed
    ..In the absence of Axs+ function, the homologs are often unable to separate from each other and behave as a single segregational unit that is free to segregate from heterologous chromosomes...

More Information

Publications62

  1. Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2:280-91 pubmed
    ..However, recent molecular and cytogenetic approaches are now beginning to shed light on the non-disjunctional processes that lead to aneuploidy...
  2. Weaver B, Silk A, Cleveland D. Cell biology: nondisjunction, aneuploidy and tetraploidy. Nature. 2006;442:E9-10; discussion E10 pubmed
    ..We suggest that chromatin trapped in the cytokinetic cleavage furrow is the more likely reason for furrow regression and tetraploidization...
  3. Hirai K, Toyohira S, Ohsako T, Yamamoto M. Isolation and cytogenetic characterization of male meiotic mutants of Drosophila melanogaster. Genetics. 2004;166:1795-806 pubmed
    ..mei(2)yh92 predominantly induced nondisjunction at meiosis I that appeared to be the consequence of failure of the separation of paired homologous chromosomes...
  4. Yu K, Feingold E. Methods for analyzing the spatial distribution of chiasmata during meiosis based on recombination data. Biometrics. 2002;58:369-77 pubmed
    ..We apply our improved methods to reanalyze a dataset from the literature studying the association between crossover location and meiotic nondisjunction of chromosome 21...
  5. Sekelsky J, McKim K, Messina L, French R, Hurley W, Arbel T, et al. Identification of novel Drosophila meiotic genes recovered in a P-element screen. Genetics. 1999;152:529-42 pubmed
    ..Although most of these are alleles of previously undescribed genes, five were in the known genes alphaTubulin67C, CycE, push, and Trl. The five mutations in known genes produce novel phenotypes for those genes...
  6. Robinson W, Kuchinka B, Bernasconi F, Petersen M, Schulze A, Brondum Nielsen K, et al. Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal age effect on level of recombination. Hum Mol Genet. 1998;7:1011-9 pubmed
    ..However, they may also reflect the presence of multiple factors which act to ensure normal segregation, each affected by maternal age in a different way and varying in importance for each chromosome...
  7. Hawley R, Irick H, Zitron A, Haddox D, Lohe A, New C, et al. There are two mechanisms of achiasmate segregation in Drosophila females, one of which requires heterochromatic homology. Dev Genet. 1992;13:440-67 pubmed
    ..elegans males. We also suggest that the physical basis of this process may reflect known properties of the Drosophila meiotic spindle...
  8. Zhang P, Hawley R. The genetic analysis of distributive segregation in Drosophila melanogaster. II. Further genetic analysis of the nod locus. Genetics. 1990;125:115-27 pubmed
    ..Thus, either the nod locus defines a function that is specific to distributive segregation or exchange can fully compensate for the absence of the nod+ function...
  9. Zitron A, Hawley R. The genetic analysis of distributive segregation in Drosophila melanogaster. I. Isolation and characterization of Aberrant X segregation (Axs), a mutation defective in chromosome partner choice. Genetics. 1989;122:801-21 pubmed
    ..In addition to its dramatic effects on the X chromosome, Axs exerts a similar effect on the segregation of a major autosome. We conclude that Axs defines a locus required for proper homolog disjunction within the distributive system...
  10. Carpenter A. Chiasma function. Cell. 1994;77:957-62 pubmed
  11. Bugge M, Collins A, Petersen M, Fisher J, Brandt C, Hertz J, et al. Non-disjunction of chromosome 18. Hum Mol Genet. 1998;7:661-9 pubmed
    ..We extend this study to examine the remaining autosomes and find no evidence for normal disjunction from nullichiasmate tetrads generally...
  12. Tease C, Fisher G. Two new X-autosome Robertsonian translocations in the mouse. I. Meiotic chromosome segregation in male hemizygotes and female heterozygotes. Genet Res. 1991;58:115-21 pubmed
  13. Lamb N, Yu K, Shaffer J, Feingold E, Sherman S. Association between maternal age and meiotic recombination for trisomy 21. Am J Hum Genet. 2005;76:91-9 pubmed
    ..It is this risk, due to recombination-independent factors, that would be most influenced by increasing age, leading to the observed maternal age effect...
  14. Jeffreys C, Burrage P, Bickel S. A model system for increased meiotic nondisjunction in older oocytes. Curr Biol. 2003;13:498-503 pubmed
  15. Karpen G, Le M, Le H. Centric heterochromatin and the efficiency of achiasmate disjunction in Drosophila female meiosis. Science. 1996;273:118-22 pubmed
    ..How heterochromatin could act to promote chromosome pairing is discussed here...
  16. Thomas N, Ennis S, Sharp A, Durkie M, Hassold T, Collins A, et al. Maternal sex chromosome non-disjunction: evidence for X chromosome-specific risk factors. Hum Mol Genet. 2001;10:243-50 pubmed
    ..Thus, surprisingly, the risk factors associated with both MI and MII non-disjunction appear to be different for virtually every chromosome that has been adequately studied...
  17. Koehler K, Boulton C, Collins H, French R, Herman K, Lacefield S, et al. Spontaneous X chromosome MI and MII nondisjunction events in Drosophila melanogaster oocytes have different recombinational histories. Nat Genet. 1996;14:406-14 pubmed
    ..MII nondisjunction occurred only in oocytes with proximal exchanges. We propose several models to explain how very proximal exchanges might impair proper segregation...
  18. Komma D, Endow S. Enhancement of the ncdD microtubule motor mutant by mutants of alpha Tub67C. J Cell Sci. 1997;110 ( Pt 2):229-37 pubmed
    ..These results imply that a specific alpha-tubulin isoform is required for normal cellular function of a kinesin motor protein...
  19. Knowles B, Hawley R. Genetic analysis of microtubule motor proteins in Drosophila: a mutation at the ncd locus is a dominant enhancer of nod. Proc Natl Acad Sci U S A. 1991;88:7165-9 pubmed
    ..The probability that the distributive system will fail is enhanced in females simultaneously haploinsufficient at the nod and ncd loci...
  20. Tease C, Hartshorne G, Hultén M. Patterns of meiotic recombination in human fetal oocytes. Am J Hum Genet. 2002;70:1469-79 pubmed
    ..We speculate that these abnormal fetal oocytes may be the source of the nonrecombinant chromosomes 13 and X suggested, by genetic studies, to be associated with maternally derived chromosome nondisjunction...
  21. Hawley R, Theurkauf W. Requiem for distributive segregation: achiasmate segregation in Drosophila females. Trends Genet. 1993;9:310-7 pubmed
    ..The other system facilitates the segregation of heterologous chromosomes, by an as yet undiscovered mechanism...
  22. Underkoffler L, Mitchell L, Localio A, Marchegiani S, Morabito J, Collins J, et al. Molecular analysis of nondisjunction in mice heterozygous for a Robertsonian translocation. Genetics. 2002;161:1219-24 pubmed
    ..These results show that molecular genotyping provides a valuable tool for understanding factors influencing meiotic nondisjunction in mammals...
  23. Tang T, Bickel S, Young L, Orr Weaver T. Maintenance of sister-chromatid cohesion at the centromere by the Drosophila MEI-S332 protein. Genes Dev. 1998;12:3843-56 pubmed
  24. Malmanche N, Owen S, Gegick S, Steffensen S, Tomkiel J, Sunkel C. Drosophila BubR1 is essential for meiotic sister-chromatid cohesion and maintenance of synaptonemal complex. Curr Biol. 2007;17:1489-97 pubmed
    ..Our results demonstrate that BubR1 is essential to maintain sister-chromatid cohesion during meiotic progression in both sexes and for normal maintenance of SC in females...
  25. Soltani Bejnood M, Thomas S, Villeneuve L, Schwartz K, Hong C, McKee B. Role of the mod(mdg4) common region in homolog segregation in Drosophila male meiosis. Genetics. 2007;176:161-80 pubmed
  26. Mamon L, Komarova A, Bondarenko L, Barabanova L, Tikhomirova M. [Development of thermotolerance in Drosophila melanogaster line l(1) ts403 with a defect in heat shock protein synthesis]. Genetika. 1998;34:920-8 pubmed
  27. Keefe D, Liu L, Marquard K. Telomeres and aging-related meiotic dysfunction in women. Cell Mol Life Sci. 2007;64:139-43 pubmed
    ..This has led to a telomere theory of age-related meiotic dysfunction in women, and underlined the importance to human health of a mechanistic understanding of telomeres and meiosis...
  28. Schon E, Kim S, Ferreira J, Magalhaes P, Grace M, Warburton D, et al. Chromosomal non-disjunction in human oocytes: is there a mitochondrial connection?. Hum Reprod. 2000;15 Suppl 2:160-72 pubmed
    ..This hypothesis would explain many of the non-Mendelian features associated with maternal age-related trisomies, e.g. Down's syndrome...
  29. Muñoz E, Barnett B. Chromosome malsegregation induced by the rodent carcinogens acetamide, pyridine and diethanolamine in Drosophila melanogaster females. Mutat Res. 2003;539:137-44 pubmed
    ..AC and DEA (the most active of the three) induced similar frequencies of nondisjunction in all broods suggesting unspecific cell division perturbations probably due to toxicity. No clear dose effect relationships were observed...
  30. Hawley R. Human meiosis: model organisms address the maternal age effect. Curr Biol. 2003;13:R305-7 pubmed
    ..Moreover, the demonstration of a meiotic aneugen in mice provides important clues to the higher frequencies of nondisjunction observed in older women...
  31. Hartway S. A parent's guide to the genetics of Down syndrome. Adv Neonatal Care. 2009;9:27-30 pubmed publisher
  32. Koehler K, Hassold T. Human aneuploidy: lessons from achiasmate segregation in Drosophila melanogaster. Ann Hum Genet. 1998;62:467-79 pubmed
    ..Drawing upon observations made in flies, we also propose a new model for the segregation of achiasmate chromosomes in humans...
  33. Yang A, Kaushal D, Rehen S, Kriedt K, Kingsbury M, McConnell M, et al. Chromosome segregation defects contribute to aneuploidy in normal neural progenitor cells. J Neurosci. 2003;23:10454-62 pubmed
    ..These data independently confirm the presence of aneuploid NPCs and demonstrate the occurrence of mitotic segregation defects in normal cells that can mechanistically account for aneuploidy in the CNS...
  34. Ohkura H, Kinoshita N, Miyatani S, Toda T, Yanagida M. The fission yeast dis2+ gene required for chromosome disjoining encodes one of two putative type 1 protein phosphatases. Cell. 1989;57:997-1007 pubmed
    ..These dis2+ and similar polypeptides of yeasts and mouse are found to be highly homologous (75%-90% identical) to rabbit protein phosphatase 1. The implications of these findings are discussed with regard to mitotic control...
  35. Zhao H, Li J, Robinson W. Multipoint genetic mapping with uniparental disomy data. Am J Hum Genet. 2000;67:851-61 pubmed
    ..The proposed method has been implemented in a computer program, and we illustrate the proposed approach through its application to a set of UPD15 data...
  36. Favor J, Neuhauser Klaus A. Loss of heterozygosity at the dilute-short ear (Myo5a-Bmp5) region of the mouse: mitotic recombination or double non-disjunction?. Genet Res. 1998;72:199-204 pubmed
    ..Our results indicate the mutational event to be due to mitotic recombination and not double non-disjunction...
  37. Machatkova M, Brouckova M, Matejckova M, Krebsova A, Sperling K, Vorsanova S, et al. QF-PCR examination of parental and meiotic origin of trisomy 21 in Central and Eastern Europe. J Histochem Cytochem. 2005;53:371-3 pubmed
    ..4% and 14.3% and paternal in 3.1% and 5.7% in Ukraine and Russia, respectively. No significant differences were found in maternal/paternal origin among Ukraine, Russia, Germany, and published data from other European regions...
  38. Borodin P. Speciation and centromere evolution. Science. 2001;294:2478-80 pubmed
  39. Thomas N, Collins A, Hassold T, Jacobs P. A reinvestigation of non-disjunction resulting in 47, XXY males of paternal origin. Eur J Hum Genet. 2000;8:805-8 pubmed
    ..This failure was not associated with the presence of an increase in recombination in the smaller Xq/Yq pseudoautosomal region (PAR 2) or with the presence of microdeletions within PAR 1...
  40. Muñoz E, Barnett B. Evaluation of the genotoxicity of aniline.HCl in Drosophila melanogaster. Mutat Res. 1998;413:15-22 pubmed
    ..No sex-linked lethals or translocations were induced...
  41. Arnold S, Pelet A, Amiel J, Borrego S, Hofstra R, Tam P, et al. Interaction between a chromosome 10 RET enhancer and chromosome 21 in the Down syndrome-Hirschsprung disease association. Hum Mutat. 2009;30:771-5 pubmed publisher
    ..This is the first report of a genetic interaction between a common functional variant (rs2435357) and a not infrequent copy number error (chromosome 21 dosage) in two human developmental disorders...
  42. Turleau C, Vekemans M. [Trisomy 21: fifty years between medicine and science]. Med Sci (Paris). 2010;26:267-72 pubmed publisher
    ..The recent description of metabolic pathways controlled by RCAN1 and DYRK1A genes which may be involved in many biological processes and phenotypes associated with trisomy 21 allows to consider new therapeutic strategies...
  43. de Sant Anna J, Franco C, Miyamoto C, Cunico M, Miguel O, Côcco L, et al. Genotoxicity of Achillea millefolium essential oil in diploid cells of Aspergillus nidulans. Phytother Res. 2009;23:231-5 pubmed publisher
    ..19 microL/mL and 0.25 microL/mL concentrations. The genotoxicity of the oil was associated with the induction of mitotic non-disjunction or crossing-over by oil...
  44. Shonn M, Murray A, Murray A. Spindle checkpoint component Mad2 contributes to biorientation of homologous chromosomes. Curr Biol. 2003;13:1979-84 pubmed
  45. Rudd M, Mays R, Schwartz S, Willard H. Human artificial chromosomes with alpha satellite-based de novo centromeres show increased frequency of nondisjunction and anaphase lag. Mol Cell Biol. 2003;23:7689-97 pubmed
    ..As different artificial chromosomes missegregate over a fivefold range, the data suggest that variable centromeric DNA content and/or epigenetic assembly can influence the mitotic behavior of artificial chromosomes...
  46. Calogero A, Burrello N, De Palma A, Barone N, D Agata R, Vicari E. Sperm aneuploidy in infertile men. Reprod Biomed Online. 2003;6:310-7 pubmed
    ..Thus, sperm aneuploidy evaluation is recommended in infertile patients with abnormal semen parameters, particularly if they undergo IVF programmes...
  47. Vogels A, Matthijs G, Legius E, Devriendt K, Fryns J. Chromosome 15 maternal uniparental disomy and psychosis in Prader-Willi syndrome. J Med Genet. 2003;40:72-3 pubmed
  48. Li J, Sherman S, Lamb N, Zhao H. Multipoint genetic mapping with trisomy data. Am J Hum Genet. 2001;69:1255-65 pubmed
    ..We illustrate the proposed approaches through their application to a set of trisomy 21 data...
  49. Apionishev S, Malhotra D, Raghavachari S, Tanda S, Rasooly R. The Drosophila UBC9 homologue lesswright mediates the disjunction of homologues in meiosis I. Genes Cells. 2001;6:215-24 pubmed
    ..In Saccharomyces cerevisiae and other organisms, the UBC9 (ubiquitin-conjugating 9) protein modifies the function of many different target proteins through covalent attachment of the ubiquitin-like protein SMT-3/SUMO...
  50. Rasooly R, New C, Zhang P, Hawley R, Baker B. The lethal(1)TW-6cs mutation of Drosophila melanogaster is a dominant antimorphic allele of nod and is associated with a single base change in the putative ATP-binding domain. Genetics. 1991;129:409-22 pubmed
    ..We propose that the defective protein encoded by the nodDTW allele interferes with proper chromosome movement during both meiosis and mitosis, perhaps by binding irreversibly to microtubules...
  51. Biron Shental T, Amiel A, Fejgin M. Previous aneuploidic offspring in a young woman does not increase the risk for somatic random aneuploidy in subsequent pregnancies. Acta Obstet Gynecol Scand. 2006;85:1003-7 pubmed
    ..There was no significant difference in the rate of aneuploidy of both chromosomes between the study and control groups. However, this rate was significantly higher in the aneuploid pregnancies (p < 0.05)...
  52. Torres Rosell J, De Piccoli G, Cordon Preciado V, Farmer S, Jarmuz A, Machin F, et al. Anaphase onset before complete DNA replication with intact checkpoint responses. Science. 2007;315:1411-5 pubmed
    ..We propose that the completion of replication is not under the surveillance of known checkpoints...
  53. Hunt P, Jackson J, Horan S, Lawson C, Grindell L, Washburn L, et al. The mouse A/HeJ Y chromosome: another good Y gone bad. Chromosome Res. 2008;16:623-36 pubmed publisher
    ..We conclude that these centromeric features make the human and mouse Y chromosomes extremely sensitive to minor structural alterations, and that our studies provide yet another example of a good Y chromosome gone 'bad.'..