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Disease relevance of Diploidy


High impact information on Diploidy

  • Epigenetic silencing of FLO11 regulates a key developmental switch: when FLO11 is expressed, diploid cells form pseudohyphal filaments; when FLO11 is silent, the cells grow in yeast form [6].
  • These results demonstrate a role for the region 3' to Xist exon 6 in the counting process and suggest that counting is mediated by a repressive mechanism which prevents inactivation of a single X chromosome in diploid cells [7].
  • The lines, mainly of erythroid or myelomonocytic origin, were diploid but highly tumorigenic from their inception [8].
  • Cells retaining one wild-type p53 allele mimicked the behavior of primary diploid cells: they arrested growth in the presence of drug and failed to demonstrate amplification [9].
  • They also have found a meiotic level of message in temperature-sensitive cdc25 diploids shifted to high temperature in rich medium (Simchen and Kassir, 1989) [10].

Chemical compound and disease context of Diploidy


Biological context of Diploidy

  • GPA1 transcript was found in haploid cells but was not detected in diploid cells [16].
  • Unlike the wild-type diploid cells, the cyr1 and CYR3 homozygous diploid cells were capable of initiating meiosis even in nutrient growth media [17].
  • A smaller subfragment, when used to direct integration of a plasmid to the benomyl resistance locus in a diploid cell, disrupted one of the beta-tubulin genes and concomitantly created a recessive lethal mutation, indicating that the single beta-tubulin gene of yeast has an essential function [18].
  • Antibody response to preexposure human diploid-cell rabies vaccine given concurrently with chloroquine [19].
  • The use of the polymerase chain reaction for analysing DNA sequences in individual diploid cells and human sperm shows that two genetic loci can be co-amplified from a single sperm, which may allow the analysis of previously inaccessible genetic phenomena [20].

Anatomical context of Diploidy


Associations of Diploidy with chemical compounds

  • Of 17 evaluable patients with unresectable hyperdiploid tumors, 15 had complete responses and two had partial responses to cyclophosphamide and doxorubicin; six others with diploid tumors did not respond (P = 0.00001) [26].
  • Deletion of the diploid dihydrofolate reductase locus from cultured mammalian cells [27].
  • To facilitate studies of folate metabolism and chemotherapy the sole dhfr-ts copy in a heterozygous deletion line was replaced, yielding lines that were functionally DHFR-TS-. Although most genes are diploid in trypanosomatids, methods exploiting the high frequency of homologous recombination should permit complete replacement of any parasite gene [28].
  • Here it was shown that in diploids some of the same kinases and STE12 are required for filamentous growth, but the pheromone receptors and guanosine triphosphate-binding protein are not required for filament formation [29].
  • Polyinosinic.polycytidylic acid [poly(I.C)] induced production of interferon by a strain of diploid human fibroblasts (FS-4), measured between 5 and 24 hours from induction, is enhanced up to 128-fold by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a reversible inhibitor of nuclear heterogeneous RNA synthesis [30].

Gene context of Diploidy

  • Starvation for nitrogen further induced (6- to 8-fold) transcription of IME1, but, as expected, the induction was found only in MATa/MAT alpha or rme1-1/rme1-1 diploids [31].
  • However, ras1 - ras2 - spores of doubly heterozygous diploids are incapable of resuming vegetative growth [32].
  • Control of the initiation of meiosis was examined in diploids of yeast homozygous for two temperature-sensitive mutations, cyr1 and CYR3, which are defective in adenylate cyclase and cAMP-dependent protein kinase, respectively [17].
  • Furthermore, ubi4/ubi4 diploids are sporulation-defective. ubi4 mutants are also hypersensitive to high temperatures, starvation, and amino acid analogs [33].
  • We also studied the sporulation products of a diploid heterozygous at the HIS4 locus for an insertion of a 100 bp fragment of MATa containing the HO endonuclease cut site [34].

Analytical, diagnostic and therapeutic context of Diploidy


  1. DNA immunization protects nonhuman primates against rabies virus. Lodmell, D.L., Ray, N.B., Parnell, M.J., Ewalt, L.C., Hanlon, C.A., Shaddock, J.H., Sanderlin, D.S., Rupprecht, C.E. Nat. Med. (1998) [Pubmed]
  2. Transformation of rat liver epithelial cells by Kirsten murine sarcoma virus. Rhim, J.S., Kim, C.M., Okigaki, T., Huebner, R.J. J. Natl. Cancer Inst. (1977) [Pubmed]
  3. Stabilized non-complementing diploids (Ncd) from fused protoplast products of B. subtilis. Guillén, N., Amar, M., Hirschbein, L. EMBO J. (1985) [Pubmed]
  4. Failed retrograde transport of NGF in a mouse model of Down's syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion. Cooper, J.D., Salehi, A., Delcroix, J.D., Howe, C.L., Belichenko, P.V., Chua-Couzens, J., Kilbridge, J.F., Carlson, E.J., Epstein, C.J., Mobley, W.C. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  5. X-ray sensitivity of diploid fibroblasts from patients with hereditary or sporadic retinoblastoma. Weichselbaum, R.R., Nove, J., Little, J.B. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  6. Genetic and epigenetic regulation of the FLO gene family generates cell-surface variation in yeast. Halme, A., Bumgarner, S., Styles, C., Fink, G.R. Cell (2004) [Pubmed]
  7. Role of the region 3' to Xist exon 6 in the counting process of X-chromosome inactivation. Clerc, P., Avner, P. Nat. Genet. (1998) [Pubmed]
  8. Absence of p53 allows direct immortalization of hematopoietic cells by the myc and raf oncogenes. Metz, T., Harris, A.W., Adams, J.M. Cell (1995) [Pubmed]
  9. Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Livingstone, L.R., White, A., Sprouse, J., Livanos, E., Jacks, T., Tlsty, T.D. Cell (1992) [Pubmed]
  10. Dual regulation of meiosis in yeast. Malone, R.E. Cell (1990) [Pubmed]
  11. Comparative genomic hybridization of formalin-fixed, paraffin-embedded breast tumors reveals different patterns of chromosomal gains and losses in fibroadenomas and diploid and aneuploid carcinomas. Ried, T., Just, K.E., Holtgreve-Grez, H., du Manoir, S., Speicher, M.R., Schröck, E., Latham, C., Blegen, H., Zetterberg, A., Cremer, T. Cancer Res. (1995) [Pubmed]
  12. Alkyl methane sulfonate mutation of diploid human lymphoblasts and Salmonella typhimurium. Hoppe, H., Skopeck, T.R., Liber, H.L., Thilly, W.G. Cancer Res. (1978) [Pubmed]
  13. Induction of syncytia by the bovine C-type leukemia virus. Diglio, C.A., Ferrer, J.F. Cancer Res. (1976) [Pubmed]
  14. Diversity in intrinsic strengths of the human complement system: serum C4 protein concentrations correlate with C4 gene size and polygenic variations, hemolytic activities, and body mass index. Yang, Y., Chung, E.K., Zhou, B., Blanchong, C.A., Yu, C.Y., Füst, G., Kovács, M., Vatay, A., Szalai, C., Karádi, I., Varga, L. J. Immunol. (2003) [Pubmed]
  15. Monoclonal antibody-based, selective isolation of DNA fragments containing an alkylated base to be quantified in defined gene sequences. Hochleitner, K., Thomale, J., Nikitin AYu, n.u.l.l., Rajewsky, M.F. Nucleic Acids Res. (1991) [Pubmed]
  16. GPA1, a haploid-specific essential gene, encodes a yeast homolog of mammalian G protein which may be involved in mating factor signal transduction. Miyajima, I., Nakafuku, M., Nakayama, N., Brenner, C., Miyajima, A., Kaibuchi, K., Arai, K., Kaziro, Y., Matsumoto, K. Cell (1987) [Pubmed]
  17. Initiation of meiosis in yeast mutants defective in adenylate cyclase and cyclic AMP-dependent protein kinase. Matsumoto, K., Uno, I., Ishikawa, T. Cell (1983) [Pubmed]
  18. Isolation of the beta-tubulin gene from yeast and demonstration of its essential function in vivo. Neff, N.F., Thomas, J.H., Grisafi, P., Botstein, D. Cell (1983) [Pubmed]
  19. Antibody response to preexposure human diploid-cell rabies vaccine given concurrently with chloroquine. Pappaioanou, M., Fishbein, D.B., Dreesen, D.W., Schwartz, I.K., Campbell, G.H., Sumner, J.W., Patchen, L.C., Brown, W.J. N. Engl. J. Med. (1986) [Pubmed]
  20. Amplification and analysis of DNA sequences in single human sperm and diploid cells. Li, H.H., Gyllensten, U.B., Cui, X.F., Saiki, R.K., Erlich, H.A., Arnheim, N. Nature (1988) [Pubmed]
  21. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Blau, H.M., Chiu, C.P., Webster, C. Cell (1983) [Pubmed]
  22. Possible positive autocrine feedback in the prereplicative phase of human fibroblasts. Paulsson, Y., Hammacher, A., Heldin, C.H., Westermark, B. Nature (1987) [Pubmed]
  23. Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression. Bargou, R.C., Jürchott, K., Wagener, C., Bergmann, S., Metzner, S., Bommert, K., Mapara, M.Y., Winzer, K.J., Dietel, M., Dörken, B., Royer, H.D. Nat. Med. (1997) [Pubmed]
  24. Inviability of parthenogenones is determined by pronuclei, not egg cytoplasm. Mann, J.R., Lovell-Badge, R.H. Nature (1984) [Pubmed]
  25. Multiple human beta interferon genes. Sagar, A.D., Sehgal, P.B., Slate, D.L., Ruddle, F.H. J. Exp. Med. (1982) [Pubmed]
  26. Cellular DNA content as a predictor of response to chemotherapy in infants with unresectable neuroblastoma. Look, A.T., Hayes, F.A., Nitschke, R., McWilliams, N.B., Green, A.A. N. Engl. J. Med. (1984) [Pubmed]
  27. Deletion of the diploid dihydrofolate reductase locus from cultured mammalian cells. Urlaub, G., Käs, E., Carothers, A.M., Chasin, L.A. Cell (1983) [Pubmed]
  28. Gene replacement in parasitic protozoa. Cruz, A., Beverley, S.M. Nature (1990) [Pubmed]
  29. Elements of the yeast pheromone response pathway required for filamentous growth of diploids. Liu, H., Styles, C.A., Fink, G.R. Science (1993) [Pubmed]
  30. Human interferon production: superinduction by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole. Sehgal, P.B., Tamm, I., Vilcek, J. Science (1975) [Pubmed]
  31. IME1, a positive regulator gene of meiosis in S. cerevisiae. Kassir, Y., Granot, D., Simchen, G. Cell (1988) [Pubmed]
  32. Genetic analysis of yeast RAS1 and RAS2 genes. Kataoka, T., Powers, S., McGill, C., Fasano, O., Strathern, J., Broach, J., Wigler, M. Cell (1984) [Pubmed]
  33. The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation, and other stresses. Finley, D., Ozkaynak, E., Varshavsky, A. Cell (1987) [Pubmed]
  34. Double-strand breaks can initiate meiotic recombination in S. cerevisiae. Kolodkin, A.L., Klar, A.J., Stahl, F.W. Cell (1986) [Pubmed]
  35. Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry. Clark, G.M., Dressler, L.G., Owens, M.A., Pounds, G., Oldaker, T., McGuire, W.L. N. Engl. J. Med. (1989) [Pubmed]
  36. Spontaneous neurinoma in an African lungfish, Protopterus annectens, and DNA repair studies on normal and neoplastic tissues. Ishikawa, T., Masahito, P., Nemoto, N., Matsumoto, J., Shima, A. J. Natl. Cancer Inst. (1986) [Pubmed]
  37. Growth-dependent alterations in oligomannosyl cores of glycopeptides. Ceccarini, C., Muramatsu, T., Tsang, J., Atkinson, P.H. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  38. Rapid clonal growth and serial passage of human diploid fibroblasts in a lipid-enriched synthetic medium supplemented with epidermal growth factor, insulin, and dexamethasone. Bettger, W.J., Boyce, S.T., Walthall, B.J., Ham, R.G. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  39. Human heterozygosity: a new estimate. McConkey, E.H., Taylor, B.J., Phan, D. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
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