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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
MeSH Review

Gene Dosage

 
 
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Disease relevance of Gene Dosage

 

Psychiatry related information on Gene Dosage

 

High impact information on Gene Dosage

 

Chemical compound and disease context of Gene Dosage

 

Biological context of Gene Dosage

  • These data support the hypothesis that the CMT1A phenotype can result from a gene dosage effect [20].
  • In an attempt to establish the mechanisms responsible for such balanced synthesis we have altered the gene dosage for one of the components by introducing into yeast an autonomously replicating plasmid containing the gene tcm1, which codes for ribosomal protein L3 [21].
  • When two to six copies of a white promoter-Alcohol dehydrogenase (Adh) reporter fusion gene are introduced into the genome, the expression is progressively reduced both in larvae and adults rather than the expected gene dosage effect [22].
  • The results of gene dosage, complementation, and temperature-shift experiments indicate that the fates expressed by cells at successive stages of these cell lineages are specified by the level of lin-14 activity and that lin-14 acts at multiple times during development to control stage-specific choices of cell fate [23].
  • We then studied heterozygotes containing one characterized and one uncharacterized AH with particular attention to the gene copy number at the C4, Cyp21, and DRB loci [24].
 

Anatomical context of Gene Dosage

 

Associations of Gene Dosage with chemical compounds

  • DHFR gene copy numbers per cell in clones resistant to 100, 200 and 300 nM methotrexate are approximately 3, 10 and 16 times higher, respectively, than the DHFR gene copy number in the parental 3T6 cells [30].
  • Initially we analyzed examples of known gene copy number at the C4 and 21 hydroxylase loci and showed that the approach provides predictable results [24].
  • The contributions of these loci are additive, but gene dosage effects at the C5 locus are such that it largely dominates [31].
  • Glycogen synthase is almost entirely in the active, glucose 6-phosphate-independent, form in cells with increased gene dosage of GAC1 whereas the enzyme is mostly in the inactive form in strains lacking GAC1 [32].
  • The chloroquine-resistant cloned line FAC8 however, does express approximately threefold more Pgh1 protein than other isolates which is most likely because of the increased pfmdr1 gene copy number present in this isolate [33].
 

Gene context of Gene Dosage

  • Thus, we suggest that a gene dosage effect involving PMP-22 is at least partially responsible for the demyelinating neuropathy seen in CMT1A [34].
  • Gene dosage studies suggest that a high level of lin-12 activity specifies one cell fate and a low level specifies an alternative fate [35].
  • The level of H2A plus H2B protein in the cell may signal the response to histone gene copy number, suggesting that transcription of the HTA1-HTB1 locus can be autogenously regulated [36].
  • Sir2p is a limiting component in promoting yeast longevity, and increasing the gene dosage extends the life span in wild-type cells [37].
  • Gene dosage studies among ventrolateral genes suggest that the rho product (Rho) may facilitate Spi-EGF-R signaling, resulting in activation of RAS [38].
 

Analytical, diagnostic and therapeutic context of Gene Dosage

References

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  19. pfmdr1 genotyping and in vivo mefloquine resistance on the Thai-Myanmar border. Nelson, A.L., Purfield, A., McDaniel, P., Uthaimongkol, N., Buathong, N., Sriwichai, S., Miller, R.S., Wongsrichanalai, C., Meshnick, S.R. Am. J. Trop. Med. Hyg. (2005) [Pubmed]
  20. Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A. Lupski, J.R., Wise, C.A., Kuwano, A., Pentao, L., Parke, J.T., Glaze, D.G., Ledbetter, D.H., Greenberg, F., Patel, P.I. Nat. Genet. (1992) [Pubmed]
  21. Yeast use translational control to compensate for extra copies of a ribosomal protein gene. Pearson, N.J., Fried, H.M., Warner, J.R. Cell (1982) [Pubmed]
  22. Cosuppression in Drosophila: gene silencing of Alcohol dehydrogenase by white-Adh transgenes is Polycomb dependent. Pal-Bhadra, M., Bhadra, U., Birchler, J.A. Cell (1997) [Pubmed]
  23. The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events. Ambros, V., Horvitz, H.R. Genes Dev. (1987) [Pubmed]
  24. Differences in gene copy number carried by different MHC ancestral haplotypes. Quantitation after physical separation of haplotypes by pulsed field gel electrophoresis. Zhang, W.J., Degli-Esposti, M.A., Cobain, T.J., Cameron, P.U., Christiansen, F.T., Dawkins, R.L. J. Exp. Med. (1990) [Pubmed]
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  26. Elevated epidermal growth factor receptor gene copy number and expression in a squamous carcinoma cell line. Merlino, G.T., Xu, Y.H., Richert, N., Clark, A.J., Ishii, S., Banks-Schlegel, S., Pastan, I. J. Clin. Invest. (1985) [Pubmed]
  27. Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders. Passamonti, F., Rumi, E., Pietra, D., Della Porta, M.G., Boveri, E., Pascutto, C., Vanelli, L., Arcaini, L., Burcheri, S., Malcovati, L., Lazzarino, M., Cazzola, M. Blood (2006) [Pubmed]
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  35. The lin-12 locus specifies cell fates in Caenorhabditis elegans. Greenwald, I.S., Sternberg, P.W., Horvitz, H.R. Cell (1983) [Pubmed]
  36. A yeast H2A-H2B promoter can be regulated by changes in histone gene copy number. Moran, L., Norris, D., Osley, M.A. Genes Dev. (1990) [Pubmed]
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