Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied somatic cell hybrids between thymidine kinase (EC 2.7.1.75) deficient mouse cells and human diploid fibroblasts for the expression of human acid alpha-glucosidase (EC 3.2.1.20). A deficiency in this enzyme is associated with the type II glycogenosis or Pompe disease. All 30 somatic cell hybrids selected in hypoxanthine/aminopterin/thymidine medium expressed human acid alpha-glucosidase and galactokinase (EC 2.7.1.6) and retained human chromosome 17; counterselection of the same hybrids in medium containing 5-bromodeoxyuridine resulted in the growth of hybrids that concordantly lost the expression of human acid alpha-glucosidase and galactokinase as well as human chromosome 17. Hybrids between thymidine kinase-deficient mouse cells and fibroblasts from a patient with Pompe disease that contained human chromosome 17 were found not to express human acid alpha-glucosidase. Because we have already shown that hybrids between mouse peritoneal macrophages and GM54VA simian virus 40-transformed human cells selectively retain human chromosome 17 and lose all other human chromosomes, we tested 13 independent mouse macrophage x GM54VA hybrid clones, including two that retained human chromosome 17 and no other human chromosomes, for the expression of human acid alpha-glucosidase and galactokinase. All 13 hybrid clones were found to express these human enzymes. Thus, we conclude that the gene coding for human acid alpha-glucosidase is located on human chromosome 17.
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PMID:Genetics of type II glycogenosis: assignment of the human gene for acid alpha-glucosidase to chromosome 17. 38 44

Chromosome-mediated gene transfer (CMGT) of the human genes for hypoxanthine phosphoribosyl transferase (HPRT) and cytosol thymidine kinase (TK1) into HPRT deficient mouse A9 cells or TK deficient Swiss mouse 3T3TK- cells was found to occur at frequencies at least one order of magnitude higher than DNA-mediated gene transfer (DMGT). The frequency of CMGT into 3T3TK- cells was reduced by more than an order of magnitude by a posttreatment of the recipient cells with dimethyl sulphoxide (DMSO). After CMGT, expression of the non-selected genes coding for galactokinase (GALK) and acid alpha-glucosidase (GAA), both syntenic with TK1, was observed in a number of transformants. From the pattern of cotransfer, a tentative gene ordering of CENTROMERE-GALK-TK1-GAA on human chromosome 17 was deduced. Chromosome-mediated cotransfer of X-linked human phosphoglycerate kinase (PGK) with HPRT was observed in two out of 33 A9 transformants analysed. DNA-mediated cotransfer of a syntenic gene was only observed for GALK, cotransferred with TK1 in two out of 18 TK+ transformants of mouse LTK- cells. Therefore, with murine cells as recipients of human donor genetic material, CMGT results in a higher frequency of transfer and a higher incidence of cotransfer of syntenic genes than DMGT using cellular DNA in the same cell system.
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PMID:Cotransfer of syntenic human genes into mouse cells using isolated metaphase chromosomes or cellular DNA. 388 35

The pro alpha 1 (I) collagen structural gene (COL1A1), the acid alpha-glucosidase (GAA), and the thymidine kinase (TK) genes, known to be closely linked in man (HSA) and mapped to HSA17, were found syntenic in two Cercopithecoidae species, the baboon (Papio papio, PPA) and the African green monkey (Cercopithecus aethiops, CAE) and assigned to homoeologous chromosomes, PPA16 and CAE19, respectively. The assignment of COL1A1 was obtained using two human cDNA probes. Hind III restriction sites found in man were present in the two species. The particular CAE individual used in the experiment showed a polymorphism for one DNA fragment.
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PMID:Conservation of the human COL1A1-TK-GAA synteny and homoeologous assignment in the African green monkey and the baboon (Cercopithecoidae). 609 58

We have confirmed the localization of human acid alpha-glucosidase (GAA) to 17q21----q25 and of adenosine deaminase (ADA) to 20q13----20qter by examination of hybrid clones derived from a fusion between a human cell line carrying a 17/20 balanced translocation (17pter----17q25::20q13----20qter;20pter-- --20q13::17q25----17qter) and a mouse line deficient in thymidine kinase. These hybrids were constantly maintained in HAT selective media in order to select for the presence of the human thymidine kinase gene on the intact chromosome 17 (17q21----22) or the 17/20 (17pter----17q25::20q13----20qter) translocation chromosome. We detected human GAA by rocket immunoelectrophoresis, using a heterologous antibody raised against human acid alpha-glucosidase. A clone which contained the 17/20 translocation and no intact chromosome 17 was still positive for GAA. This finding confirms the exclusion of GAA from 17q25----17qter reported by Nickel et al. (1982). Combined with earlier results (Weil et al. 1979), GAA can be assigned to 17q21----17q25. A clone which contained only the 17/20 translocation chromosome and no intact chromosome 20 contained ADA. This confirms the previous localization of ADA to 20q13.2----qter by gene dosage studies (Philip et al. 1980).
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PMID:Confirmation of the regional localization of the genes for human acid alpha-glucosidase (GAA) and adenosine deaminase (ADA) by somatic cell hybridization. 637 91

A chromosome abnormality, 46,XY,1p+, was detected in cultured amniotic fluid cells. The chromosomes of both parents were normal and it was impossible to recognise the extra chromosomal material using current banding techniques. The activity of acid alpha-glucosidase was found to be consistently higher than controls whereas activity of several other lysosomal enzymes, galactokinase and thymidine kinase was not. The results suggest that the extra material is that part of the long arm of chromosome 17 bearing the gene for acid alpha-glucosidase but not the genes for galactokinase and thymidine kinase. This would narrow the assignment of the acid alpha-glucosidase locus to 17q22 leads to 17 qter.
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PMID:Elucidation of an unbalanced chromosome translocation by gene dosage studies. 675 11

Deficiency of acid maltase (acid alpha-glucosidase), a lysosomal enzyme that degrades glycogen, results in glycogenosis type II, an autosomal recessive disease whose manifestations and severity largely depend on the level of residual enzyme activity. Previous studies have established that there are transcriptional control elements in the first intron; in particular a silencer responsive to Hes-1 and YY1 has been identified in the human hepatoma line, HepG2. This region functions as an enhancer in human fibroblasts. Here we have localized a silencer active in fibroblasts to a nearby 25-bp element in intron 1. This element repressed thymidine kinase promoter activity by about 50% in both orientations in human fibroblasts. This silencer, as with the previous one, is tissue specific since constructs containing this region are inactive in HepG2 cells. Electrophoretic mobility shift assay revealed three proteins specifically binding to the element in fibroblasts, and site-directed mutagenesis analysis indicated that all the three proteins binding to the element contribute to the silencer function. The data may be helpful for designing therapy to increase the level of enzyme, particularly when, as in most adults with the disease, there is reduced production of structurally normal enzyme.
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PMID:Identification and characterization of a tissue-specific silencer element in the first intron of the human acid maltase gene. 1151 24