Abstract
Glutamate dehydrogenase (GLUD) is a key metabolic enzyme of the mitochondrion, playing an important role in mammalian neuronal transmission. GLUD deficiency has been associated with certain forms of neurodegeneration in the human cerebellum. Genomic DNA blot hybridization analysis and identification of a large number of GLUD-specific genomic clones have suggested that human GLUD is encoded by a multigene family consisting of at least six members. A functional GLUD gene, GLUD1, has been mapped to chromosome 10q22.3-23 and a full-length “processed” GLUD gene, GLUDP1, to chromosome Xq22-23. In the context of studing the structure, the role, and the chromosomal organization of the other family members, we have analysed in detail, a cosmid clone solely reactive with the 3′ region of the GLUD cDNA. Structure and expression analysis of its GLUD-specific region suggests that it represents a truncated “processed” GLUD pseudogene. Fluorescence in situ hybridization using the entire cosmid as a probe, mapped this GLUD gene locus, termed GLUDP5, to chromosome 10p11.2.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Amuro N, Gotto Y, Okazaki T (1990) Isolation and characteriza- tion of the two distinct genes for human glutamate dehydrogenase. Biochim Biophys Acta 1049:216–218
Anagnou NP, Seuanez H, Modi WS, O'Brien SJ, Papamatheakis J, Moschonas NK (1991) Chromosomal mapping of the human glutamate dehydrogenase (GLUD) genes to chromosomes 10q22. 3-q23 and Xq22–23. Cytogenet Cell Genet 58:1947
Church G, Gilbert W (1984) Genomic sequencing. Proc Natl Acad Sci USA 81:1991–1995
Colon A, Plaitakis A, Perakis A, Berl S, Clarke DD (1986) Purification and characterization of a soluble and a particulate glutamate dehydrogenase from rat brain. J Neurochem 46:1811–1819
Dennis S, Clark JB (1978) The synthesis of glutamate by rat brain mitochondria. J Neurochem 31:673–680
Fan Y-S, Davis LM, Shows TB (1990) Mapping small DNA sequences by fluorescence in situ hybridization directly on banded metaphase chromosomes. Proc Natl Acad Sci USA 87:6223–6227
Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13
Hall C, Jacob C, Ringold G, Lee F (1983) Expression and regulation of Escherichia coli lac Z gene fusions in mammalian cells. J Mol Appl Genet 2:101–109
Hanauer A, Mattei MG, Mandel JL (1987) Presence of a TaqI polymorphism in the human glutamate dehydrogenase (GLUD) gene on chromosome 10. Nucleic Acids Res 15:6308
Herbomel P, Bourachot B, Yaniv M (1984) Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell 39:653–662
Hussain MM, Zannis VA, Plaitakis A (1989) Characterization of glutamate dehydrogenase isoproteins purified from the cerebellum of normal subjects and patients with degenerative neurological disorders, and from the human neoplastic cell lines. J Biol Chem 264:20730–20735
Jung KY, Warter S, Rumpler Y (1989) Assignment of the GDH loci to human chromosomes 10q23 and Xq24 by in situ hybridization. Ann Génét (Paris) 32:109–110
Leversha MA, Harris RM, Carter NP, Warner JP, Sargent CA, Yates JRW, Ferguson-Smith MA (1993) Gene order within 9q32-34 by fluorescence in situ hybridization on interphase nuclei. Am J Hum Genet (submitted)
Limborska S, Korneev SA, Maleeva NE, Slominsky PA, Jincharadze AG, Ivanov P, Ryskov AP (1987) Cloning of Alu-containing cDNAs from human fibroblasts and identification of small Alu+ poly(A) RNAs in a variety of human normal and tumor cells. FEBS Lett 212:208–212
Mamalaki A, Moschonas NK (1990) Aberrance and modification of α1 and α2-globin gene expression in human and mouse erythroleukemia cells. Acta haematol 84:30–37
Maniatis T, Fritch EF, Sambrook J (1982) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Mavrothalassitis G, Tzimagiorgis G, Mitsialis A, Zannis V, Plaitakis A, Papamatheakis J, Moschonas NK (1988) Isolation and characterization of cDNA clones encoding human liver glutamate dehydrogenase: evidence for a small gene family. Proc Natl Acad Sci USA 34:3494–3498
Mellon PV, Parker Y, Gluzman Y, Maniatis T (1981) Identification of DNA sequences required for transcription of the human α1-globin gene in a new SV40 host-vector system. Cell 27:279–288
Michaelidis T, Tzimagiorgis G, Moschonas NK, Papametheakis J (1993) The human glutamate dehydrogenase gene family. Gene organization and structural characterization. Genomics 16:150–160
Michelson AM, Orkin SH (1983) Boundaries of gene conversion within the duplicated human α-globin genes. J Biol Chem 258:15245–15254
Pinkel D, Straume T, Gray JW (1986) Cytogenetic analysis using quantitative, high sensitivity, fluorescence hybridization. Proc Natl Acad Sci USA 83:2934–2938
Plaitakis A, Nicklas WJ, Desnick RJ (1980) Glutamate dehydrogenase in three patients with spinocerebellar syndrome. Ann Neurol 7:297–303
Plaitakis A, Berl S, Yahr MD (1984) Neurological disorders associated with deficiency of glutamate dehydrogenase. Ann Neurol 15:144–153
Smith EL, Austen BM, Blumenthal KM, Nyc JF (1975) Glutamate dehydrogenases. In: Boyer PD (ed) The enzymes, vol 11. Academic Press, New York, pp 293–367
Tzimagiorgis G. Charlene Adamson M, Kozak CA, Moschonas NK (1991) Chromosomal mapping of glutamate dehydrogenase gene sequences to mouse chromosomes 7 and 14. Genomics 10:83–88
Weiner AM, Deininger PL, Efstratiadis A (1986) Non viral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu Rev Biochem 55:631–661
Yu AC, Schousboe A, Hertz L (1982) Metabolic fate of 14C-labeled glutamate in astrocytes in primary cultures. J Neurochem 39:954–960
Author information
Authors and Affiliations
Additional information
The nucleotide sequence reported in this paper has been submitted to the EMBL GenBANK and DDBJ Nucleotide Sequence Database under accession number X67491
Rights and permissions
About this article
Cite this article
Tzimagiorgis, G., Leversha, M.A., Chroniary, K. et al. Structure and expression analysis of a member of the human glutamate dehydrogenase (GLUD) gene family mapped to chromosome 10p11.2. Hum Genet 91, 433–438 (1993). https://doi.org/10.1007/BF00217767
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00217767