Summary
Catechol-O-methyltransferase (COMT) plays an important role in the inactivation of catecholamines. It has been demonstrated that erythrocyte COMT activity is genetically determined and controlled by a major autosomal locus with two alleles. The recent development of a method which allows the detection of COMT isozymes directly in autoradiozymograms has provided the means to investigate the chromosome location of the gene by using somatic cell hybrids. We have found that a single form of the COMT enzyme is expressed in several mouse-human fibroblast cell lines. The data obtained from the segregation analysis of the COMT enzyme in these hybrids and their subclones have provided evidence for the location of a major gene for COMT activity on human chromosome 22.
Similar content being viewed by others
References
Axelrod J (1966) Methylation reactions in the formation and metabolism of catecholamines and other biogenic amines. Pharmacol Rev 18:95–113
Axelrod J, Cohn CK (1971) Methyltransferase enzymes in red blood cells. J Pharmacol Exp Ther 176:650–654
Axelrod J, Tomchick R (1958) Enzymatic o-methylation of epinephrine and other catechols. J Biol Chem 233:702–705
Axelrod J, Vesell ES (1970) Heterogeneity of N- and O-methyltransferases. Mol Pharmacol 6:78
Brahe C, Serra A (1981) A simple method for fusing human lymphocytes with rodent cells in monolayer by polyethylene glycol. Somatic Cell Genet 7:109–115
Brahe C, Crosti N, Meera Khan P, Serra A (1984) Catechol-O-methyltransferase: a method for autoradiographic visualization of isozymes in Cellogel. Biochem Genet 22:125–132
Brahe C, Serra A, Morton NE (1985) Erythrocyte catechol-O-methyltransferase activity: genetic analysis in nuclear families with one child affected by Down syndrome. Am J Med Genet 21:373–384
Brahe C, Bannetta P, Serra A, Arwert F (1986) Letter to the Editor: the increased COMT activity in Down syndrome patients is not a consequence of dosage effect owing to location of the gene on chromosome 21: further evidence. Am J Med Genet 24:203–204
Floderus Y, Wetterberg L (1981) The inheritance of human erythrocyte catechol-O-methyltransferase activity. Clin Genet 19:392–395
Floderus Y, Ross SB, Wetterberg L (1981) Erythrocyte catechol-O-methyltransferase activity in a Swedish population. Clin Genet 19:389–392
Floderus Y, Iselius L, Lindsten J, Wetterberg L (1982) Evidence for a major locus as well as a multifactorial component in the regulation of human red blood cell catechol-O-methyltransferase activity. Hum Hered 32:76–79
Goldin LR, Gershon ES, Lake CR, Murphy DL, McGinniss M, Sparkes RS (1982) Segregation and linkage studies of plasma dopamine-beta-hydroxylase (DBH), erythrocyte catechol-O-methyltransferase (COMT), and platelet monoamine oxidase (MAO): possible linkage between the ABO locus and a gene controlling DBH activity. Am J Hum Genet 34:250–262
Goldin LR (1985) Segregation analysis of dopamine-beta-hydroxylase (DBH) and catechol-O-methyltransferase (COMT): identification of major locus and polygenic components. Genet Epidemiol 2: 317–325
Gustavson KH, Wetterberg L, Bäckström M, Ross SB (1973) Catechol-O-methyltransferase activity in erythrocytes in Down's syndrome. Clin Genet 4:279–280
Herbschleb-Voogt E, Grzeschik KH, Pearson PL, Meera Khan P (1981) Assignment of adenosine deaminase complexing protein (ADCP) gene(s) to human chromosome 2 in rodent-human somatic cell hybrids. Hum Genet 59:317–323
Jacobowitz DM (1972) Localization of catechol-O-methyltransferase and monoamine oxidase in fibroblasts in tissue culture. Life Sci 11:965–974
Meera Khan P (1971) Enzyme electrophoresis on cellulose acetate gel. Zymogram patterns in man-mouse and man-Chinese hamster somatic cell hybrids. Arch Biochem Biophys 145:470–483
Perry P, Wolff S (1974) New Giemsa method for the differential staining of sister chromatids. Nature 251:156–158
Pontecorvo G (1975) Production of mammalian somatic cell hybrids by means of polyethylene glycol treatment. Somatic Cell Genet 1:391–395
Scanlon PD, Raymond FA, Weinshilboum RM (1979) Catechol-O-methyltransferase: thermolabile enzyme in erythrocytes of subjects homozygous for allele for low activity. Science 203:63–65
Seabright M (1971) A rapid banding technique for human chromosomes. Lancet II:971–972
Siervogel RM, Weinshilboum R, Wilson AF, Elston RC (1984) Major gene model for the inheritance of catechol-O-methyltransferase activity in five large families. Am J Med Genet 19:315–323
Spielman RS, Weinshilboum RM (1981) Genetics of red cell COMT activity: analysis of thermal stability and family data. Am J Med Genet 10:279–290
Weinshilboum RM, Raymond FA (1977) Inheritance of low erythrocyte catechol-O-methyltransferase activity in man. Am J Med Genet 29:125–135
White HL, Wu JC (1975) Properties of catechol-O-methyltransferase from brain and liver of rat and human. Biochem J 145:135–143
Wilson AF, Elston RC, Siervogel RM, Weinshilboum R, Ward LJ (1984) Linkage relationships between a major gene for catechol-O-methyltransferase activity and 25 polymorphic marker systems. Am J Med Genet 19:525–532
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Brahe, C., Bannetta, P., Khan, P.M. et al. Assignment of the catechol-O-methyltransferase gene to human chromosome 22 in somatic cell hybrids. Hum Genet 74, 230–234 (1986). https://doi.org/10.1007/BF00282539
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00282539