Summary
A cloned human cDNA for cholinesterase (ChE) was used as a probe for in situ hybridization to spread lymphocyte chromosomes to map the structural human CHE genes to distinct chromosomal regions. The recent genetic linkage assignment of the CHE1 locus of the CHE gene to chromosome 3q was confirmed and further refined to 3q21-q26, close to the genes coding for transferrin (TF) and transferrin receptor (TFRC). The CHE1 allele localizes to a 3q region that is commonly mutated and then associated with abnormal megakaryocyte proliferation in acute myelodysplastic anomalies. In view of earlier findings that ChE inhibitors induce megakaryocytopoiesis in culture, this localization may indicate that ChEs are involved in regulating the differentiation of megakaryocytes. A second site for ChEcDNA hybridization was found on chromosome 16q11-q23, demonstrating that the CHE2 locus of the cholinesterase gene, which directs the production of the common C5 variant of serum ChE, also codes for a structural subunit of the enzyme and is localized on the same chromosome with the haptoglobin (HP) gene, both genes being found on the long arm of chromosome 16. The finding of two sites for ChEcDNA hybridization suggests that the two loci coding for human ChEs may include nonidentical sequences responsible for the biochemical differences between ChE variants.
Similar content being viewed by others
References
Arias S, Rolo M, Gonzalez N (1985) Gene dosage effect present in trisomy 3q25.2-qter for serum cholinesterase (CHE1) and absent for transferrin (TF) and ceruloplasmin (CP). Cytogenet Cell Genet 40:571
Bernstein R, Pinto MR, Behr A, Mendelow B (1982) Chromosome 3 abnormalities in acute nonlymphocytic leukemia (ANLL) with abnormal thrombopoiesis: report of three patients with a “new” inversion anomaly and a further case of homologous translocation. Blood 60:613–617
Burstein SA, Adamson JW, Waker LA (1980) Megakaryocytopoiesis in culture: modulation by cholinergic mechanisms. J Cell Physiol 103:201–208
Carbonell F, Hoelzer D, Thiel E, Bartl R (1982) Ph1 positive CML associated with megakaryocytic hyperplasia and thromobocytemia and an abnormality of chromosome no. 3. Cancer Genet Cytogenet 6:153–161
Caspersson T, Zech L, Modest EJ, Foley EE, Wagh U, Simonsson E (1985) DNA binding fluorochromes for the study of the organization of the metaphase nucleus. Exp Cell Res 58:141–152
Coates PM, Simpson NE (1972) Genetic variation in human erythrocyte acetylcholinesterase. Science 175:1466–1467
Drews U (1975) Cholinesterase in embryonic development. Prog Histochem Cytochem 7:1–52
Huerre C, Uzan G, Greschik KH, Weil D, Levin M, Hors-Cayla MC, Boue J, Kahn A, Junien C (1984) The structural gene for transferrin (TF) maps to 3q21-3qter. Ann Génét (Paris) 27:5–10
Kidd KK, Gusella (1985) Report of the committee on the genetic constitution of chromosomes 3 and 4. J Cytogenet Cell Genet 40:107–127
Layer PG (1983) Comparative localization of acetylcholinesterase and pseudocholinesterase during morphogenesis of the chicken brain. Proc Natl Acad Sci USA 80:6413–6417
Lockridge O (1984) Amino acid composition and sequence of human serum cholinesterase: a progress report. In: Brzin M, Barnard EA, Sket D (eds) Cholinesterases, fundamental and applied aspects. de Gruyter, Berlin, pp 5–12
Lovrien EW, Magenis RE, Rivas ML, Lamvik N, Rowe S, Wood J, Hemmerling J (1978) Serum cholinesterase ChE2 linkage analysis: possible evidence for localization to chromosome 16. Cytogenet Cell Genet 22:324–326
Massoulie JM, Bon S (1982) The molecular forms of cholinesterase and acetylcholinesterase in vertebrates. Am Rev Neurosci 5:57–106
Mattei MG, Philip N, Passage E, Moisan JP, Mandel JL, Mattei JE (1985) The gene encoding for the major brain proteolipid (PLP) maps on the q22 band of the human x chromosome. Hum Genet 69:268–271
Paulus JP, Maigen J, Keyhani E (1981) Mouse megakaryocytes secrete acetylcholinesterase. Blood 58:1100–1106
Pintado T, Ferro MT, San Roman C, Mayayo M, Larana JG (1985) Clinical correlations of the 3q21;q26 cytogenetic anomaly; a leukemic or myelodysplastic syndrome with preserved or increased platelet production and lack of response to cytotoxic drug therapy. Cancer 55:535–541
Prody C, Zevin-Sonkin D, Gnatt A, Koch R, Zisling R, Goldberg O, Soreq H (1986) Use of synthetic oligodeoxynucleotide probes for the isolation of a human cholinesterase cDNA clone. J Neurosci Res 16:25–36
Prody C, Zevin-Sonkin D, Gnatt A, Goldberg O, Soreq H (1987) Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues. Proc Natl Acad Sci USA 84:3555–3559
Rabin M, Fries R, Singer D, Ruddle FH (1985) Assignment of the Porcine major histocompatibility complex to chromosome 7 by in situ hybridization. Cytogenet Cell Genet 39:206–209
Razon N, Soreq H, Roth E, Bartal A, Silman I (1984) Characterization of levels and forms of cholinesterases in human primary brain tumors. Exp Neurol 84:681–695
Silver A (1974) The biology of cholinesterases. North-Holland, Amsterdam
Simmers RN, Stupans I, Sutherland GR (1986) Localization of the human haptoglobin genes distal to the fragile site at 16q22 using in situ hybridization. Cytogenet Cell Genet 41:38–41
Simpson NE (1966) Factors influencing cholinesterase activity in a Brazilian population. Am J Hum Genet 18:243–252
Soreq H, Zevin-Sonkin D, Goldberg O, Prody C (1987) Molecular biology approach to the expression of mammalian cholinesterase. In: Heinemann S, Patrick J (eds) Current topics in neurobiology: molecular neurobiology. Plenum Press, New York, pp 191–224
Sparkes RS, Field LL, Sparkes MC, Crist M, Spence MA, James K, Garry PJ (1984) Genetic linkage studies of transferrin, pseudocholinesterase and chromosome 1 loci. Hum Hered 34:96–100
Sweet DL, Golomb HM, Rowley JD, Vardiman JM (1979) Acute myelogenous leukemia and thrombocytemia associated with an abnormality of chromosome no. 3. Cancer Genet Cytogenet 1:33–37
Whittaker M (1980) Plasma cholinesterase and the anaesthetist. Anaesthesia 35:174–197
Yang F, Lum JB, McGill JR, Moore CM, Naylor SL, Van-Bragt PH, Baldwin WD, Bawman BH (1984) Human transferrin: cDNA characterization and chromosomal localization. Proc Natl Acad Sci USA 81:2752–2757
Zakut H, Matzkel A, Schejter E, Avni A, Soreq H (1985) Polymorphism of acetylcholinesterase in discrete regions of the developing human fetal brain. J Neurochem 45:382–389
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Soreq, H., Zamir, R., Zevin-Sonkin, D. et al. Human cholinesterase genes localized by hybridization to chromosomes 3 and 16. Hum Genet 77, 325–328 (1987). https://doi.org/10.1007/BF00291419
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00291419