Summary
Human pepsinogen (PGA) exhibits extensive polymorphism that can be detected both at the protein and the DNA level. We describe here two restriction fragment length polymorphisms, EcoRI and BglII, which provide for the detection of three of the most common PGA haplotypes (A, B, and C) in the United States population. The relationship of these polymorphisms to each PGA haplotype was determined by analysis of DNA from individuals exhibiting the corresponding protein phenotypes and by analysis of a series of human × mouse somatic cell hybrids containing the individual chromosome 11 homologous from heterozygous individuals exhibiting the AB and AC protein phenotypes. The use of the BglII polymorphism in combination with previously described EcoRI polymorphism provides a very informative marker of 11q13.
References
Bebelman JP, Evers MPJ, Zelle B, Bank R, Pronk JC, Meuwissen SGM, Mager WH, Planta RJ, Eriksson AW, Frants RR (1989) Family and population studies on the human pepsinogen A multigene family. Hum Genet 82:142–146
Evers MPJ, Zelle B, Peeper DS, Mager WH, Planta R, Eriksson AW, Frants RR (1987) Molecular cloning of a pair human pepsinogen A genes which differ by a Glu→Lys mutation in the activation peptide. Hum Genet 77:182–187
Evers MPJ, Zelle B, Bebelman JP, Beusechem V van, Kraakman L, Hoffer MJV, Pronk JC, Mager WH, Planta RJ, Eriksson AW, Frants RR (1989) Nucleotide sequence comparison of five human pepsinogen A (PGA) genes: evolution of the PGA multigene family. Genomics 4:232–239
Feinberg AP, Vogelstein B (1983a) A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13
Feinberg AP, Vogelstein B (1983b) A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Addendum. Anal Biochem 137:266–267
Frants RR, Pronk JC, Pals G, Defize J, Westerveld BD, Meuwissen SGM, Kreuning J, Ericksson AW (1984) Genetics of urinary pepsinogen: a new hypothesis. Hum Genet 65:385–390
Hayano T, Sogawa K, Ichihara Y, Fujii-Kuriyama Y, Takahashi K (1986) Close linkage of human chromosomal pepsinogen A genes. Biochem Biophys Res Commun 38:289–296
Korsnes L, Gedde-Dahl T (1980) Genetics of pepsinogen I. Ann Hum Genet 43:199–212
Nakai H, Byers MG, Shows TB, Taggart RT (1986) Assignment of the pepsinogen gene complex (PGA) to human chromosome 11q13 by in situ hybridization. Cytogenet Cell Genet 43:215–217
Nakamura Y, Larsson C, Julier C, Bystrom C, Skogseid B, Wells S, Oberg K, Carlson M, Taggart T, O'Connell P, Leppert M, Lalouel J-M, Nordenskjold M, White R (1989) Localization of the genetic defect in multiple endocrine neoplasia type 1 within a small region of chromosome 11. Am J Hum Genet 44:751–755
Samloff IM, Townes PL (1970a) Pepsinogens: genetic polymorphism in man. Science 168:144–145
Samloff IM, Townes PL (1970b) Electrophoretic heterogeneity and relationships of pepsinogens in human urine, serum and gastric mucosa. Gastroenterology 58:462–469
Sogawa K, Fujii-Kuriyama Y, Mizukami Y, Ichihara Y, Takahashi K (1983) Primary structure of human pepsinogen gene. J Biol Chem 258:5306–5311
Taggart RT, Samloff IM (1987) Immunochemical, electrophoretic, and genetic heterogeneity of pepsinogen I. Gastroenterology 92:143–150
Taggart RT, Karn RC, Merritt AD, Yu PL, Conneally PM (1979) Urinary pepsinogen isozymes: a highly polymorphic locus in man. Hum Genet: 52:227–238
Taggart RT, Mohandas TK, Shows TB, Bell GI (1985) A gene complex containing variable numbers of pepsinogen genes is located in the centromeric region of human chromosome 11 and determines the high frequency electrophoretic polymorphism. Proc Natl Acad Sci USA 82:6240–6244
Taggart RT, Samloff IM, Raffel LJ, Graham A, Cass C, Petersen GM, Rotter JI, Skolnick MH, Schwartz CE, Bell GI (1986) Relationships between the human pepsinogen DNA and protein polymorphisms. Am J Hum Genet 38:848–854
Taggart RT, Mohandas TK, Bell GI (1987) Parasexual analysis of human pepsinogen molecular heterogeneity. Somat Cell Mol Genet 13:167–172
Taggart RT, Boudi FH, Bell GI (1988) RFLP's for the human pepsinogen A haplotypes (PGA). Nucleic Acids Res 16:9371
Weitkamp LR, Townes PL (1975) Genetics of the urinary pepsinogen isozymes. In: Market CL (ed) Isozymes: genetics and evolution, vol 4. Academic Press, New York London, pp 829–838
Zelle B, Geurts van Kessel A, De Wit J, Evers MPJ, Arwert F, Pronk JC, Mager WH, Planta RJ, Eriksson AW, Frants RR (1985) Assignment of human pepsinogen A locus to the q12-pter region of chromosome 11. Hum Genet 70:337–340
Zelle B, Evers MPJ, Groot PC, Bebelman JP, Mager WH, Planta RJ, Pronk JC, Meuwissen SGM, Hofker MH, Eriksson AW, Frants RR (1988) Genomic structure and evolution of the human pepsinogen A multigene family. Hum Genet 78:79–82
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Boudi, F.H., Lothe, R.A. & Taggart, R.T. Human pepsinogen A (PGA): an informative gene complex located at 11q13. Hum Genet 84, 293–295 (1990). https://doi.org/10.1007/BF00200579
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00200579