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Parasexual analysis of human pepsinogen molecular heterogeneity

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Somatic Cell and Molecular Genetics

Abstract

Pepsinogens (PGA) are the inactive precursors of pepsin, the major acid protease found in the stomach. Highly polymorphic variation of these proteins has been demonstrated in several populations, and comparison of the DNA restriction fragment patterns obtained from informative pepsinogen phenotypes suggest that the polymorphism results from chromosomal haplotypes containing variable numbers of pepsinogen genes. In order to isolate the three most common PGA haplotypes (A, B, and C) and to unambiguously demonstrate their relationship to the observed protein heterogeneity, we constructed mouse × human somatic cell hybrids from individuals heterozygous for PGA and INS (insulin). Here, we describe analysis of hybrid cell lines that segregated human chromosomes containing the PGAgenes and thereby provided for the parasexual discrimination of the different haplotypes on chromosome 11 determining the corresponding heterozygous phenotypes. These studies demonstrate that the A, B, and C haplotypes contain three, two, and one PGAgenes, respectively. This unusual polymorphism of genomic DNA encoding very similar proteins probably reflects recent evolution by gene duplication.

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Author notes

  1. R. Thomas Taggart

    Present address: Dept. of Molecular Biology and Genetics, Wayne State University School of Medicine, 3216 Scott Hall, 48201, Detroit, Michigan

Authors and Affiliations

  1. Human Genetics Research (151M), Veterans Administration Medical Center, 91343, Sepulveda, California

    R. Thomas Taggart

  2. Department of Medicine, University of California Los Angeles, 90073, California

    R. Thomas Taggart

  3. Division of Medical Genetics, Harbor General Hospital, University of California Los Angeles, 1000 West Carson Street, 90509, Torrance, California

    T. K. Mohandas

  4. Howard Hughes Medical Institute, University of Chicago, 920 East 58 Street, 60637, Chicago, Illinois

    Graeme I. Bell

Authors
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  2. T. K. Mohandas
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  3. Graeme I. Bell
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Taggart, R.T., Mohandas, T.K. & Bell, G.I. Parasexual analysis of human pepsinogen molecular heterogeneity. Somat Cell Mol Genet 13, 167–172 (1987). https://doi.org/10.1007/BF01534696

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  • DOI: https://doi.org/10.1007/BF01534696

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