Taggart R T, Mohandas T K, Bell G I
Somat Cell Mol Genet. 1987 Mar;13(2):167-72. doi: 10.1007/BF01534696.
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 X 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 PGA genes 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 PGA genes, respectively. This unusual polymorphism of genomic DNA encoding very similar proteins probably reflects recent evolution by gene duplication.
胃蛋白酶原（PGA）是胃中主要的酸性蛋白酶胃蛋白酶的无活性前体。这些蛋白质的高度多态性变异已在多个群体中得到证实，对从信息丰富的胃蛋白酶原表型获得的DNA限制性片段模式进行比较表明，这种多态性是由包含不同数量胃蛋白酶原基因的染色体单倍型导致的。为了分离出三种最常见的PGA单倍型（A、B和C），并明确证明它们与观察到的蛋白质异质性的关系，我们从对PGA和INS（胰岛素）杂合的个体构建了小鼠×人类体细胞杂种。在此，我们描述了对杂交细胞系的分析，这些细胞系分离出了含有PGA基因的人类染色体，从而实现了对11号染色体上决定相应杂合表型的不同单倍型的准性鉴别。这些研究表明，A、B和C单倍型分别包含三个、两个和一个PGA基因。编码非常相似蛋白质的基因组DNA的这种不寻常多态性可能反映了通过基因复制的近期进化。
