MRC Human Research Articles

The genetic determination of fumarase isozymes in human tissues

(1) A method for the starch gel electrophoresis of human fumarase has been devised which resolves two groups of isozymes: one group (FHM) is associated with the mitochondria, the other (FHS) is cytosolic. (2) Tissue to tissue variation in the complexity of the isozyme patterns and the examination of red cells fractionated according to their age by density gradient centrifugation suggest that the least anodal isozymes of the FHS group and ofthe FHM group are modified in vivo with the generation of several secondary isozymes. (3) Red cells, which display only FHS isozymes, were screened from 776 European and 100 Nigerian individuals and a single electrophoretic variant (phenotype FH 2-1) was identified in a middle-aged male from England. The same variant was identified in a paternal aunt and the data suggest that the variant repressents heterozygosity for the common (FH1) allele and a rare variant (FH2) allele at an autosomal locus. (4) Fibroblasts and white cells from the FH 2-1 individual showed variation in the FHM and FHS isozymes indicating that the mitochondrial and the soluble forms of fumarase are determined at the same structural locus.

Chromosome assignment of some human enzyme loci: mitochondrial malate dehydrogenase to 7, mannosephosphate isomerase and pyruvate kinase to 15 and probably, esterase D to 13.

Eleven independent man-mouse hybrids and 40 subclones from four to them were analysed for up to 42 enzyme markers. Nine subclones from three hybrid lines were fully karyotyped. The data presented suggest that the gene for the human enzyme MOR-M can be assigned to chromosome 7, whilst those for MPI and PK-3 are on chromosome 15. The use of a small number of well-characterized hybrids for gene assigments is discussed as well as the significance of some known human linkage relationships.