A genetic characterization of the human diaphorase-4 deficiency

Analyses of DIA4 activity in cultured cells from a random population, a small family and human/rodent somatic cell hybrids support the view that the quantitative polymorphism of human DIA4 can be attributed to the segregation of a 'low activity' allele. (1) In a series of lymphoblastoid cell lines from 52 unrelated individuals, three lines were found which did not exhibit DIA4 after electrophoresis and showed low levels of NADPH diaphorase activity. The frequency (6%) of the DIA4 'absent' phenotype is close to that (4%) determined previously by analysis of post-mortem tissue. (2) Cultured fibroblasts from a small family in which the DIA 4 low-activity allele was apparently segregating were analysed. The NADPH diaphorase activity of the propositus (DIA4 'absent' phenotype) was very low (less than 6% of normal). He also exhibited very weak DIA4 isozymes of unusual electrophoretic mobility. The activity of both parents and sib was about half the normal level, suggesting that these individuals are heterozygous for the low-activity allele. (3) Analysis of a series of independent human/hamster hybrid clones, made using a human parent heterozygous for phosphoglycolate phosphatase (PGP) and DIA4, suggested that in this particular individual the DIA 4 low-activity allele segregates with the PGP 2 allele. However, there were 2 hybrids amongst a total of 16 which gave discordant results and these are to be the subject of further analysis by subcloning.