G. Corney

Genetically determined electrophoretic variants of human red cell NADH diaphorase.

Human red cell NADH diaphorase isozyme patterns have been examined in blood samples from 2783 unrelated individuals by starch gel electrophoresis. Most people exhibit a single banded isozyme pattern, designated phenotype Dia 1. Twenty‐nine people with variant isozyme patterns were encountered. Five different phenotypes (Dia 2‐1, 3‐1, 4‐1, 5‐1 and 6‐1) were identified, which from family studies appear to represent heterozygous combinations of one or other of a series of rare alleles (Dia2, Dia3, Dia4, Dia5 and Dia6) with a common allele (Dia1) at an autosomal locus.

A genetic polymorphism of a human urinary mucin

We report here a novel genetically determined polymorphism of a human urinary mucin which is demonstrable by the separation technique of SDS polyacrylamide gel electrophoresis, followed by detection with radio‐iodinated lectins. The mucins are demonstrable using various lectins but the polymorphism is most easily recognized using peanut agglutinin and we therefore propose to designate this new genetic locus PUM (peanut‐reactive urinary mucin). Four common alleles have been identified and an autosomal codominant mode of inheritance has been found in the families studied so far.

Acid α-glucosidase: A new polymorphism in man demonstrable by ‘affinity’ electrophoresis

1. A new polymorphism of the enzyme acid alpha-glucosidase is described. The three phenotypes, 1, 2-1 and 2, appear to be determined by two alleles alpha-GLU1 and alpha-GLU2 at an autosomal locus. The allele frequencies in Europeans are approximately alpha-GLU1 = 0-97 and alpha-GLU2 = 0-03. 2. The polymorphism is not detectable after electrophoresis on other support media (cellogel and agarose) and evidence is presented that the separation is effected by a difference in binding of the isozyme products of the two alleles to the support medium starch, which contains alpha-1-4 and alpha-1-6 linked glucose units. We have called this type of separation affinity electrophoresis. 3. No difference in the kinetic properties of the two enzymes could be demonstrated using 4-methyl umbelliferyl alpha-D-glucopyranoside and maltose as substrates or maltose and turanose as inhibitors, but it is possible that differences might exist when macromolecular substrates are used. 4. One individual with the rare homozygous genotype has been found. There is at present no indication that this genotype is associated with a pathological condition.

The genetics of peptidase C in man.

Several distinct peptidases, which may be differentiated by their electrophoretic characteristics, their pattern of substrate specificity and their molecular size, have been demonstrated in human cells (Lewis & Harris, 1967, 1969a; Rapley, Lewis & Harris, 1971). They are referred t o as peptidases A, B, C, D, E, F and S and are thought to be determined by separate gene loci. Genetically determined variants of Pep A, B and D in European, Indian and Negro populations and in Australian aborigines have been described (Lewis & Harris, 1967; Lewis, Corney & Harris, 1968; Lewis & Harris, 1969b; Blake et al. 1970). Genetic variation in Peptidase C (Pep C) has until now only been reported in a group of Babinga pygmies (Santachiara Benerecetti, 1970). She found 5 examples out of 261 random blood samples in which an additional band of Pep C activity appeared, with a lower mobility than the usual Pep C band, and two examples in which the normal band was entirely replaced by the slow band. She also found 11 examples of Pep C absence although Pep A activity remained. On the basis of this and limited family studies she postulated three autosomal alleles, Pep C1, Pep C2 and Pep CO, the product of Pep Co being undetectable electrophoretically. We present here evidence for genetic variation of Pep C in European, Indian and Negro populations, and discuss the relationship of the variants seen with those described by Benerecetti.

Differences between the N-acetyl hexosaminidase isozymes in serum and tissues

There are two main isoenzymes of human N-acetyl P-D-hexosaminidase (NAGA-A and -B), which are separable by starch-gel electrophoresis, isoelectric focusing (A with isoelectric point at about pH 5 , B with isoelectric point at about pH 7) and ion-exchange chromatography (Robinson & Stirling 1968; Okada & O’Brien 1969; Sandhoff, 1969). The isozymes differ in stability but resemble each other closely in many other properties. One of them, the more thermolabile NAGA-A, has been shown to be deficient in tissues and serum of patients with Tay-Sachs disease (Okada & O’Brien, 1969; Sandhoff, 1969; Hultberg, 1969). In some patients with a similar clinical disorder both isozymes are absent (Sandhoff, Andreae & Jatzkewitz, 1968 ; Young et al. 1970; O’Brien 1972; Juif et al. 1973; Vidailhet et al. 1973). This condition is now often referred to as Sandhoff’s disease. It is still unclear after nearly 5 years in what way the A and B isozymes are related and how many genes are involved in their determination (Tateson & Bain, 1971; Robinson & Carroll, 1972; Srivastava & Beutler, 1973; Robinson, Carroll & Stirling, 1973). It would seem highly unlikely that two independent rare recessives occur together in patients with the deficiency of both isozymes, and although a small deletion of two closely linked loci cannot be excluded it is perhaps more probable that the isozymes contain common polypeptides. The isozymes may be multimeric, and there may be two or more distinct subunits determined by separate loci. The two isozymes may differ from one another in the particular combination of subunits they possess. There are many precedents in human biochemical genetics for this general concept (Hopkinson & Harris, 1971). The presence in homozygous form of a gene causing an abnormality in a common subunit could account for the deficiency of both isozymes. A gene causing an abnormality in a polypeptide subunit present only in the A isozyme could account for NAGA-A deficiency. An alternative possibility is that the A and B isozymes represent the same gene product and that one isozyme is a modification of the other. The defect in Tay-Sachs disease would on this hypothesis be an abnormality in the primary gene product which prevents the modification, or a mutation of a possible conversion enzyme. Under certain conditions partially purified NAGA-A from human tissues can undergo some conversion to a slower mobility form that resembles B (Robinson & Stirling, 1968; Dance, Price & Robinson, 1970; Srivastava & Beutler, 1973), though it is not clear whether this form is identical to NAGA-B. Robinson & Stirling (1968) claimed that the conversion of spleen NAGA-A could be enhanced by the enzyme neuraminidase and suggested at that time that the A form contains a number of sialic acid residues and might be a glycoprotein which differs from the B form only in its carbohydrate portion. This in turn had led to the suggestion that NAGA-B

Pep A5–1 and Pep A6–1: two new variants of peptidase A with features of special interest

1. Two rare peptidase A phenotypes, Pep A 5–1 and Pep A 6–1, have been found in the course of population surveys of red cell peptidases.

Studies on the quantitative variation of human red cell peptidase A activity

1. A new method for the assay of peptidase A activity in human red cells and leucocytes is described.

Twin zygosity and placentation

The relationship between placentation and zygosity is discussed in an unselected series of 326 twin births. Zygosity determinations were based on sex, red‐cell antigens ABO, MNSs, Rh, Lua, K and Fa, the red‐cell enzymes Ac. P., 6‐PGD, PGM1 and AK and placental alkaline phosphatase. The results indicate that, whereas dizygotic twins are always dichorionic, between 15% and 20% of monozygotic twins may also be dichorionic. Tables are given which allow information on the enzyme phenotypes to be utilized in estimating the probability of dizygosity in the case of twin pairs alike for all characters tested, where the types of the parents are unknown.

The effect of zygosity on the birth weight of twins

Birth weight has been analysed in a series of 528 unselected, newborn twins pairs of known zygosity, in relation to sex, placentation, duration of gestation, maternal age and parity. Monozygotic twins weigh less than dizygotic twins, even when the named variables are allowed for. Possible reasons for this are discussed.

Anomalous cellular proliferation in vitro associated with Huntington's disease

SummaryDetailed growth analyses of cultured skin fibroblasts from two patients with Huntingtons Disease (HD) were compared with those from controls matched for age and sex. In contrast to control cells, HD fibroblasts plated more efficiently at the low seeding densities used. Subsequent exponential growth of HD cultures was more stable towards routine trypsinisation than that of controls. However, the most striking feature of HD cultures was their ability to grow to significantly higher cell saturation densities. Experiments with trypsinised and untrypsinised cultures imply an inherent alteration in the HD cell membrane.