A single highly-polymorphic autosomal gene locus PUM codes for a family of mucin-type glycoproteins, separable by SDS-gel electrophoresis, which we first identified in human urine. The locus also codes for glycoproteins which are abundant in several other normal epithelial tissues and body fluids, including milk, and in tumours of epithelial origin. These mucin-type glycoproteins seem to be very immunogenic in rodents and, in a search for epithelial specific or tumour-associated antigens, a large number of related antibodies have been isolated which bind to the PUM-coded mucins. Many of the antibodies show a pronounced tumour specificity on immunohistology and are being used widely in cancer diagnosis in vitro and in vivo and even in cancer therapy. To investigate the expression of these antigens in normal and malignant cells complementary DNA coding for the mammary mucin has been isolated. Here we present evidence obtained using this cDNA that the PUM locus is a hypervariable 'minisatellite' region of human DNA similar to those described by several groups, but which is novel in that it is transcribed and translated, and that the same polymorphism is demonstrable in the expressed gene product.

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.

A preliminary analysis of twins or triplets with heart defects, ascertained in five centres, confirms earlier suggestions that monozygotic (MZ) twins are over represented among twins with heart defects, even after excluding persistent ductus arteriosus and conjoined twins. An MZ twin individual has a risk of cardiovascular malformation approximately twice that of DZ twins and singletons. It is suggested that the twinning process itself affects one of the pair. Disturbance of laterality (‘mirror imaging’) is probably a more important mechanism than twin-twin transfusion. Inappropriate use of the twin method in the past has caused the importance of genetic factors in the etiology of congenital heart defects to be underestimated. Neverthless, twins do provide a useful illustration of the likely importance of epigenetic factors in heart development.

SUMMARYHuman 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.Studies on the children of a first cousin marriage led to the identification of a sixth variant phenotype, Dia 2, which is believed to represent the homozygous genotype Dia2Dia2.Individually all of the variants were rare, although collectively the frequency of NADH diaphorase variants was about one in a hundred in European, Indian and Negro population samples. More than half the total number of variants observed were phenotype Dia 2‐1 or Dia 4‐1.The rare Dia6 allele probably determines a low activity form of NADH diaphorase.There was no evidence of linkage between the NADH diaphorase locus and several blood group and other autosomal gene loci.

Data with regard to the proportion of congenital malformations found at birth are presented from a survey of 657 pairs of twins of known zygosity and placentation delivered in Aberdeen and Northeast Scotland between 1968 and 1979. There was an excess of malformed individuals from monozygotic (MZ) pairs, but this did not reach statistical significance. The possible effect of monochorionic placentation in the causation of malformations in MZ twins in general is discussed. It seems that this type of placentation may be of less causative importance than has been previously suggested.