Molecular genetics in clinical practice: evolution of a DNA diagnostic service.

The development of a molecular genetics diagnostic service over a three year period was studied in a National Health Service region with a population of three million. Starting from a time when few diagnostic applications were possible, the number of disorders and the overall demand had grown rapidly. Conditions for which molecular genetic diagnosis had been provided included Duchenne and Becker muscular dystrophy, myotonic dystrophy, Huntington's disease, and cystic fibrosis.

Advanced laryngeal cancer: a management perspective.

A retrospective study of 197 T3 and T4 squamous cell carcinomas of the larynx presenting between 1969 and 1978 has been undertaken. These patients have in the main been treated by primary radiotherapy with back-up salvage surgery. The aim of the study was to examine survival, and to try to identify reasons for failure of control.

Is birth weight determined genetically?

Birthweight correlations were analysed among 505 intergenerational pairs of first births to women aged 18-25 identified from a large obstetric data bank. After standardisation for fetal sex, maternal height, gestational age, and proteinuric pre-eclampsia residual correlations of between 0.1402 and 0.

Exclusion testing for Huntington's disease in pregnancy with a closely linked DNA marker.

55 couples where one partner was at 50% risk of Huntington's disease (HD) were investigated with a DNA probe closely linked to HD, with a view to exclusion testing in a future pregnancy. In 3 of 9 pregnancies so far, HD was excluded in the absence of recombination. In 3 the risk was raised to around 50%, and in 2 exclusion tests were uninformative.

Application of a closely linked polymorphism of restriction fragment length to counselling and prenatal testing in families with myotonic dystrophy.

The close genetic linkage between the loci for apolipoprotein CII (ApoC2) and myotonic dystrophy makes ApoC2 the closest fully validated marker for prediction of myotonic dystrophy. Application to genetic counselling and presymptomatic and prenatal prediction is reported in seven families with myotonic dystrophy, including one case in which the disorder was excluded prenatally. Only one of the families did not have members with ApoC2 genotypes that allowed prediction, but careful clinical study of older family members was found to be an important factor.

Linkage relationships of the insulin receptor gene with the complement component 3, LDL receptor, apolipoprotein C2 and myotonic dystrophy loci on chromosome 19.

Myotonic dystrophy is associated with disturbances in the insulin response, possibly due to an abnormality of the insulin receptor. Both the myotonic dystrophy (DM) and insulin receptor (INSR) genes are on chromosome 19. Using a cloned gene probe for INSR, we have studied its linkage relationships with the DM locus and other chromosome 19 markers.

Regional localisations and linkage relationships of seven RFLPs and myotonic dystrophy on chromosome 19.

We have studied the genetic linkage relationships of seven DNA polymorphisms on chromosome 19, with each other and with the myotonic dystrophy locus. The DNA sequences were localised to various regions of the chromosome using translocations in somatic cell hybrids. These results provide the basis for a linkage map of most of chromosome 19, and suggest that the myotonic dystrophy locus is close to the centromere.

Linkage analysis of peripheral neurofibromatosis (Von Recklinghausen disease) and chromosome 19 markers linked to myotonic dystrophy.

Three chromosome 19 markers known to be linked to myotonic dystrophy have been studied in nine families with peripheral neurofibromatosis (Von Recklinghausen's disease). Clear evidence against linkage has been found for all three markers, excluding the peripheral neurofibromatosis gene from the myotonic dystrophy region of chromosome 19. Previous reports of co-inheritance of the two disorders in families cannot therefore be explained on the basis of close genetic linkage between the loci.

Gene mapping and chromosome 19.

Chromosome 19 is currently the most fully mapped of the smaller chromosomes, with about 40 loci assigned to it (HGM8). Major inherited disorders on this chromosome include myotonic dystrophy and familial hypercholesterolaemia. Other loci include five blood groups, a cluster of apolipoprotein genes, and the receptors for insulin and polio virus.

Mapping genetic markers on human chromosome 19 using subchromosomal fragments in somatic cell hybrids.

A series of mouse-human somatic cell hybrid lines (WILF) were derived from a hybrid that was originally thought to have chromosome 19 as its only human chromosome. In situ hybridization has been used to assess the amount of human material present in the different lines. All appear to contain different numbers of human chromosome fragments.

Evidence against linkage of von Recklinghausen neurofibromatosis and chromosome 19 markers.

In this paper we report the study of the segregation of three chromosome 19 markers known to be linked to myotonic dystrophy in nine families with von Recklinghausen neurofibromatosis. Clear evidence against linkage was found for all three markers excluding the von Recklinghausen neurofibromatosis gene from the myotonic dystrophy region of chromosome 19.

The apolipoprotein CII gene: subchromosomal localisation and linkage to the myotonic dystrophy locus.

The human apolipoprotein CII gene probe detects a restriction fragment length polymorphism located on chromosome 19. We have investigated the linkage of this polymorphism to the myotonic dystrophy locus in families. The two loci are closely linked with a maximum Lod score of 7.

In vitro studies on calcium activated phosphatidylinositol phosphodiesterase of erythrocyte ghosts from normal individuals and those with myotonic muscular dystrophy.

Myotonic muscular dystrophy is an inherited disorder affecting many organs, though the underlying biochemical defect is unknown. A recent publication [1] suggested that the metabolic lesion may be associated with defective phospholipid metabolism. These workers observed impaired calcium-stimulated phosphatidic acid accumulation in red cell ghosts from individuals with myotonic dystrophy compared with normal controls.

Some studies of maternal and infant lead exposure in Glasgow.

In two studies in the city of Glasgow, 236 mothers and their newly born infants and 117 mothers and their 6-weeks old children's environmental lead exposure were examined. In both studies blood lead concentrations were found to correlate significantly with the cube root of the domestic water lead concentrations. In the first study, multiple regression analyses of maternal blood lead and cord blood lead concentrations on other variables showed a significant negative correlation with gestational age.

Methods for the study of lung metabolism.

The recognition of the non-respiratory functions of the lung has led to an increased interest in pulmonary metabolism. The practical methods used to study metabolism in other tissues have all been applied to the investigation of lung metabolism. Methods fall into two groups: those used in vivo and those used in vitro after disrupting the organ or isolating it from other tissues and perfusing its circulation.