P.E. Polani

Chiasmata, meiotic univalents, and age in relation to aneuploid imbalance in mice.

Chiamata were counted and paired and unpaired configurations at first meiotic division and chromosome errors at second meiotic division were assessed at different ages in males and females of two strains of laboratory mice. In the females a decrease of chiasma frequency and an increase of univalents at first meiotic metaphase (MI) were confirmed. In the males, diakineses had higher chiasma frequencies (in the range of the female MIs) and fewer univalents than the MIs had. In these male cells there was no decrease of chiasmata or increase of autosomal univalents with age, and there were some interstrain differences. In the older females there was no parallelism between the frequencies of univalents at MI and the chromosome errors that could be identified at second meiotic division; these were fewer than might be expected on the assumption that all the univalents were true univalents. The relevance of this finding to the question of the nature of most of the univalents observed at first meiotic division in aged female mice is discussed.

Cytogenetics of Down’s Syndrome (Mongolism) I. Data on a Consecutive Series of Patients Referred for Genetic Counselling and Diagnosis

The chromosome findings in a series of 173 Down’s syndrome or presumptive Down’s syndrome index patients, and a further 3 5 pairs of parents of Down’s syndrome index cases, are given. One hundred and forty-four index cases had primary G21 trisomy; six were interchange trisomics, six were mosaics, and one was a chromatin positive male with XXY sex chromosomes and primary G21 trisomy. Sixteen index patients whose diagnosis could not be clinically confirmed, were found to have normal chromosomes. The 35 pairs of parents all had normal chromosomes. In seven families (three index patients with primary G21 trisomy, two with normal chromosomes and two index patients not studied) minor morphological chromosome anomalies were observed. The relevance of this data to the causal association of Down’s syndrome and G21 trisomy, the frequency of mosaicism, double trisomy and association with other chromosome anomalies, is discussed.

Cytogenetics of Down’s Syndrome (Mongolism) III. Frequency of Interchange Trisomics and Mutation Rate of Chromosome Interchanges

An attempt is made to obtain an estimate of the frequency of interchange trisomic Down’s syndrome within the general population. This estimate is used to calculate the interchange mutation rate (τ) involving chromosome 21 and resulting in the formation of interchange trisomics. Inadequacies and shortcomings of the data used, the assumptions required and the method employed are discussed. A maximum estimate of 2.71 × 10–5 (1 in 37,000) and a minimum of 2.07 × 10–5 (1 in 48,000) interchanges per chromosome 21, per gamete, per generation, resulting in the formation of interchange trisomics is obtained.

Mouse germ cells and LSD-25

Acute and chronic studies of male and female meiosis in an Imperial-Chemical-Industries-derived strain of mice were carried out with LSD-25. Over a wide range of doses claimed to be effective in terat

FACTORS IN THE ÆTIOLOGY OF ATRIAL SEPTAL DEFECT

The relative importance of heredity and environment in causing malformation of the heart is still uncertain. We hoped that details about the families of our patients might provide some evidence to help in this problem. After a preliminary enquiry about the families of 384 patients, most of whom had Fallots tetralogy (Polani and Campbell, 1955), we thought it would be more useful to make our enquiries in more homogeneous groups. So far, we have covered 261 patients with persistent ductus arteriosus (Polani and Campbell, 1960) and 151 patients with coarctation of the aorta (Campbell and Polani, 1961). In this paper we are applying the same method to the families of 170 patients with atrial septal defect. We are grateful to Dr. Evan Bedford for sending out our questionnaires to about 100 consecutive patients he had seen at the Middlesex Hospital: the 94 of these who replied (Cases 1-94) and 76 of our own patients (101-176) make up this series. We think that the diagnosis is certain in practically all these, and that the defect was of the ostium secundum type in all but three. In those seen at the Middlesex, it was confirmed by cardiac catheterization or operation in all, and generally by both. In the Guys patients it was confirmed by catheterization, necropsy, or operation in all but five, in whom there seemed no doubt about the clinical diagnosis. Several had some pulmonary hypertension, but with A.S.D. this is generally a secondary result of the defect: in seven it was severe enough to have lessened the left-to-right shunt and produced a right-to-left shunt as well.

AMNIOTIC FLUID ACETYLCHOLINESTERASE AND PRENATAL DIAGNOSIS

Raised specific acetylcholinesterase (AChE) activity in amniotic fluid was consistently found to be associated with fetal intrauterine death and neural tube defects, but in just under half of the samples from pregnancies with spina bifida, the increase was marginal. Elevated AChE levels were occasionally found in fluid samples contaminated by maternal blood, and in nearly half of the samples which were a brown or yellow‐brown colour but where there was a normal fetus. Nine fluids, five of which were contaminated with fetal blood, had a false positive result on alpha‐fetoprotein (AFP) assay (elevated AFP levels and a normal fetus), but showed normal AChE activities. It is suggested that AChE estimation might be useful in prenatal diagnosis as a second test for those fluids which have an elevated AFP level.

Transplantation of allogeneic haemopoietic tissue in adult anaemic mice of the w series using antilymphocytic serum.

Abstract Mice which possess a genetically determined macrocytic anaemia were treated with antilymphocytic serum (A.L.S.) and allogeneic haemopoietic cells. Studies on haemoglobin and chromosome markers showed that, in many animals, implantation and proliferation of this foreign tissue ensued. In mice which had received the A.L.S. for only 7 days before the haemopoietic graft the blood picture became normal, and has remained so for 190 days.

THYROID FUNCTION IN TURNER'S SYNDROME AND ALLIED CONDITIONS

Abstract A significant difference in the response to thyroid-stimulating hormone has been demonstrated in two groups of patients with Turners syndrome; patients with thyroid antibodies had a significantly lower response than those without antibodies. The study suggests that these patients have a low thyroid reserve, and in this respect behave like other patients with chronic focal thyroiditis or Hashimotos disease.

GESTATIONAL AGE AT TERMINATION OF PREGNANCY ON MEDICAL INDICATIONS

our experience as a regional genetics center could be of interest to those concerned with the gestational age at the termination of pregnancies for medical reasons. Here there are 4 sets of indications for termination--neural tube defects, unbalanced chromosome disorders, serious and untreatable X-linked disorders, and grave and incurable inborn errors of metabolism. Most determinations for neural tube defects are performed earlier than those for chromosome abnormalities because the alpha fetoproteins assay is done directly on the fluid, while tissue culture and cytology are lengthy procedures. Specific biochemical errors can be quickly identified in those cases where tests can be done directly on the fluid or be based on modest numbers of amniotic cells, but when the specific tests require a large number of cultured cells, a long time lag may be involved. The figures show not what happens under theoretically ideal circumstances, but the real life pattern which emerges in the face of such variables as womans booking habits, amniocentesis failure, culture failure, and the need for repeat amniocentesis.