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Biomedical subjects

C M Gosden

Publications and source records attributed to C M Gosden.

At least 55 records · Page 3Linked to original sources
PubMed1984

The use of cloned Y chromosome-specific DNA probes for fetal sex determination in first trimester prenatal diagnosis.

Prenatal diagnosis by chorion biopsy in the first trimester of pregnancy has advantages over second trimester amniocentesis because diagnosis can be achieved at 9-12 weeks gestation, reducing prenatal anxiety and avoiding the trauma of late abortion. DNA can be prepared from chorionic villus biopsies in sufficient quantity and purity for use in prenatal diagnosis systems using specific DNA probes hybridised to restriction endonuclease digests. DNA probes derived from the Y chromosome have been used to determine fetal sex. The use of such probes means that the chromosomal sex of the fetus can be identified more quickly than by chromosome preparation and more accurately than by sex chromatin staining, and has the additional advantage that the same DNA preparation can be used for other diagnostic tests. A dot hybridisation method has been successfully used to provide even more rapid results than conventional hybridisation to Southern blots of restriction endonuclease digests. There is a risk that Y chromosome-specific DNA probes for sex determination may be subject to error if the parents have extreme Y chromosome variants such as a small or non-fluorescent Y or a Y autosome chromosome translocation. The precise extent to which such chromosome variants may lead to error has been investigated. Even extreme Y chromosome variants totally lacking fluorescence were identified as male by the cloned probes used. However, Y autosome translocations carried by females could cause error if not identified in the parents. The value of the probes has been confirmed provided that parental chromosomes and DNA are examined in parallel with the chorionic biopsy material.

Cloning, Molecular↗
PubMed1982

Direct vision chorion biopsy and chromosome-specific DNA probes for determination of fetal sex in first-trimester prenatal diagnosis.

Fetal sex was determined prenatally by molecular analysis of DNA from chorionic biopsy specimens taken in the first trimester of pregnancy. Single villi were obtained transcervically under direct vision with ultrasound guidance. The results of restriction endonuclease analysis of Y-chromosome-specific DNA from the biopsy specimens of 13 patients were confirmed in all cases by fetal karyotype analysis of cultures of biopsy specimens taken in parallel and of cultures of the products of conception. Prenatal sex determination by this method takes only 3-4 days and is not subject to the same errors as F-body identification.

Adolescent↗
PubMed1981

Satellite DNA sequences in the human acrocentric chromosomes: information from translocations and heteromorphisms.

Satellite III DNA has been located by in situ hybridization in chromosomes 1, 3--5, 7, 9, 10, 13--18, 20--22, and Y and ribosomal DNA (rDNA) in the acrocentric chromosomes 13--15, 21, and 22. In the acrocentric chromosomes, the satellite DNA is located in the short arm. Here we report comparisons by in situ hybridization of the amount of satellite DNA in Robertsonian translocation and "normal variant" chromosomes with that in their homologs. In almost all dicentric Robertsonian translocations, the amount of satellite DNA is less than that in the normal homologs, but it is rarely completely absent, indicating that satellite DNA is located between the centromere and the nucleolus organizer region (NOR) and that the breakpoints are within the satellite DNA. The amount of satellite DNA shows a range of variation in "normal" chromosomes, and this is still more extreme in "normal variant" chromosomes, those with large short arm (p+ or ph+) generally having more satellite DNA than those with small short arms (p- or ph-). The cytological satellites are heterogeneous in DNA content; some contain satellite DNA, others apparently do not, and the satellite DNA content is not related to the size or intensity of fluorescence of the satellites. The significance of these variations for the putative functions of satellite DNA is discussed.

Centromere↗
PubMed1980

Prenatal diagnosis of epidermolysis bullosa letalis.

The prenatal diagnosis of epidermolysis bullosa letalis was made by electron microscopy of a biopsy specimen of fetal skin taken under direct vision by fetoscopy at 18 weeks' gestation. The diagnosis was confirmed after termination of pregnancy. Abnormalities were found in the number, size, and scanning-electron-microscope appearance of amniotic-fluid cells. These techniques have considerable potential for rapid diagnostic studies in a number of other conditions.

Adult↗
PubMed1979

Satellite DNA loss and nucleolar organiser activity in an individual with a de novo chromosome 13,14 translocation.

The distribution of satellite DNA and nucleolar organiser activity have been studied in a female with a new dicentric translocation chromosome derived from the maternal chromosomes 13 and 14. More than half the satellite DNA (60.5%) was lost in the translocation, together with both the nucleolar organiser regions (NOR'S). However, at least one NOR (chromosome 21) which was inactive in the mother (by the AgI reaction) is active in the subject, and this may be an example of functional compensation. The somatic cells of the mother of the subject, which do not have the translocation, show a high frequency of acrocentric associations, but these do not include any obvious excess of associations involving chromosomes 13 and 14, indicating that the high frequency of association in somatic cells is not in itself a predisposition to Robertsonian translocation in germ line cells. The father's chromosomes 9 both have more satellite DNA in the secondary constriction than normal, but this is not reflected in any obviously larger size of the C-band in this region.

Cell Nucleolus↗
PubMed1978

Central nervous system abnormalities--contrasting patterns in early and late pregnancy.

A total of 509 specimens of spontaneous abortion were studied. Of 364 complete specimens, 15 (4.1%) had central nervous system (CNS) abnormalities. The defects which were seen were anencephaly, spina bifida, iniencephaly, encephalocele and anencephaly combined with complete rachischisis. A high proportion (five out of 15) had the more unusual defects of iniencephaly and encephalocele. All except one had ceased development at less than 12 weeks of gestation. Sex chromatin studies showed that males outnumbered females amount CNS defective fetuses. When the month of conception was calculated for these abnormal pregnancies, summer and winter peaks were detected. Only one of the 15 patients had a family history of neural tube defect (NTD). Histological examination of all small fetuses aborted spontaneously revealed two additional facts. First, in fetuses with a localised external CNS defect, the internal abnormality was more extensive. Second, the CNS was also abnormal in some fetuses with no visible external defect. The proportion of abnormality is much higher than at birth and is also higher than in other surveys of spontaneous abortion. We suggest that screening for serum alphafetoprotein should be undertaken and amniocentesis considered in pregnancies subsequent to an abortion of this type.

Abortion, Spontaneous↗
PubMed1977

The distribution of sequences complementary to human satellite DNAs I, II and IV in the chromosomes of chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla) and orang utan (Pongo pygmaeus).

Human satellite DNAs I, II and IV were transcribed to yield radioactive complementary RNAs (cRNAs). These cRNAs were hybridised to metaphase chromosomes of man, chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla) and orang utan (Pongo pygmaeus). The results of this in situ hybridisation were analysed quantitatively and compared with accepted chromosome homologies based on Giemsa banding patterns. The cRNA to satellite II (cRNAII) did not hybridise to chimpanzee chromosomes, although its hybridisation to chromosomes of gorilla and orang utan yielded more autoradiograph grains than hybridisation to human chromosomes, and cRNAIV hybridised to many chromosomes of gorilla and chimpanzee but was almost entirely restricted to the Y chromosome in orang utan. Most sites of hybridisation were located on homologous chromosomes in all four species, but there were a number of sites which showed no correspondence between satellite DNA location and chromosome banding patterns, and others where a given chromosomal location hybridised with different cRNAs in each species. These results are in contrast to those found for many transcribed DNA sequences, where the same sequence is usually located at homologous chromosome sites in different species, and appear to cast doubt on many proposed models of satellite DNA function.

Animals↗
PubMed1977

Morphology of rapidly adhering amniotic-fluid cells as an aid to the diagnosis of neural-tube defects.

In 20 amniotic-fluid samples taken in the second trimester from pregnancies in which the fetus had a neural-tube defect, the proportion of the total viable cell which adhered to glass surfaces after 20 hours in culture ranged from 9 to 100%. In 92 normal amniotic fluids this proportion was less than 6%. Furthermore, the morphology of the rapidly adhering cells was characteristic in spina bifida (8 cases) and anencephaly (12 cases) and distinct from the epithelioid-like cell seen in normal amniotic fluids, including many which were grossly blood-stained. A sample of amniotic fluid from fetal exomphalos and one from a pregnancy in which the placenta had been repeatedly traversed during amniocentesis had proportions of adherent cells in the pathological range, but the morphologies were very different from those seen in neural-tube defects. It is suggested that the techniques described here will be useful adjuncts to amniotic-fluid alpha-fetoprotein determination in the early diagnosis of fetal abnormality, particularly in blood-stained samples.

Adhesiveness↗
PubMed1976

Clinical details, cytogenic studies,and cellular physiology of a 69, XXX fetus, with comments on the biological effect of triploidy in man.

A triploid fetus, 69, XXX, aborted spontaneously at 26 weeks' gestation. It had multiple abnormalities including syndactyly of the hands and feet single palmar creases, hypoplasia of the adrenals and ovaries, hypertrophy of thigh muscles, and abnormalities of the brain. The placenta was large and showed hydatidiform degeneration. The pregnancy had been complicated by acute dyspnoea, pre-eclampsia, and postpartum haemorrhage. Detailed cytogenetic studies, using banding and fluorescence techniques, were performed on fetus and parents. Meiotic studies were made on the fetal ovaries. Muscle cell differentiation and electrophysiological relationships of cultured skin fibriblasts were examined in an attempt to study the way in which the extra haploid set of chromosomes exerts its effect on the phenotype. The antenatal diagnosis of late triploidy is discussed. The finding that 25 per cent of late triploids have spina bifida is further evidence that meningomyelocele has a genetic component and strongly suggests that this results from chromosomal imbalance or a regulatory gene disturbance.

Abnormalities, Multiple↗
PubMedDate not supplied

Prenatal diagnosis of fragile X syndrome by placental (chorionic villi) biopsy culture.

Second trimester ultrasound-guided fetal blood sampling and placental biopsy were performed on 10 pregnancies at risk for fra(X)-linked mental retardation (Martin-Bell syndrome). Three cases were diagnosed as affected after cytogenetic analysis of fetal blood and placental cultures. The fra(X)(q27.3) and common fragile sites were shown to be expressed at a lower level in placenta than in fetal blood. Induction methods included methotrexate, 5-fluoro-2-deoxyuridine, and excess thymidine. Excess thymidine may give the best expression of fra(X)(q27.3). Enhancement of fra(X)(q27.3) expression was not shown with caffeine or 5-methoxybenzamide.

Chorionic Villi Sampling↗
PubMedDate not supplied

Prenatal diagnosis of X-linked mental retardation with fragile (X) using fetoscopy and fetal blood sampling.

Pure fetal blood, (uncontaminated with maternal blood), was obtained from two male fetuses at risk for X-linked mental retardation with fragile(X) at Xq27-28 by direct vision fetoscopy and fetal blood sampling. Both were shown to have this fragile site on the X chromosome while nine other fetal blood samples from pregnancies at risk for other X-linked diseases, or haemoglobinopathies did not show fragile sites at Xq27-28, and a blood sample from an abortus showed only 1 fragile site in 95 mitoses. Both pregnancies were terminated, cultures established from fetal tissues, and the diagnosis confirmed in each case. The problems of demonstrating the fragile site in tissues other than fetal blood in these pregnancies (such as amniotic fluid cells or fibroblasts from fetal tissues) are discussed.

Adult↗
PubMedDate not supplied

Leber's hereditary optic neuropathy and Kearns-Sayre syndrome: mitochondrial DNA mutations.

Mitochondrial DNA (mt DNA) supplies extranuclear (cytoplasmic) genes which program the manufacture of 13 of the 67 peptides of the mitochondrial respiratory enzymes. The remaining 54 are coded by nuclear DNA. All human children and adults, male and female, are entirely dependent on the cytoplasm of the ovum for their complement of mt DNA; the sperm contributes none. Accordingly, mutations in the mt DNA in a mother's ova will be passed on to all her children, although not all are clinically affected. Leber's hereditary optic neuropathy is in most cases due to a mutation that leads to the replacement of guanine by adenine at position 11778 in mt DNA. This causes histidine to be inserted instead of the normal arginine at the site of the 340th amino acid in the respiratory enzyme NADH subunit 4, hence its defective function. Other point mutations in the mt DNA coding for polypeptides of the respiratory chain complex or controlling sequences coded by mt DNA have been found in other families with Leber's hereditary optic neuropathy. Mitochondrial DNA is the site of other mutations as well. For ophthalmologists, the most important of these is the rare Kearns-Sayre syndrome (pigmentary retinopathy plus muscular dystrophies, especially of the extraocular muscles). Kearns-Sayre syndrome is due to deletions in the mt DNA, which vary in size and so affect a number of different respiratory enzymes, hence the variable manifestations. Cases are usually sporadic because the disease is often so severe that affected individuals do not reproduce if they survive, but in some cases inheritance from the mother has been reported.

Chromosome Aberrations↗