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S Holloway

Publications and source records attributed to S Holloway.

At least 19 recordsLinked to original sources
PubMed1992

An exclusion map for pre-eclampsia: assuming autosomal recessive inheritance.

Pre-eclampsia is a common complication of the second half of pregnancy that is associated with substantial fetal and maternal morbidity. Although the genetic basis of the disorder is unclear, epidemiological studies suggest that it occurs predominantly in the first pregnancies of women who are homozygous for a relatively common susceptibility gene. Using this epidemiological model, we have begun to construct an exclusion map by using both candidate genes and random DNA markers on a panel of two-generation families in which pre-eclampsia was rigorously defined. No evidence was found for linkage to the HLA region or to several genes implicated in the pathogenesis of hypertension.

Chromosomes, Human, Pair 1↗
PubMed1991

What do young people think about screening for cystic fibrosis?

We investigated the knowledge of cystic fibrosis and the views about neonatal and carrier screening in 216 school students aged 14 to 16 years. This work was completed before the published identification of the cystic fibrosis gene in September 1989. Although initial knowledge of cystic fibrosis was low (only 17% of the students knew that the disease affected the lungs), there was good recall of basic information about cystic fibrosis and of recessive inheritance after a brief lecture. A total of 86% considered that carrier detection should be offered routinely and 88% felt that an offer of prenatal diagnosis for cystic fibrosis should be made if both prospective parents were known to be carriers. We believe that pilot studies of cystic fibrosis carrier screening in schools should be undertaken.

Adolescent↗
PubMed1991

Linkage disequilibrium and recombination make a telomeric site for the Huntington's disease gene unlikely.

In a Scottish family in which Huntington's disease (HD) was segregating, recombination was observed between the D4S115/S111 and D4S43/S95 loci, with the HD gene associated with the more proximal D4S43/S95 locus. Analysis of linkage disequilibrium in Scottish families showed significant non-random association between the HD gene and alleles at the D4S95 and D4S98 loci. This adds to previous evidence that the HD locus is not sited at the telomere of chromosome 4.

Alleles↗
PubMed1990

First-trimester maternal serum biochemical indicators in Down syndrome.

A set of 21 early maternal serum samples (19 first-trimester and two at 14 weeks) from pregnancies resulting in a child with Down syndrome was matched for gestation and length of storage with 63 samples from unaffected pregnancies. The concentrations of alpha-fetoprotein (AFP), unconjugated oestriol (uE3), human chorionic gonadotrophin (hCG), pregnancy-specific beta 1-glycoprotein (SP1), and placental alkaline phosphatase (PALP) were measured. The ratios of the medians for Down syndrome pregnancies compared with the medians for controls were AFP 0.71, uE3 0.67, hCG 1.43, SP1 0.79, and PALP 0.92. Although the differences between the medians for affected and unaffected pregnancies were not significant, the trends for AFP, uE3, and hCG confirm earlier findings on first-trimester samples.

Alkaline Phosphatase↗
PubMed1989

Predictive testing for Huntington's disease with linked DNA markers.

Availability of new DNA markers, more tightly linked to the Huntington's disease (HD) locus than the original G8 (D4S10) probes, has improved predictive accuracy for both presymptomatic and prenatal exclusion testing. 50 predictive tests were carried out on high-risk individuals. 6 of these were on first-trimester chorionic villus biopsy specimens; in 2 cases the HD gene was not transmitted to the fetus while in 4 cases no exclusion could be made. The remaining 44 tests were on adults with either 25 or 50% risk of manifesting the disease; 19 had a greatly increased risk and 25 a substantially decreased risk of HD. Family structures in Scotland are suitable for testing about 75% of potentially affected individuals, and the new generation of DNA markers makes virtually all families fully informative.

Adult↗
PubMed1989

Risks of fetal cystic fibrosis based on linkage disequilibrium data.

First-trimester prenatal diagnosis of cystic fibrosis depends on tissues being available from a previous affected child for determination of the phase relationship of DNA markers. If no such tissues are available, it is possible to estimate the risks of a couple producing an affected child from the distribution of haplotypes showing linkage disequilibrium with the cystic fibrosis gene. We have calculated all the fetal risk subsets from the various parental haplotype combinations for the restriction fragment length polymorphisms identified by the KM.19/PstI and XV-2c/TaqI systems. We conclude that only in a limited number of parental combinations are the fetal risks sufficiently high or sufficiently low to be used in prenatal diagnosis.

Cystic Fibrosis↗
PubMed1989

Presymptomatic testing for Huntington's disease. A case complicated by recombination within the D4S10 locus.

Presymptomatic testing for Huntington's disease (HD) is possible through the use of restriction fragment length polymorphisms (RFLPs) at the closely linked D4S10 locus. Recombination between the HD and D4S10 loci will occur in 4%-5% of meioses, and is a well-recognised complication of predictive testing. Recombination between RFLPs within the D4S10 locus is a rare event and can usually be ignored. We report a case where such an intra-locus recombination frustrated attempts to predict the chance of a high-risk individual inheriting the HD gene.

Adult↗
PubMed1989

Genetic linkage between Huntington's disease and D4S10 (G8) in Scottish families.

Genetic linkage between Huntington's disease (HD) and polymorphic DNA markers at the D4S10 locus has been investigated in 16 Scottish families. A maximum lod score of 3.499 at a recombination fraction of 0.07 was found, with 95% confidence limits of 0.02 and 0.22. Only one obvious recombinant was detected, and the wide confidence limits probably reflect the large number of unaffected individuals whose risk could only be estimated empirically.

Chromosomes, Human, Pair 4↗
PubMed1989

Prenatal exclusion testing for Huntington's disease: a problem of too much information.

At eight weeks of pregnancy a couple were informed that the prospective father's mother had died of Huntington's disease (HD). There were no living affected members in the immediate family to confirm the diagnosis. By inspection of the local genetic register, it was established that it was indeed HD segregating in the extended family. Genotyping of the prospective mother and father, the father's unaffected father, and his unaffected maternal grandmother was carried out using a battery of polymorphic DNA markers, including a new probe which has a very low recombination rate with the HD locus. Analysis of DNA from a chorionic villus sample taken at 10 weeks of pregnancy showed that the fetus must have inherited a chromosome from its father's affected mother. Its risk of developing HD was 47%. If the genotype of the unaffected maternal grandmother was taken into account, the risk was reduced to 42%. Neither risk was considered acceptable by the prospective parents and the pregnancy was terminated at 12 weeks' gestation. Prospects for future pregnancies are good, with a 50% chance of having a child whose risk of inheriting the HD gene is less than 1.5%. In retrospect it was noted that although genotyping of the maternal grandmother had refined the fetal risk, it had also nearly contributed to an inadvertent and unwanted predictive test for HD on the father. This case makes the point that in prenatal exclusion testing, linkage information must be generated with considerable care.

Adult↗
PubMed1988

Changes in maternal age distribution and their possible impact on demand for prenatal diagnostic services.

Between 1977 and 1985 there was a 65% increase in births to women aged 35 or more in England and Wales, but only a 15% increase in all births. Two factors of roughly equal importance were responsible for this differential increase. Firstly, the proportion of older women (35-44) among all women of reproductive age (15-44) increased from 28% in 1977 to 31% in 1985; and, secondly, in the same period the fertility rate for women aged 35-39 increased from 18.2 to 24.1 per 1000 and for women aged 40-44 from 4.1 to 4.6 per 1000. The increased fertility rate among older women is not due to an extension of the reproductive period but to a delay in childbearing. This delay was seen in women married only once and also in those who had remarried. As prenatal diagnosis for the exclusion of chromosome abnormalities is customarily offered to older mothers the increased numbers of women aged 35 or more and their increased fertility rate have important implications for the provision of obstetric and laboratory services. There were 51,859 live births to women aged 35 and over in 1985; the projected figure for 2001 is 85,000. If the use of prenatal diagnosis continues to increase facilities for about 70,000 prenatal cytogenetic analyses will be needed in 2001.

Adult↗
PubMed1988

First-trimester prenatal diagnosis of cystic fibrosis using fibroblasts from a deceased index child to establish haplotypes.

First-trimester prenatal diagnosis of cystic fibrosis (CF) using linked DNA markers is usually only possible if there is an index affected child to establish the haplotype of the parental chromosomes. We describe a prenatal diagnosis where fibroblasts, cultured from the skin of a deceased affected child and then held in frozen storage for 3 years, were used as the starting point for tracking the CF gene. The fetus was diagnosed as a homozygous normal and the diagnosis confirmed by immunoreactive trypsin testing after birth. It was also possible to establish heterozygosity in the aunt of the affected child.

Adult↗
PubMed1988

Use of linkage disequilibrium data in prenatal diagnosis of cystic fibrosis.

Parents at risk of bearing a child with cystic fibrosis, and who have no living affected child, often use prenatal diagnosis based on microvillar enzyme assay in second-trimester amniotic fluid samples. If enzyme levels are abnormal and the pregnancy is terminated, it is possible in principle to use the fetal tissues to establish the phase relationship of linked DNA markers for a subsequent first-trimester prenatal diagnosis. However, the probability of a fetus being affected after an abnormal microvillar enzyme test may be no greater than 80%. The strong linkage disequilibrium between haplotypes at the D7S23 locus and the cystic fibrosis gene may be used to increase this probability. If fetal tissues are homozygous for the 6.6-kb band defined by pKM.19 and PstI and also homozygous for the 2.1-kb band with pXV-2c and TaqI, the chance of being affected increases from 80% to between 95% and 97%. We regard this as being sufficiently certain for use in phase determination.

Cystic Fibrosis↗
PubMed1986

Probably Norrie's disease due to mutation. Two sporadic sibships of two males each, a necropsy of one case, and, given Norrie's disease, a calculation of the gene mutation frequency.

Two sibships, each with two affected males but no other affected family members, are described. All four patients at birth had small eyes with white masses visible behind clear lenses. Support for a diagnosis of Norrie's disease lies in the probable mental retardation and sudden death of one child and mental retardation in the other in one of the families, and strong support in the sensorineural deafness in one child in the other family. A necropsy was performed on the dead child. Both eyes showed the retinae to be totally non-attached. The optic nerves were thin. If the diagnosis is Norrie's disease (highly probable), the birth of the second affected child in each family supports the postulate of a mutation in the X chromosome of a germ cell of a maternal grandparent or an earlier maternal ancestor, no previous member of the family having been affected. That implies a 50% risk of the disease in future male siblings and a 50% risk of the carrier state in female sibs. When only one child is affected, the explanation could also be a mutation in that individual. Given Norrie's disease, we have calculated a mutation rate of 3.9 per million chromosomes in the Scottish population--remarkably similar to the mutation rates calculated for many dominant diseases. A diagnosis of autosomal recessive non-attachment of retina implies a 25% risk to later siblings.

Blindness↗
PubMed1979

Prospective study of genetic counselling.

A prospective study was carried out on 200 consecutive subjects seen for counselling (consultands) for serious genetic disorders. Educational and social background of consultands and their knowledge and understanding of their particular problem were assessed before counselling, and their response was determined immediately afterwards and three months and two years later by an independent observer not concerned in the genetic counselling. The husband's educational background was particularly important in influencing a couple's comprehension of counselling. X-linked recessive and chromosomal disorders presented the most difficulties in comprehension. The counsellors' assessment of comprehension was a good guide to the consultands' comprehension as assessed at subsequent follow-up. The proportion deterred from having children increased with time and over a third had been sterilised within two years of counselling. It is suggested that follow-up after counselling should be routine, especially when the counsellor suspects that comprehension has not been good, in X-linked recessive and chromosomal disorders, and when the risks of having an affected child are considered to be high.

Adult↗