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J M Connor

Publications and source records attributed to J M Connor.

At least 19 recordsLinked to original sources
PubMed1992

Tightly linked polymorphic markers for fragile X syndrome and prenatal cytogenetic diagnostic experience.

Linkage analysis using the polymorphic loci DXS369, DXS296, DXS297 and DXS306 was carried out on a cohort of 17 families segregating for fragile X syndrome. The observed recombination fractions at: DXS369 (Zmax = 3.02; theta = 0.06), DXS297 (Zmax = 2.92; theta = 0.0), DXS296 (Zmax = 3.82; theta = 0.0), DXA306 (Zmax = 4.55; theta = 0.05) confirm that these loci are tightly linked to FRAXA. Our experience in the cytogenetic analysis of 58 at risk pregnancies by chorionic villus or fetal blood sample examination documents a false negative rate in obligate carrier male pregnancies for CVS of 11% and for FBS of 3%.

Cytogenetics↗
PubMed1992

Fibrinogen genotype and risk of peripheral atherosclerosis.

There is conflicting evidence about the influence of fibrinogen genotype on plasma fibrinogen concentrations, and the relation between genotype and atherosclerotic disease has not been studied. In a population-based case-control study we aimed to find out whether certain fibrinogen genotypes are associated with an increased risk of peripheral atherosclerosis. 121 subjects with peripheral arterial disease and 126 healthy controls matched for age and sex were selected from a random population sample aged 55-74 years in the Edinburgh Artery Study. Mean fibrinogen concentrations were higher in cases than in controls (3.12 [95% confidence interval 2.99-3.26] vs 2.75 [2.64-2.85], p less than 0.001). A greater proportion of cases than controls were homozygous or heterozygous for an allele at the beta fibrinogen locus (4.2 kb allele, Bcl I digestion); the allele frequency was 0.197 in cases and 0.097 in controls (p less than 0.005). Extended haplotypes for 4.2 kb heterozygotes were also associated with an increased risk of peripheral arterial disease. However, haplotype had only a small effect on the association of plasma fibrinogen concentration with disease, and the relation of haplotype with disease was independent of age, sex, social class, smoking status, plasma fibrinogen, alcohol consumption, body mass index, and diabetes mellitus. We conclude that variation at the beta fibrinogen locus is associated with an increased risk of peripheral atherosclerosis. The influence is not mediated simply by way of increased fibrinogen concentrations but could be due to a structurally variant fibrinogen or linkage disequilibrium with a neighbouring gene.

Aged↗
PubMed1992

The psychosocial sequelae of a second-trimester termination of pregnancy for fetal abnormality.

A retrospective study to investigate the psychosocial sequelae of a second-trimester termination of pregnancy (TOP) for fetal abnormality (FA) is described. After appropriate consent was obtained, 84 women and 68 spouses were visited 2 years after the event and asked to complete an extensive questionnaire. Most couples reported a state of emotional turmoil after the TOP. There were differences in the way couples coped with this confusion of feelings. After 2 years about 20 per cent of the women still complained of regular bouts of crying, sadness, and irritability. Husbands reported increased listlessness, loss of concentration, and irritability for up to 12 months after the TOP. In the same period, there was increased marital disharmony in which 12 per cent of the couples separated for a while and one couple obtained a divorce. These problems could be attributed to a lack of synchrony in the grieving process. Confusing and conflicting feelings led to social isolation and lack of communication. Difficulties in coming to terms with the fetal loss were not found to be linked to the type of fetal abnormality or religious beliefs but were related to parental immaturity, inability to communicate needs, a deep-rooted lack of self-esteem before the pregnancy, lack of supporting relationships, and secondary infertility. Suggestions for improved management are given.

Abortion, Therapeutic↗
PubMed1992

Variation in the levels of pregnancy-specific beta-1-glycoprotein in maternal serum from chromosomally abnormal pregnancies.

Human pregnancy-specific beta-1-glycoprotein (SP1) was assayed retrospectively in stored maternal serum (MS) samples from 82 chromosomally abnormal pregnancies and 377 matched controls. The median MSSP1 concentration in 48 Down's syndrome pregnancies was significantly elevated at 1.17 multiples of the control median (MOM), and significantly reduced (0.5 MOM) in a group of eight cases of unbalanced translocations. There was no significant difference in median SP1 concentrations in cases of trisomy 18, trisomy 13, balanced translocations, or sex chromosome abnormalities. A comparison with human chorionic gonadotrophin results in the same series of samples indicates that SP1 is a less sensitive predictor of Down's syndrome pregnancies.

Chorionic Gonadotropin↗
PubMed1992

Evidence for genetic heterogeneity in hereditary hydronephrosis caused by pelvi-ureteric junction obstruction, with one locus assigned to chromosome 6p.

Hereditary hydronephrosis (MIM 143400) is an autosomal dominant trait that causes unilateral or bilateral pelvi-ureteric junction (PUJ) obstruction. Linkage analysis was undertaken in 5 families with hereditary PUJ obstruction using the major histocompatibility complex locus as a test marker. The data as a whole supported a hereditary hydronephrosis locus on 6p. Maximal lod scores were 3.090 at a recombination fraction of 0.1 with full penetrance, and 2.486 at a recombination fraction of 0.1 with a penetrance of 90%. However, analysis of two point lod scores using the HOMOG program revealed significant evidence for genetic heterogeneity with one locus on 6p in 4 of the families, and a different locus in one family. After exclusion of this unlinked family, two point analysis gave a maximal lod score of 3.9 at a recombination fraction of 0.05 with full penetrance, and 4.2 at a recombination fraction of 0.0 with 90% penetrance. These data support the assignment of one of the loci for hereditary hydronephrosis to chromosome 6p.

Chromosomes, Human, Pair 6↗
PubMed1992

A YAC contig in Xp21 containing the adrenal hypoplasia congenita and glycerol kinase deficiency genes.

The gene loci for adrenal hypoplasia congenita (AHC) and glycerol kinase deficiency (GK) map in Xp21 distal to Duchenne muscular dystrophy (DMD), and proximal to DXS28 (C7), by analysis of patient deletions. We have constructed a yeast artificial chromosome (YAC) contig encompassing a 1.2 Mb region extending distally from DMD, and containing DXS708 (JC-1), the distal junction clone of a patient with GK and DMD. A pulsed-field gel electrophoresis map of the YAC contig identified 3 potential CpG islands. Whole YAC hybridization identified cosmids both for construction of cosmid contigs, and isolation of single copy probes. Thirteen new single copy probes and DXS28 and DXS708 were hybridized on a panel of patients; the deletion mapping indicates that the YAC contig contains both GK and at least part of AHC, and together with the physical map defines a GK critical region of 50-250 kb. In one AHC patient with a cytogenetically detectable deletion we used the new probes to characterize a complex double deletion. Non-overlapping deletions observed in other unrelated AHC patients indicate that the AHC gene is large, extending over at least 200-500 kb. This mapping provides the basis for the identification of the AHC and GK genes.

Adrenal Gland Diseases↗
PubMed1992

Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure.

AIM: To assess the feasibility and utility of a new method to identify factors associated with increased predisposition to high blood pressure in young people. SUBJECTS: Eight hundred and sixty-four people aged 16-24 years and their parents. SETTING: Ladywell Medical Centre, Edinburgh, Scotland, UK. METHOD: Blood pressure was measured in 864 young adults and in both of their parents. Four groups of approximately 50 offspring were selected from the corners of a scatter diagram, with offspring blood pressure scores on one axis and combined parental blood pressure scores on the other. Blood and urine samples were taken for biochemical and genetic analyses. RESULTS: Two groups of offspring had parents with high blood pressure and two groups had parents with low blood pressure. When parental blood pressure was low, comparison of offspring with high and low blood pressure revealed significantly higher mean body mass index in offspring with high blood pressure, but no significant elevation of biochemical or hormonal variables. When parental blood pressure was high, comparison of offspring with high and low blood pressure also revealed a significant difference in body mass index, but in addition, offspring with high blood pressure and high parental blood pressure had higher levels of angiotensinogen, cortisol and 18-OH corticosterone. Restriction fragment length polymorphism analysis revealed that 27% of offspring at the greatest genetic risk (high personal and parental blood pressure) were homozygous for the larger allele of the glucocorticoid receptor gene compared with only 9% of those at lowest genetic risk (low personal and parental blood pressure). CONCLUSION: The combined biochemical and genetic findings suggest that abnormalities of glucocorticoid metabolism and the renin-angiotensin system may help to explain genetic predisposition to high blood pressure. The new sampling method is practicable and could be applied to the investigation of other continuously distributed variables which show familial aggregation.

Adolescent↗
PubMed1992

Genetic variation at fibrinogen loci and plasma fibrinogen levels.

In view of the controversy regarding genetic variation at the fibrinogen loci and plasma fibrinogen levels, we have analysed DNA polymorphisms at the alpha (TaqI), beta (BclI and HaeIII), and gamma (KpnI/SacI) fibrinogen loci in 247 subjects whose plasma fibrinogen was determined by clotting and nephelometric assays. Strong linkage disequilibrium was found between the alpha/TaqI and gamma/KpnI/SacI markers and between the beta/BclI and beta/HaeIII markers. A lesser association was found between the alpha/TaqI and beta/BclI loci, beta/BclI and gamma/KpnI/SacI markers, alpha/TaqI and beta/HaeIII markers, and the gamma/KpnI/SacI and beta/HaeIII markers. This is consistent with the known physical order of these loci and suggests a relative excess of recombination in the alpha/gamma to beta interval. Plasma fibrinogen levels, by either assay method, when corrected or uncorrected for age, sex, and smoking habit, did not show any statistically significant associations with the four fibrinogen polymorphisms examined at the alpha, beta, and gamma fibrinogen loci either singly or when analysed as a haplotype.

Blotting, Southern↗
PubMed1991

Prenatal screening for chromosome abnormalities using maternal serum chorionic gonadotrophin, alpha-fetoprotein, and age.

Human chorionic gonadotrophin (hCG) levels were assayed retrospectively in stored maternal serum samples from 78 chromosomally abnormal pregnancies and 410 controls matched for gestation and maternal age. The median serum hCG concentration in 49 pregnancies with Down's syndrome was significantly elevated, at 2.18 multiples of the normal median. Significantly reduced hCG concentrations were found in a group of four trisomy 18 pregnancies (all less than 0.4 multiples of the median). Eight cases of unbalanced chromosome rearrangements appeared to show some lowering of hCG levels, while there was no significant difference in the levels in the cases of trisomy 13, balanced translocations, and sex chromosome abnormalities. Maternal serum hCG alone is a better indicator of Down's syndrome pregnancies than maternal age or maternal serum alpha-fetoprotein (AFP), either individually or in combination, and provides a further virtually independent measure of risk. On the basis of our findings, screening for Down's syndrome using hCG and AFP results combined with maternal age risks is predicted to result in a higher detection rate (57 per cent) for a lower false-positive rate (5.0 per cent) than would be attainable by combined AFP and age screening (37 per cent detection at a 6.6 per cent false-positive rate).

Chorionic Gonadotropin↗
PubMed1991

Chromosomal assignment of a large tRNA gene cluster (tRNA(Leu), tRNA(Gln), tRNA(Lys), tRNA(Arg), tRNA(Gly)) to 17p13.1.

A cluster of tRNA genes (tRNA(UAGLeu), tRNA(CUGGln), tRNA(UUULys), tRNA(UCUArg)) and an adjacent tRNA(GCCGly) have been assigned to human chromosome 17p12-p13.1 by in situ hybridization using a 4.2 kb human DNA fragment for tRNA(Leu), tRNA(Gln), tRNA(Lys), tRNA(Arg), and, for tRNA(Gly), 1.3 kb and 0.58 kb human DNA fragments containing these genes as probes. This localization was confirmed and refined to 17p13.100-p13.105 using a somatic cell hybrid mapping panel. Preliminary experiments with the biotinylated tRNA Leu, Gln, Lys, Arg probe and metaphase spreads from other great apes suggest the presence of a hybridization site on the long arm of gorilla (Gorilla gorilla) chromosome 19 and the short arm of orangutan (Pongo pygmaeus) chromosome 19 providing further support for homology between HSA17, GGO19 and PPY19.

Animals↗
PubMed1991

Genetic heterogeneity in tuberous sclerosis. Study of a large collaborative dataset.

Tuberous sclerosis (TSC) is a multisystem autosomal dominant hamartosis whose genetics is complicated by reduced penetrance and widely varying clinical expression. Results of linkage analyses have variously suggested two different locations for a TSC gene. A collaborative dataset has been assembled to clarify the issue of genetic heterogeneity. We have now analyzed the data from a combined sample of 111 families. Using Ott's HOMOG programs, we completed three tests of homogeneity: (1) for chromosome 9q, (2) for chromosome 11q, and (3) for the combined 9q and 11q data. For test 1 the chi-square (1 df) was 21.54 (p less than 0.001), for test 2 the chi-square (1 df) was 0.13 (p greater than 0.35), and for test 3 the chi-square (2 df) was 37.61 (p less than 0.0001). Additionally, we examined the combined data for evidence that a third, as yet unlinked locus exists. Results of this last test were suggestive but not significant. Clearly loci for TSC are present on both chromosomes 9q and 11q. The maximum likelihood estimate of the proportion of chromosome 9q-linked families is 0.38, for chromosome 11q-linked families is 0.47, and for the unlinked type 0.15. Alternative explanations for these latter families include chance sampling of recombinants, nongenetic phenocopies, or misclassification.

Chromosomes, Human, Pair 11↗
PubMed1991

Recent linkage studies in tuberous sclerosis. Chromosome 9 markers.

After our initial reports 3-5 supporting a locus for tuberous sclerosis (TSC) on 9q, linkage analysis was undertaken in eight large multigeneration TSC families using nine polymorphic markers. Six of the markers were from the distal long arm of chromosome 9 and three from the long arm of chromosome 11. The data as a whole supported a TSC locus on distal 9q, the peak lod score on multipoint analysis being 3.77 6 cM proximal to the Abelson oncogene locus (ABL). However, analysis of 2-point lod scores using the HOMOG programs revealed significant evidence for genetic heterogeneity (p = 0.01), tight linkage to ABL being highly unlikely in one family. After exclusion of the unlinked family multipoint, analysis gave a peak lod score of 6.1 in the vicinity of ABL. The family unlinked to ABL showed no recombinants with two chromosome 11 probes, but it was too small to provide significant evidence for linkage. Genetic heterogeneity in TSC as demonstrated by this study will complicate efforts to clone the genes by reverse genetics and will severely hamper the use of linked probes for carrier detection and prenatal diagnosis.

Chromosomes, Human, Pair 9↗