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H Gurling

Publications and source records attributed to H Gurling.

At least 37 records · Page 2Linked to original sources
PubMed1994

A linkage study of affective disorder with DNA markers for the ABO-AK1-ORM linkage group near the dopamine beta hydroxylase gene.

Combining data from a number of studies has provided evidence for a susceptibility allele for affective disorder near to the ABO-AK1-ORM region on chromosome 9q34. The dopamine beta hydroxylase gene locus is also at 9q34. Five multigenerational families with bipolar and unipolar affective disorder were analyzed for linkage with highly polymorphic microsatellite markers from the candidate region. The segregation of the illness in these families was compatible with an autosomal dominant susceptibility allele. Linkage analyses using conservative parameters seemed to provide strong evidence against a major susceptibility allele in this region including the candidate gene dopamine beta hydroxylase in these families.

ABO Blood-Group System↗
PubMed1994

Oligonucleotides as short as 7-mers can be used for PCR amplification.

Amplification of DNA sequences using the polymerase chain reaction (PCR) requires as primers two oligonucleotides, which are carefully designed for length and G/C content. Such primers are generally between 18 and 30 bases long so that the primer sequences can amplify a unique sequence in the target genome; they should possess a minimal degree of secondary structure. We have tested the minimum length of G/C-rich and palindromic oligonucleotides to be used as primers in PCR. Oligonucleotides with sequences corresponding to the recognition sites of rare restriction enzymes were used on the DNA of vector constructs as model template DNA. Surprisingly, we found specific amplification with a low background over a wide range of temperatures for oligonucleotides as short as 7 nucleotides. This findings contradicts the previously reported empirical relationship between oligonucleotide length and ability to trigger amplification and points to the complex relationship between thermodynamic and kinetic criteria in relation to PCR. This technique should lead to new application in the cloning and screening of complex genomes.

Base Sequence↗
PubMed1993

Linkage between tyrosine hydroxylase gene and affective disorder cannot be excluded in two of six pedigrees.

Genetic linkage between manic depression and DNA markers on the short arm of chromosome 11 was first reported in 1987 but not supported by further analyses. However, genetic markers at the tyrosine hydroxylase (TH) gene located within this region have been reported to show allelic association with the affective disorder phenotype. We present the results of a linkage analysis using polymorphic DNA segments within the TH gene and the nearby dopamine D4 receptor (DRD4) gene in 6 families multiply affected with affective disorder. Small positive Lod scores were obtained in 2 of 6 pedigrees with the TH polymorphism which may be indicative of genetic heterogeneity.

Female↗
PubMed1993

Refined linkage map of chromosome 5 in the region of the spinal muscular atrophy gene.

The genetic map in the region of human chromosome 5 that harbors the gene for autosomal recessive forms of spinal muscular atrophy (SMA) has been refined by a multilocus linkage study in 50 SMA-segregating families. Among six markers spanning 8 cM for combined sexes, four were shown to be tightly linked to the SMA locus. Multipoint linkage analysis was used to establish the best estimate of the SMA gene location. Our data suggest that the most likely location for the SMA locus is between blocks AFM114ye7 (D5S465)/EF5.15 (D5S125) and MAP-1B/JK53 (D5S112) at a sex-combined genetic distance of 2.4 and 1.7 cM, respectively. Thus the SMA gene lies in the 4-cM region between these two blocks. This information is of primary importance for designing strategies for isolating the SMA gene.

Base Sequence↗
PubMed1993

Cloning of the human dopamine D5 receptor gene and identification of a highly polymorphic microsatellite for the DRD5 locus that shows tight linkage to the chromosome 4p reference marker RAF1P1.

We identified a cosmid clone with exact sequence homology to part of the human dopamine D5 receptor gene (DRD5) after screening a cosmid library with the human DRD1 gene. The dopamine D5 receptor was mapped to chromosome 4p15.1-p15.3 by in situ hybridization and using a somatic cell hybrid panel. We report here the further localization of the DRD5 gene following identification of a highly polymorphic dinucleotide repeat sequence in the cosmid clone. The microsatellite (D5(CT/GT/GA)n) had 12 alleles with a polymorphic information content value of 0.77. Linkage analysis in 39 CEPH pedigrees demonstrated tight linkage to the chromosome 4p reference marker RAF1P1 (Zmaxf 20.66 at theta f 0.05 and ZmaxM 16.57 at theta m 0.07).

Base Sequence↗
PubMed1991

No evidence for a susceptibility locus predisposing to manic depression in the region of the dopamine (D2) receptor gene.

Recent reports of cytogenetic abnormalities linked to psychiatric illness and the localisations of the genes for the dopamine (D2) receptor and tyrosinase on the long arm of chromosome 11 have suggested that susceptibility loci for schizophrenia and manic depression might be situated in this region. We could find no evidence for linkage in five Icelandic pedigrees between manic depression and markers in this region, and we have excluded candidate genes coding for the D2 receptor and tyrosinase. We conclude that mutations at loci in this region are not a common cause of manic depression in the population studied.

Adult↗
PubMed1991

Linkage disequilibrium between two highly polymorphic microsatellites.

The PCR was used to amplify genomic DNA from two microsatellite (dC-dA)n.(dG-dT)n sequences found to be present in the same chromosome 5 genomic clone. Analysis of the haplotype frequencies of these two interspersed repeat sequences in individuals showed strong allelic association or linkage disequilibrium. Six alleles were found for p599 (CA)n with a PIC value of 0.71 and 8 alleles were seen for lambda 599 (CA)n with a PIC value of 0.74. The two microsatellites are separated by approximately 7 kb. Analysis of the length variations for the two microsatellites showed that they were positively correlated, a finding that has no obvious explanation. The strong linkage disequilibrium found demonstrates stability during evolution for these novel markers. Therefore they should be powerful new tools for studying genetic drift and admixture of populations. Furthermore, disequilibrium data from microsatellites can be used in the fine mapping and cloning of disease genes.

Alleles↗
PubMed1989

Exclusion of linkage to 5q11-13 in families with schizophrenia and other psychiatric disorders.

Recently a linkage study on five Icelandic and two English pedigrees has provided evidence for a dominant gene for schizophrenia on 5q11-13 (ref. 1). In that study, families with bipolar illness were not included. Using the same probes, two similar but independent investigations on one Swedish pedigree and on fifteen Scottish families excluded linkage to schizophrenia. To evaluate whether the susceptibility gene on 5q11-13 is a common cause of schizophrenia in other populations, we examined five affected North American pedigrees using probes to the D5S39, D5S76 and dihydrofolate reductase loci. Two families in the present series had cases of bipolar disorder. We found that linkage can be excluded by multipoint analysis. These results, taken together, suggest that the disease gene on 5q11-13 does not account for most cases of familial schizophrenia.

Bipolar Disorder↗
PubMed1988

Localization of a susceptibility locus for schizophrenia on chromosome 5.

Schizophrenia is a common disorder with a life time prevalence of approximately 1 per cent. The illness often develops in young adults, who were previously normal, and is characterized by a constellation of symptoms including hallucinations and delusions (psychotic symptoms) and symptoms such as severely inappropriate emotional responses, a disorder of thinking and concentration, erratic behaviour as well as social and occupational deterioration. A considerable proportion of the variance in the liability to develop schizophrenia may be genetic, but segregation analysis, to establish a mode of transmission, has not produced a consistent result. One of these studies was carried out in Iceland and made use of the large family size and extensive geneaological information present in that country. Here we demonstrate genetic linkage of two DNA polymorphisms on the long arm of human chromosome 5 to schizophrenia in seven British and Icelandic families with multiple affected members. The results indicate the existence of a gene locus with a dominant schizophrenia-susceptibility allele. Inheritance of the allele in the families studied suggests that it may also predispose to psychiatric conditions such as schizophrenia spectrum disorders and a variety of other disorders. This report provides the first strong evidence for the involvement of a single gene in the causation of schizophrenia.

Chromosomes, Human, Pair 5↗
PubMed1986

Candidate genes and favoured loci: strategies for molecular genetic research into schizophrenia, manic depression, autism, alcoholism and Alzheimer's disease.

It is argued that further research to achieve more detailed diagnostic systems in many psychiatric disorders is unlikely to be productive without taking genetic effects into account. Even when this is done, for example when carrying out segregation analysis to determine a mode of genetic transmission, mental illnesses often pose specific problems that preclude accurate analysis. Because techniques in molecular biology and genetics have made it possible to study gene effects in human disease systematically it should now be possible to specify the genes that are involved. When this has been achieved then a diagnostic system based on genetic causation can develop. This will have the advantage of helping to pinpoint environmental factors more accurately. Specific strategies will need to be adopted to overcome uncertain modes of inheritance, incomplete or non-penetrance of disease alleles and disease heterogeneity. Highly speculative hypotheses can be put forward for a locus causing Alzheimer's disease on a portion of the long arm of chromosome 21. For autism it is plausible that there is a disease locus at or near the fragile X site on the X chromosome. A locus for manic depression has been very tentatively mapped using DNA markers to chromosome 11 and in a small proportion of families DNA markers have also shown some evidence for X linkage. Schizophrenia does not seem to be associated with any favoured loci. Candidate genes for schizophrenia include those encoding dopamine, other neurotransmitter receptors or enzymes and various neuropeptides such as enkephalin and beta endorphin.

Alcoholism↗