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D Curtis

Publications and source records attributed to D Curtis.

At least 55 records · Page 3Linked to original sources
PubMed1999

Chromosome 21 workshop.

The report of the 1997 workshop presented overall evidence providing strong support for a susceptibility locus for bipolar disorder at C21q22-23. The 1998 workshop considered the latest results from four groups, and additional studies also have been incorporated into this report. The workshop noted that there was possibly a degree of overlap between the regions implicated by the large samples of the multiplex National Institute of Mental Health pedigrees (affected sib pair analysis: p = 0.0006) and the US/Israeli pedigrees of the New York group (admixture lod = 3.35), in an area a few centimorgans proximal to PFKL. Participants concluded that the evidence implicating this region remains as strong as any, and were optimistic that further investigation would eventually lead to the identification of a susceptibility gene.

Bipolar Disorder↗
PubMed1999

A study of Wilson disease mutations in Britain.

Wilson disease (WD) is an autosomal recessive disease of copper transport. The disease is caused by a large number of mutations in the ATP7B gene, some of which appear to be population specific, whereas others are found in probands from a variety of different ethnic backgrounds. This study presents the results of screening the ATP7B gene by SSCP and sequencing in order to define the spectrum of mutations seen in British referrals for WD. The 52 patients screened included 10 with a non-British mixed ethnicity origin. This study identified 19 novel mutations and 18 mutations that had been previously described. The novel mutations included seven nonconservative missense mutations, eight small insertions, or deletions causing frameshift, two nonsense mutations, and two splice-site mutations. Seven of the 10 mixed ethnicity patients harboured homozygous mutations, whereas only four of the larger British group were homozygotes. The detection rate by SSCP analysis in the British group of 42 consecutive unrelated WD probands was 70%. However, SSCP screening of just three exons (exons 8, 14, and 18) is predicted to identify 60% of mutations present in WD referrals.

Adenosine Triphosphatases↗
PubMed1999

Comparison of GENEHUNTER and MFLINK for analysis of COGA linkage data.

We compared the NPLALL statistic from GENEHUNTER with two-point and three-point MALODs and MFLODs from MFLINK for all autosomal markers in the Collaborative Study on the Genetics of Alcoholism (COGA) data set. In general MFLINK produced more significant results than GENEHUNTER and implicated two regions containing candidate genes (ADH3 and DRD2). Many regions of interest identified in other studies reported at this workshop produced MALODs significant at p < or = 0.05, but these would not have been picked up by GENEHUNTER unless a less significant threshold were used.

Alcoholism↗
PubMed1999

Adjacent genetic markers on chromosome 11p15.5 at or near the tyrosine hydroxylase locus that show population linkage disequilibrium with each other do not show allelic association with bipolar affective disorder.

BACKGROUND: Linkage and association studies have suggested genetic susceptibility to bipolar affective disorder in a region of chromosome 11 around the tyrosine hydroxylase locus. We attempted to test the hypothesis that there was allelic association between polymorphisms around the tyrosine hydroxylase locus and bipolar affective disorder. METHODS: A case-control association study was employed using four polymorphic markers, which span a region of approximately 2 cM across the tyrosine hydroxylase locus. RESULTS: No evidence for allelic association between bipolar affective disorder and any of these markers was found. However, linkage disequilibrium between the markers was detected. CONCLUSIONS: This finding diminishes the probability that genes in this region influence susceptibility to bipolar affective disorder, at least in our sample.

Alleles↗
PubMed1999

Common HLA alleles, rather than rare mutants, confer susceptibility to coeliac disease.

Coeliac Disease (CD) is a gluten sensitive enteropathy characterised by villous atrophy and crypt cell hyperplasia. It has a very strong HLA class II association to the DQ locus. The nature of the involvement of the DQ locus in the susceptibility to CD has been examined by tissue culture experiments, association and peptide binding studies. We examined the role of the DQ molecules in the pathogenesis from the perspective of a genetic family study. Using flanking microsatellite markers to the class II region of the MHC to establish the parental origin of the susceptibility DQ alleles, we have evidence suggesting that the HLA association is probably due to the necessity to have these DQ alleles in order to express CD and there is no support for the presence of a rare mutation within the DQ alleles nor any rare HLA-linked gene nearby in linkage disequilibrium with the DQ locus. This approach is applicable to other diseases demonstrating strong association with common alleles, and can be used to predict whether screening the region for rare mutations is likely to be worthwhile.

Alleles↗
PubMed1999

New DNA markers with increased informativeness show diminished support for a chromosome 5q11-13 schizophrenia susceptibility locus and exclude linkage in two new cohorts of British and Icelandic families.

Genetic linkage of schizophrenia to markers at 5q11.2-13.3 had been reported previously in five Icelandic and two British families, but attempts at replication in independent samples have been unsuccessful. We report here an update on the diagnoses and results of linkage analyses using newer highly polymorphic microsatellite markers at or near the loci D5S76 and D5S39 in the original sample of pedigrees and in two new family samples from Iceland and from Britain. The new results show a reduction in evidence for linkage in the original sample and evidence against linkage in the two new family samples. Although it is possible that a rare locus is present, perhaps in the region 5p14.1-13.1 rather than 5q11.2-13.3, it appears most likely that the original positive lod scores represent an exaggeration of the 'true' lod scores due to random effects and that the small lod scores we now obtain could have arisen by chance.

Chromosomes, Human, Pair 5↗
PubMed1999

No evidence for linkage of schizophrenia to DXS7 at chromosome Xp11.

There have been claims that a gene on the X chromosome may contribute to susceptibility to schizophrenia. Crow (1988) initially proposed that such a gene might lie in the pseudoautosomal region, but when evidence that weakened this hypothesis accumulated, he proposed that a susceptibility locus might be present elsewhere on the sex chromosomes instead. DeLisi et al. (1994) found a small nonsignificant positive lod score between the marker DXS7 and schizophrenia, but other failed to replicate this finding. Another study reported by Crow and DeLisi's group was also weakly positive for this marker (Dann et al., 1997). This locus was then investigated in a collaborative study by Laval et al. (1997), which produced a nonparametric lod score of 2.44. Using a sample of 17 pedigrees from Britain and Iceland, we have also tested the hypothesis of linkage between DXS7 and schizophrenia. The 17 families were selected from a larger sample on the basis of an absence of male-to-male transmission for schizophrenia. These families were originally selected for having multiple cases of schizophrenia within them and for having no cases of bipolar affective disorder. We genotyped subjects for a marker at DXS7 and performed classical lod score and model-free linkage analysis using broad and narrow definitions of affection with schizophrenia. We found strongly negative lod scores and no evidence for linkage using model-free analysis. Therefore, this study does not support the hypothesis of linkage of schizophrenia to DXS7, and the evidence for a susceptibility locus on this part of the X chromosome is weakened.

Chromosome Mapping↗
PubMed1999

Family linkage study of the T-cell receptor genes in coeliac disease.

BACKGROUND: The susceptibility to coeliac disease is genetically determined by possession of certain HLA DQ alleles, together with a one or more non-HLA genes. The central role of the T-cell receptor in disease pathogenesis makes the T-cell receptor genes strong candidates as disease susceptibility genes, and previous studies had provided equivocal ambiguous results. METHODS: A pedigree based genetic linkage study was used to determine if any of the T-cell receptor genes have a role in the genetic aetiology of coeliac disease. Intragenic microsatellite markers were used to study T-cell receptor alpha, beta, and delta, while gamma was studied using two flanking microsatellites D7S484 and D7S629. RESULTS: Conventional linkage analysis was performed using the MLINK computer package. Model-free linkage analysis was performed using MFLINK. No evidence of linkage between coeliac disease and the T-cell receptor genes was found in these pedigrees. CONCLUSIONS: Mutations in the T-cell receptor genes are not implicated in the genetic aetiology of coeliac disease.

Base Sequence↗
PubMed1998

A pedigree-based linkage study of coeliac disease: failure to replicate previous positive findings.

Coeliac Disease (CD) is a gluten sensitive enteropathy characterised by villous atrophy and crypt cell hyperplasia. There is a tight HLA association between CD and the HLA DQ alleles DQA1*0501, DQB1*0201 (DQ2), arranged in either cis- or trans- configuration, are found in 98.9% of cases in Northern European populations and 80% in Greeks and Ashkenazi Jews resident in Israel. We have previously shown that the HLA alleles and CD do not co-segregate in families multiply affected with CD, suggesting that the HLA association is entirely due to the necessity to have these normal DQ alleles for CD to manifest, and that the main genetic predisposition lies at a locus other than the MHC. It is therefore possible to conduct genetic linkage studies in order to isolate the non HLA genes which predispose to CD. Recently a group conducted a genome screen for the non HLA genes in an affected sib-pair analysis and identified four non HLA loci with positive lod scores. We examined these loci using a pedigree based linkage study. Our pedigree sample consisted of a cohort of 21 families with 60 affected individuals and 125 unaffected family members. We used 11 microsatellite markers at the loci implicated and analysed the genotype data using both MLINK and MFLINK to detect linkage. The MLINK and MFLINK analyses did not provide any evidence to support the earlier findings, although the difficulties involved in analysing complex diseases mean that one cannot be certain that these regions do not harbour susceptibility loci, at least in some families.

Celiac Disease↗
PubMed1998

Linkage analysis between bipolar affective disorder and markers on chromosome X.

Since 1969, several classical linkage studies suggested an X-chromosome locus for bipolar affective disorder. However, methods using highly polymorphic DNA markers have provided conflicting evidence for linkage, and an X-chromosomal locus for bipolar disorder remains controversial. More recently, Pekkarinen et al. (1995) found a maximum LOD score of 3.54 at the marker DXS994 in a large bipolar Finnish kindred. In the present study, we attempted to replicate this finding using 43 families multiply affected by bipolar affective disorder. These families were selected for the absence of male-to-male transmission of the disease, and were genotyped for two microsatellte markers, DXS1227 and DXS1062 (which is about 2 cM telomeric to DXS994). Linkage to this region was excluded either using a two-point lod score method with two plausible genetic models, or by a model-free lod score analysis which does not require specification of a particular mode of transmission. We conclude that there is no evidence of a common major gene for bipolar affective disorder at Xq25-q27 in our set of families.

Bipolar Disorder↗
PubMed1998

Exclusion of the familial Mediterranean fever locus as a susceptibility region for autosomal dominant familial Hibernian fever.

Autosomal dominant periodic fevers constitute a range of syndromes characterised by recurrent attacks of fever and abdominal pain. Familial Hibernian fever (FHF) has been described in only one United Kingdom based family, but two other Irish families have been found with similar clinical features. FHF resembles familial Mediterranean fever (FMF) in several clinical features, but the mode of inheritance of FHF is dominant whereas FMF is recessive. We have investigated whether autosomal dominant periodic fevers, in particular FHF, map to the FMF susceptibility locus (MEFV) on chromosome 16p13.3. We have used informative microsatellite markers flanking this locus to genotype members of the three families mentioned above. Two point and multipoint lod scores definitively excluded linkage to MEFV in the two larger families. A haplotype study confirmed these findings, indicating that FHF is genotypically as well as phenotypically distinct from FMF.

Chromosomes, Human, Pair 16↗