Publications
396 results found
Cookson W, Moffatt M, 2002, Immunological and genetic mechanisms of asthma, Annales Nestle, Vol: 60, Pages: 56-65, ISSN: 0517-8606
Zhang Y, Cookson W, 2002, Case study of QTL analysis in a mouse model of asthma., Quantitative Trait Loci: Methods and Protocols, Editors: Camp, Cox, Publisher: Springer, Pages: 253-279, ISBN: 978-0-89603-927-8
Asthma is the most common childhood disease. It is characterized by inflammation of the small airways of the lung that produces intermittent narrowing of the respiratory bronchioles, airflow limitation, and the symptoms of wheezing, chest tightness, and breathless ness. The most common form is allergic asthma, also known as atopic asthma. The atopic state is distinguished by the strength of the immunoglobulin E (IgE) response to commonly inhaled proteins, known as allergens.
Willis-Owen SA, 2002, Asthma: Genetics., Encyclopedia of Life Sciences (ELS)., Chichester, Publisher: John Wiley & Sons, Ltd
Abecasis GR, Cherny SS, Cookson WO, et al., 2002, Merlin-rapid analysis of dense genetic maps using sparse gene flow trees, NATURE GENETICS, Vol: 30, Pages: 97-101, ISSN: 1061-4036
- Author Web Link
- Cite
- Citations: 2743
Boulet JR, McKinley DW, Norcini JJ, et al., 2002, Assessing the comparability of standardized patient and physician evaluations of clinical skills., Adv Health Sci Educ Theory Pract, Vol: 7, Pages: 85-97, ISSN: 1382-4996
Accumulating evidence to defend decisions based on scores from evaluations is an ongoing process. The purpose of this investigation was to gather additional data to support the validity of inferences made from scores on the Educational Commission for Foreign Medical Graduates' Clinical Skills Assessment (CSA). This was accomplished by contrasting CSA candidate scores, and pass/fail decisions, with those obtained from the American Board of Internal Medicine's Mini-CEX (Clinical Evaluation Exercise). Data gathering performance based on the number of unweighted history taking and physical examination checklist items adequately predicted the global ratings provided by physician observers. CSA ratings of doctor-patient communication skills correlated with mini-CEX ratings of like constructs, indicating that physician observers, using mini-CEX rating scales, are able to make realistic assessments of interpersonal skills. These results provide evidence of the convergent validity of CSA scores.
Bracken MB, Belanger K, Cookson WO, et al., 2002, Genetic and perinatal risk factors for asthma onset and severity: A review and theoretical analysis, EPIDEMIOLOGIC REVIEWS, Vol: 24, Pages: 176-189, ISSN: 0193-936X
- Author Web Link
- Cite
- Citations: 51
Walley AJ, Chavanas S, Moffatt ME, et al., 2001, Gene polymorphism in Netherton and common atopic disease, NATURE GENETICS, Vol: 29, Pages: 175-178, ISSN: 1061-4036
- Author Web Link
- Cite
- Citations: 288
Abecasis GR, Cherny SS, Cookson WO, et al., 2001, GRR: graphical representation of relationship errors., Bioinformatics, Vol: 17, Pages: 742-743, ISSN: 1367-4803
SUMMARY: A graphical tool for verifying assumed relationships between individuals in genetic studies is described. GRR can detect many common errors using genotypes from many markers. AVAILABILITY: GRR is available at http://bioinformatics.well.ox.ac.uk/GRR.
Abecasis GR, Cookson WO, Cardon LR, 2001, The power to detect linkage disequilibrium with quantitative traits in selected samples., Am J Hum Genet, Vol: 68, Pages: 1463-1474, ISSN: 0002-9297
Results from power studies for linkage detection have led to many ongoing and planned collections of phenotypically extreme nuclear families. Given the great expense of collecting these families and the imminent availability of a dense diallelic marker map, the families are likely to be used in allelic-association as well as linkage studies. However, optimal selection strategies for linkage may not be equally powerful for association. We examine the power to detect linkage disequilibrium for quantitative traits after phenotypic selection. The results encompass six selection strategies that are in widespread use, including single selection (two designs), affected sib pairs, concordant and discordant pairs, and the extreme-concordant and -discordant design. Selection of sibships on the basis of one extreme proband with high or low trait scores provides as much power as discordant sib pairs but requires the screening and phenotyping of substantially fewer initial families from which to select. Analysis of the role of allele frequencies within each selection design indicates that common trait alleles generally offer the most power, but similarities between the marker- and trait-allele frequencies are much more important than the trait-locus frequency alone. Some of the most widespread selection designs, such as single selection, yield power gains only when both the marker and quantitative trait loci (QTL) are relatively rare in the population. In contrast, discordant pairs and the extreme-proband design provide power for the broadest range of QTL-marker-allele frequency differences. Overall, proband selection from either tail provides the best balance of power, robustness, and simplicity of ascertainment for family-based association analysis.
Moffatt MF, Schou C, Faux JA, et al., 2001, Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample, EUROPEAN JOURNAL OF HUMAN GENETICS, Vol: 9, Pages: 341-346, ISSN: 1018-4813
- Author Web Link
- Cite
- Citations: 60
Palmer LJ, Barnes KC, Burton PR, et al., 2001, Meta-analysis for linkage to asthma and atopy in the chromosome 5q31-33 candidate region, HUMAN MOLECULAR GENETICS, Vol: 10, Pages: 891-899, ISSN: 0964-6906
- Author Web Link
- Cite
- Citations: 15
Palmer LJ, Cookson WOCM, James AL, et al., 2001, Gibbs sampling-based segregation analysis of asthma-associated quantitative traits in a population-based sample of nuclear families, GENETIC EPIDEMIOLOGY, Vol: 20, Pages: 356-372, ISSN: 0741-0395
- Author Web Link
- Cite
- Citations: 25
Cookson WO, Ubhi B, Lawrence R, et al., 2001, Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci., Nat Genet, Vol: 27, Pages: 372-373, ISSN: 1061-4036
We have carried out a genome screen for atopic dermatitis (AD) and have identified linkage to AD on chromosomes 1q21, 17q25 and 20p. These regions correspond closely with known psoriasis loci, as does a previously identified AD locus on chromosome 3q21. The results indicate that AD is influenced by genes with general effects on dermal inflammation and immunity.
Godfrey S, 2001, Independent inheritance of serum immunoglobulin E concentrations and airway responsiveness., Am J Respir Crit Care Med, Vol: 163, ISSN: 1073-449X
Palmer LJ, Lonjou C, Barnes K, et al., 2001, A retrospective collaboration on chromosome 5 by the International Consortium on Asthma Genetics (COAG), Clinical and Experimental Allergy, Vol: 31, Pages: 152-154, ISSN: 0954-7894
- Cite
- Citations: 10
Walley AJ, Wiltshire S, Ellis CM, et al., 2001, Linkage and allelic association of chromosome 5 cytokine cluster genetic markers with atopy and asthma associated traits, GENOMICS, Vol: 72, Pages: 15-20, ISSN: 0888-7543
- Author Web Link
- Cite
- Citations: 56
Abecasis GR, Noguchi E, Heinzmann A, et al., 2001, Extent and Distribution of Linkage Disequilibrium in Three Genomic Regions., American Journal of Human Genetics, Vol: 68, Pages: 191-197, ISSN: 0002-9297
The positional cloning of genes underlying common complex diseases relies on the identification of linkage disequilibrium (LD) between genetic markers and disease. We have examined 127 polymorphisms in three genomic regions in a sample of 575 chromosomes from unrelated individuals of British ancestry. To establish phase, 800 individuals were genotyped in 160 families. The fine structure of LD was found to be highly irregular. Forty-five percent of the variation in disequilibrium measures could be explained by physical distance. Additional factors, such as allele frequency, type of polymorphism, and genomic location, explained <5% of the variation. Nevertheless, disequilibrium was occasionally detectable at 500 kb and was present for over one-half of marker pairs separated by <50 kb. Although these findings are encouraging for the prospects of a genomewide LD map, they suggest caution in interpreting localization due to allelic association.
Cookson WOCM, Abeçasis GR, 2001, Oxford genome screen for asthma-associated traits, ISSN: 0741-0395
A genome screen for linkage of quantitative traits underlying asthma has been carried out previously by our group on 80 families sub-selected for discordant phenotypes from a general population sample. The families contained a total of 203 offspring forming 172 sib-pairs. Genotypic data for at a total of 296 markers were available. This paper describes the ascertainment, phenotypic data, and genotypic data made available for Genetic Analysis Workshop 12. © 2001 Wiley-Liss, Inc.
Cherny SS, Abecasis GR, Cookson WOC, et al., 2001, The effect of genotype and pedigree error on linkage analysis: Analysis of three asthma genome scans, ISSN: 0741-0395
The effects of genotype and relationship errors on linkage results are evaluated in three of the Genetic Analysis Workshop 12 asthma genome scans. A number of errors are detected in the samples. While the evidence for linkage is not striking in any data set with or without error, in some cases the difference in test statistic could support different conclusions. The results provide empirical evidence for the predicted effects of genotype and relationship error and highlight the need for rigorous detection and elimination of data error in complex trait studies. © 2001 Wiley-Liss, Inc.
Palmer LJ, Cookson WOCM, Deichmann KA, et al., 2001, Single region linkage analyses of asthma: Description of data sets, ISSN: 0741-0395
Linkage (genotypic) data from the 5q31-33 candidate region for asthma were contributed to Genetic Analysis Workshop 12 by members of the International Consortium on Asthma Genetics (COAG). Data came from five independent studies sampled from five countries. Genotypic data for a total of 26 markers were available, although the number of markers typed in each data set varied. Phenotypic and genotypic data was available from a total of 569 families and 3,175 subjects. The phenotypic data available varied among the studies; however information regarding physician-diagnosed asthma and total serum IgE levels was available in all five studies. This paper describes the ascertainment, data collection methods, phenotypic data, and genotypic data available for the single linkage region analyses undertaken for Genetic Analysis Workshop 12. © 2001 Wiley-Liss, Inc.
Abecasis GR, Cardon LR, Cookson WOC, et al., 2001, Association analysis in a variance components framework, ISSN: 0741-0395
Association analyses conducted in a variance components framework can include information from all available individuals but remain unbiased in the presence of familiality or linkage. Models that include both linkage and association parameters provide different estimates of the effect of a single locus and can be used to distinguish causal polymorphisms from other types of variation. We examine some of these models and their properties in a blind analysis of the simulated Genetic Analysis Workshop 12 data sets. © 2001 Wiley-Liss, Inc.
Cherny SS, Abecasis GR, Cookson WOC, et al., 2001, The effect of genotype and pedigree error on linkage analysis: Analysis of three asthma genome scans, GENETIC EPIDEMIOLOGY, Vol: 21, Pages: S117-S122, ISSN: 0741-0395
- Author Web Link
- Cite
- Citations: 18
Bhattacharyya S, Leaves NI, Wiltshire S, et al., 2000, A high-density genetic map of the chromosome 13q14 atopy locus, GENOMICS, Vol: 70, Pages: 286-291, ISSN: 0888-7543
- Author Web Link
- Cite
- Citations: 11
Palmer LJ, Burton PR, James AL, et al., 2000, Familial aggregation and heritability of asthma-associated quantitative traits in a population-based sample of nuclear families., Eur J Hum Genet, Vol: 8, Pages: 853-860, ISSN: 1018-4813
Asthma is a common, genetically complex human disease. Elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts, variably reduced spirometric measures and increased airway responsiveness (AR) are physiological traits which are characteristic of asthma. We investigated the genetic and environmental components of variance of serum total and specific IgE levels, blood eosinophil counts, the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and AR in an Australian population-based sample of 232 Caucasian nuclear families. With the exception of FVC levels, all traits were closely associated with clinical asthma in this population. Loge total serum IgE levels had a narrow-sense heritability (h2N) of 47.3% (SE = 10. 0%). Specific serum IgE levels against house dust mite and Timothy grass, measured as a RAST Index, had a h2N of 33.8% (SE = 7.3%). FEV1 levels had a h2N of 6.1% (SE = 11.6%), whilst FVC levels had a h2N of 30.6% (SE = 26.8%). AR, quantified by the loge dose-response slope to methacholine (DRS), had a h2N of 30.3% (SE = 12.3%). These data are consistent with the existence of important genetic determinants of the pathophysiological traits associated with asthma. Our study suggests that total and specific serum IgE levels, blood eosinophil counts and airways responsiveness to inhaled agonist are appropriate phenotypes for molecular investigations of the genetic susceptibility to asthma.
Kurz T, Strauch K, Heinzmann A, et al., 2000, A European study on the genetics of mite sensitization, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 106, Pages: 925-932, ISSN: 0091-6749
- Author Web Link
- Cite
- Citations: 41
Mitchell TJ, Walley AJ, Pease JE, et al., 2000, Delta 32 deletion of CCR5 gene and association with asthma or atopy, LANCET, Vol: 356, Pages: 1491-1492, ISSN: 0140-6736
- Author Web Link
- Cite
- Citations: 39
Donnadieu E, Cookson WO, Jouvin MH, et al., 2000, Allergy-associated polymorphisms of the Fc epsilon RI beta subunit do not impact its two amplification functions., J Immunol, Vol: 165, Pages: 3917-3922, ISSN: 0022-1767
Two variants of the beta-chain of the high affinity IgE receptor Fc epsilon RI, I181L-V183L and E237G, have been found associated with allergy. We have previously shown that the beta-chain plays at least two distinct amplifier functions. It amplifies Fc epsilon RI surface expression and signaling, resulting in an estimated 12- to 30-fold amplification of downstream events. To test the hypothesis that the I181L-V183L and E237G beta variants may be functionally relevant and could directly contribute to an allergic phenotype, we have evaluated the functional impact of the beta variants on the two amplifier functions of beta. We found that these variants have no direct effect on the beta amplifier functions. However, the possibility remains that these variants are in linkage disequilibrium with other more relevant polymorphisms or are affecting unknown beta-chain functions.
Cookson WO, Moffatt MF, 2000, Genetics of asthma and allergic disease., Hum Mol Genet, Vol: 9, Pages: 2359-2364, ISSN: 0964-6906
Atopic (allergic) asthma is the most common disease of childhood and is strongly genetic in origin. Many genome-wide screens for asthma and its associated traits have now been carried out, and genetic linkage has been consistently identified in several regions. It is probable that these loci contain major genes influencing atopy and asthma. Candidate genes have already been identified from the cytokine cluster on chromosome 5 and the MHC on chromosome 6. These complex regions contain more than one susceptibility locus for allergic disease. Other regions do not contain obvious candidate genes, and positional cloning of these loci is likely to identify novel disease pathways. Parent-of-origin effects are prominent at some of the loci and some also show linkage to other inflammatory immune diseases. Several single gene disorders are associated with allergic disease and on occasion are also linked to the same chromosomal regions. The positional cloning of asthma genes is now feasible.
Lonjou C, Barnes K, Chen H, et al., 2000, A first trial of retrospective collaboration for positional cloning in complex inheritance: Assay of the cytokine region on chromosome 5 by the Consortium on Asthma Genetics (COAG), Proceedings of the National Academy of Sciences of the United States of America, Vol: 97, Pages: 10942-10947, ISSN: 0027-8424
The central problem of complex inheritance is to map oligogenes for disease susceptibility, integrating linkage and association over samples that differ in several ways. Combination of evidence over multiple samples with 1,037 families supports loci contributing to asthma susceptibility in the cytokine region on 5q [maximum logarithm of odds (lod) = 2.61 near IL-4], but no evidence for atopy. The principal problems with retrospective collaboration on linkage appear to have been solved, providing far more information than a single study. A multipoint lod table evaluated at commonly agreed reference loci is required for both collaboration and metaanalysis, but variations in ascertainment, pedigree structure, phenotype definition, and marker selection are tolerated. These methods are invariant with statistical methods that increase the power of lods and are applicable to all diseases, motivating collaboration rather than competition. In contrast to linkage, positional cloning by allelic association has yet to be extended to multiple samples, a prerequisite for efficient combination with linkage and the greatest current challenge to genetic epidemiology.
Palmer LJ, Cookson WO, 2000, Genomic approaches to understanding asthma., Genome Res, Vol: 10, Pages: 1280-1287, ISSN: 1088-9051
Asthma is the most common chronic childhood disease in developed nations, and it is a complex disease that has high social and economic costs. Asthma and its associated intermediate phenotypes are under a substantial degree of genetic control. The genetic aetiology of asthma offers a means of better understanding its pathogenesis and, thus, improving preventive strategies, diagnostic tools, and therapies. Considerable effort and expense have been expended in attempts to detect genetic loci contributing to asthma susceptibility, and extensive candidate gene studies and a number of whole-genome screens have been undertaken. This article reviews the current state of knowledge of the genetics of asthma, with a focus on genomic approaches to understanding allergic diseases.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.