The search for candidate genes in asthma and atopy
The search for candidate genes in asthma and atopy
The aim of this study was to develop quantitative phenotype scores for asthma and atopy which maximise heritability avoiding uncertainty over disease definition. Using these scores, markers have been genotyped on chromosome 11q13 within the region containing the β chain of the high affinity IgE receptor (FcεR1-β) and on chromosome 12 as part of the genome scan. A secondary aim was to determine the best method for describing the slope of the bronchial challenge dose-response curve and to compare histamine and AMP bronchial challenges for their ability to predict asthma.
The study population consisted of 131 randomly ascertained families and 109 families recruited via an asthmatic proband.
Phenotype scores were derived using principal component analysis. The asthma score (AS) incorporated written and video questionnaire data reduced to two variables WZ (wheeze) and VID (video), RFEV (the ratio of predicted to observed forced expiratory volume in 1 second) and BHR (the slope of the dose-response curve). Slope was calculated using the equation which best described the data. IGE (log total IgE) was adopted as the atopy score as it showed the highest heritability of the atopy variables. AMP proved superior to histamine in its ability to predict asthma.
The data were analysed using the BETA program for single and multipoint nonparametric linkage analysis. No convincing evidence of linkage was found to FcεR1-β on 11q13 and asthma or atopy. Linkage was found to markers on chromosome 12 and asthma. The largest single-locus lods were achieved for D12S342 and asthma score (lod 2.255), D12S324 and asthma affection (lod 2.214) and D12S366 and wheeze (lod 3.307). The region of interest identified using multipoint analysis, with a maximum lod of 2.29, centres around D12S97 at location 173.5 cM with a standard error of 6.5 for the asthma score and close agreement for asthma affection and wheeze. Future endeavours will be directed towards fine mapping of this region in the hope of identifying novel candidate genes.
University of Southampton
Wilkinson, Jane Elizabeth
1998
Wilkinson, Jane Elizabeth
Wilkinson, Jane Elizabeth
(1998)
The search for candidate genes in asthma and atopy.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The aim of this study was to develop quantitative phenotype scores for asthma and atopy which maximise heritability avoiding uncertainty over disease definition. Using these scores, markers have been genotyped on chromosome 11q13 within the region containing the β chain of the high affinity IgE receptor (FcεR1-β) and on chromosome 12 as part of the genome scan. A secondary aim was to determine the best method for describing the slope of the bronchial challenge dose-response curve and to compare histamine and AMP bronchial challenges for their ability to predict asthma.
The study population consisted of 131 randomly ascertained families and 109 families recruited via an asthmatic proband.
Phenotype scores were derived using principal component analysis. The asthma score (AS) incorporated written and video questionnaire data reduced to two variables WZ (wheeze) and VID (video), RFEV (the ratio of predicted to observed forced expiratory volume in 1 second) and BHR (the slope of the dose-response curve). Slope was calculated using the equation which best described the data. IGE (log total IgE) was adopted as the atopy score as it showed the highest heritability of the atopy variables. AMP proved superior to histamine in its ability to predict asthma.
The data were analysed using the BETA program for single and multipoint nonparametric linkage analysis. No convincing evidence of linkage was found to FcεR1-β on 11q13 and asthma or atopy. Linkage was found to markers on chromosome 12 and asthma. The largest single-locus lods were achieved for D12S342 and asthma score (lod 2.255), D12S324 and asthma affection (lod 2.214) and D12S366 and wheeze (lod 3.307). The region of interest identified using multipoint analysis, with a maximum lod of 2.29, centres around D12S97 at location 173.5 cM with a standard error of 6.5 for the asthma score and close agreement for asthma affection and wheeze. Future endeavours will be directed towards fine mapping of this region in the hope of identifying novel candidate genes.
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Published date: 1998
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Local EPrints ID: 463567
URI: http://eprints.soton.ac.uk/id/eprint/463567
PURE UUID: ca0bd024-f5a2-4b69-82a5-6643c2dd0274
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Date deposited: 04 Jul 2022 20:53
Last modified: 04 Jul 2022 20:53
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Author:
Jane Elizabeth Wilkinson
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