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Haplotype mapping of the bronchiolitis susceptibility locus near<Emphasis Type="Italic"> IL8</Emphasis>
Authors:Email author" target="_blank">Jeremy?HullEmail author  Kate?Rowlands  Elizabeth?Lockhart  Mike?Sharland  Catrin?Moore  Neil?Hanchard  Dominic?P?Kwiatkowski
Institution:(1) University Department of Paediatrics, Level 4, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK;(2) Paediatric Infectious Diseases Unit, St Georges Hospital, London, UK;(3) Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK;(4) Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Abstract:Susceptibility to viral bronchiolitis, the commonest cause of infant admissions to hospital in the industrialised world, is associated with polymorphism at the IL8 locus. Here we map the genomic boundaries of the disease association by case-control analysis and TDT in 580 affected UK infants. Markers for association mapping were chosen after determining patterns of linkage disequilibium across the surrounding region of chromosome 4q, a 550-kb segment containing nine genes, extending from AFP to PPBP. The region has three major clusters of high linkage disequilibrium and is notable for its low haplotypic diversity. We exclude adjacent chemokine genes as the cause of the association, and identify a disease-associated haplotype that spans a 250-kb region from AFM to IL8. In between these two genes there is only one structural feature of interest, a novel gene RASSF6, which is predicted to encode a Ras effector protein.
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