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 disequilibrium 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.

Original publication

DOI

10.1007/s00439-003-1038-x

Type

Journal article

Journal

Human genetics

Publication Date

02/2004

Volume

114

Pages

272 - 279

Addresses

University Department of Paediatrics, Level 4, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. Jeremy.hull@paediatrics.ox.ac.uk

Keywords

Chromosomes, Human, Pair 4, Humans, Bronchiolitis, Viral, Respiratory Syncytial Virus Infections, Genetic Predisposition to Disease, Interleukin-8, Genetic Markers, Case-Control Studies, Chromosome Mapping, Base Sequence, Gene Frequency, Haplotypes, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Genes, Infant, European Continental Ancestry Group, United Kingdom