Haplotype mapping of the bronchiolitis susceptibility locus near IL8.
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.
Hull
Jeremy
J
University Department of Paediatrics, Level 4, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. Jeremy.hull@paediatrics.ox.ac.uk
Rowlands
Kate
K
Lockhart
Elizabeth
E
Sharland
Mike
M
Moore
Catrin
C
Hanchard
Neil
N
Kwiatkowski
Dominic P
DP
D001483:Base Sequence; D001990:Bronchiolitis, Viral / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D005787:Gene Frequency; D005796:Genes; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000235:genetics*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D018357:Respiratory Syncytial Virus Infections / Q000175:diagnosis; D006113:United Kingdom; D044465:White People / Q000235:genetics
D005819:Genetic Markers; D016209:Interleukin-8