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Am. J. Respir. Crit. Care Med., Volume 156, Number 4, October 1997, S144-S151

The Candidate Region Approach to the Genetics of Asthma and Allergy

N. S. THOMAS, J. WILKINSON, and S. T. HOLGATE

Southampton General Hospital, Southampton, United Kingdom

To date, the strongest linkage claims for genes underlying asthma and atopy have been for chromosomes 5 and 11. Chromosome 5q contains the cytokine cluster and the beta 2 adrenoceptor, and the beta  chain of the high-affinity IgE receptor (Fcepsilon RI-beta ) is encoded on chromosome 11q13. We have attempted to replicate these findings in two distinct sample populations from the United Kingdom. Allelic associations were identified in both regions, but there was no significant evidence for linkage. Although we could not substantiate the existence of the nucleotide changes reported within exon 6 of the Fcepsilon RI-beta gene, an amino acid substitution in exon 7 was strongly linked to asthma and atopy. We have also identified positive linkage and allelic associations to several markers on chromosome 12q in both our UK populations. Independent evidence from another study also supports linkage to 12q, so although our data could not confirm linkage to chromosomes 5 or 11, we have identified an additional region of the genome that could be important for the genetic predisposition to asthma and atopy. Thomas NS, Wilkinson J, Holgate ST. The candidate region approach to the genetics of asthma and allergy.




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