Physical map of an asthma susceptibility locus in 7p15-p14 and an association study of TCRG

Abstract

Chromosome 7p15-p14 showed genome-wide significant linkage to asthma related traits among the Finnish and French-Canadian families. As an essential step toward cloning the susceptibility gene, a detailed physical map of the region is needed. In this study we report a dense set of carefully tested, new microsatellite markers for fine mapping embedded in a continuous, easy-to-read, physical map of the region that includes the known genes and putative transcripts. Even though susceptibility genes for asthma are difficult to predict from a multitude of unknown genes mapped to the region, TCRG encoding the γ-chain of the heteroclimeric γ/δ T cell receptor is a potential candidate. We present linkage and association results for TCRG in two independent Finnish family sets by using four highly polymorphic microsatellites spanning 169 kb across the locus. Linkage results confirmed our previous findings, but our study did not provide any evidence on behalf of a strong association of TCRG with either high serum total Immunoglobulin (IgE) level or asthma. Our results suggest that some other known or yet unidentified gene in the linkage region is the true asthma susceptibility gene.