Mouse to human comparative genetics reveals a novel immunoglobulin E-controlling locus on Hsa8q12

Atopy is a predisposition to hyperproduction of immunoglobulin E (IgE) against common environmental allergens. It is often associated with development of allergic diseases such as asthma, rhinitis, and dermatitis. Production of IgE is influenced by genetic and environmental factors. In spite of progress in the study of heredity of atopy, the genetic mechanisms of IgE regulation have not yet been completely elucidated. The analysis of complex traits can benefit considerably from integration of human and mouse genetics. Previously, we mapped a mouse IgE-controlling locus Lmr9 on chromosome 4 to a segment of <9 Mb. In this study, we tested levels of total IgE and 25 specific IgEs against inhalant and food allergens in 67 Czech atopic families. In the position homologous to Lmr9 on chromosome 8q12 marked by D8S285, we demonstrated a novel human IgE-controlling locus exhibiting suggestive linkage to composite inhalant allergic sensitization (limit of detection, LOD=2.11, P=0.0009) and to nine specific IgEs, with maximum LOD (LOD=2.42, P=0.0004) to plantain. We also tested 16 markers at previously reported chromosomal regions of atopy. Linkage to plant allergens exceeding the LOD>2.0 was detected at 5q33 (D5S1507, LOD=2.11, P=0.0009) and 13q14 (D13S165, LOD=2.74, P=0.0002). The significant association with plant allergens (quantitative and discrete traits) was found at 7p14 (D7S2250, corrected P=0.026) and 12q13 (D12S1298, corrected P=0.043). Thus, the finding of linkage on chromosome 8q12 shows precision and predictive power of mouse models in the investigation of complex traits in humans. Our results also confirm the role of loci at 5q33, 7p14, 12q14, and 13q13 in control of IgE.Impact of genetic and environmental factors on development of atopy and allergic diseases in human population