atopy, specific IgE, genetic loci; mouse–human homology, 8q12; Czech population
Abstract :
[en] 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Gusareva, Elena ; Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique
Havelková, Helena; Institute of Molecular Genetics, Prague, Chzech Republic > Molecular and Cellular Immunology
Blažková, Hana; Institute of Molecular Genetics, Prague, Chzech Republic > Molecular and Cellular Immunology
Kosařová, Marcela; Institute of Molecular Genetics, Prague, Chzech Republic > Molecular and Cellular Immunology
Language :
English
Title :
Mouse to human comparative genetics reveals a novel immunoglobulin E-controlling locus on Hsa8q12
Publication date :
January 2009
Journal title :
Immunogenetics
ISSN :
0093-7711
eISSN :
1432-1211
Publisher :
Springer, Germany
Volume :
61
Issue :
1
Pages :
15-25
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Impact of genetic and environmental factors on development of atopy and allergic diseases in human populations
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