BACKGROUND: Allergic diseases such as asthma and rhinitis have closely related phenotypes and often occur with atopy. They show strong familial and intra-individual clustering, suggesting overlapping disease aetiology. Various loci and candidate genes have been suggested to underlie allergy. Many or all are still inconclusive. Following genome-wide scans on multiple phenotypes, we previously suggested that chromosome 3q13.12-q21.2 harbours an allergy locus. OBJECTIVE: To identify candidate loci in the Danish population, two additional independent sets of sib-pair families were fine-scale mapped in candidate regions showing maximum likelihood scores (MLS) > or =1.5 in the genome-wide scans. RESULTS: Twenty eight microsatellite markers in a denser map on chromosome 3q were analysed in 236 allergy sib-pair families including 125 sib pairs with rhinitis. We report significant evidence for linkage to chromosome 3q13.31 for rhinitis (MLS 5.55, identity by descent (IBD) 63.9%) and atopy (increased specific immunoglobulin E) (MLS 3.71, IBD 61.7%). We obtained an MLS of 5.1 (IBD 67.3%) at 3q13.31 when sib pairs with both rhinitis and atopy were analysed. CONCLUSION: This study reports the first statistically significant evidence for a genetic susceptibility locus for rhinitis and to our knowledge shows the most significant evidence to date of linkage for any allergy phenotype.
BACKGROUND:Allergic diseases such as asthma and rhinitis have closely related phenotypes and often occur with atopy. They show strong familial and intra-individual clustering, suggesting overlapping disease aetiology. Various loci and candidate genes have been suggested to underlie allergy. Many or all are still inconclusive. Following genome-wide scans on multiple phenotypes, we previously suggested that chromosome 3q13.12-q21.2 harbours an allergy locus. OBJECTIVE: To identify candidate loci in the Danish population, two additional independent sets of sib-pair families were fine-scale mapped in candidate regions showing maximum likelihood scores (MLS) > or =1.5 in the genome-wide scans. RESULTS: Twenty eight microsatellite markers in a denser map on chromosome 3q were analysed in 236 allergy sib-pair families including 125 sib pairs with rhinitis. We report significant evidence for linkage to chromosome 3q13.31 for rhinitis (MLS 5.55, identity by descent (IBD) 63.9%) and atopy (increased specific immunoglobulin E) (MLS 3.71, IBD 61.7%). We obtained an MLS of 5.1 (IBD 67.3%) at 3q13.31 when sib pairs with both rhinitis and atopy were analysed. CONCLUSION: This study reports the first statistically significant evidence for a genetic susceptibility locus for rhinitis and to our knowledge shows the most significant evidence to date of linkage for any allergy phenotype.
Authors: T Laitinen; M J Daly; J D Rioux; P Kauppi; C Laprise; T Petäys; T Green; M Cargill; T Haahtela; E S Lander; L A Laitinen; T J Hudson; J Kere Journal: Nat Genet Date: 2001-05 Impact factor: 38.330
Authors: Y A Lee; U Wahn; R Kehrt; L Tarani; L Businco; D Gustafsson; F Andersson; A P Oranje; A Wolkertstorfer; A v Berg; U Hoffmann; W Küster; T Wienker; F Rüschendorf; A Reis Journal: Nat Genet Date: 2000-12 Impact factor: 38.330
Authors: Y Yokouchi; M Shibasaki; E Noguchi; J Nakayama; T Ohtsuki; M Kamioka; K Yamakawa-Kobayashi; S Ito; K Takeda; K Ichikawa; Y Nukaga; A Matsui; H Hamaguchi; T Arinami Journal: Genes Immun Date: 2002-02 Impact factor: 2.676
Authors: Simon P Hogan; Luqman Seidu; Carine Blanchard; Katherine Groschwitz; Anil Mishra; Margaret L Karow; Richard Ahrens; David Artis; Andrew J Murphy; David M Valenzuela; George D Yancopoulos; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2006-07 Impact factor: 10.793
Authors: Tianju Liu; Hyun Ah Baek; Hongfeng Yu; Ho Jin Lee; Byung-Hyun Park; Matthew Ullenbruch; Jianhua Liu; Taku Nakashima; Yoon Young Choi; Gary D Wu; Myoung Ja Chung; Sem H Phan Journal: J Immunol Date: 2011-05-20 Impact factor: 5.422