title: Association between reduced copy-number at T-cell receptor gamma (TCRgamma) and childhood allergic asthma: A possible role for somatic mosaicism.
abstract: Asthma is a chronic inflammatory disease of the lungs which affects more than 6.5 million American children. A family-based genome-wide association study of copy-number variation identified an association between decreased copy-number at TCRgamma and childhood allergic asthma. TCRgamma encodes the T-cell receptor gamma glycoprotein, a cell-surface protein found on T-cells and involved in cell-mediated immunity. Using quantitative real-time PCR, we sought to determine if copy-number variation at TCRalpha, TCRbeta or TCRgamma was associated with childhood allergic asthma in an independent cohort of 94 cases and 455 controls using DNA from buccal swabs. Copy-number variation at these loci is well-known, but appears to be dominated by somatic mutations. Genotyping results indicated that copy-number variants at these genes are largely somatic mutations, as inheritance did not show Mendelian consistency. In these mosaic cell populations, copy-number was significantly reduced among asthmatic children at TCRgamma (p=0.0199), but was not associated at TCRalpha or TCRbeta (p=0.7972 and 0.8585, respectively). These findings support the association between reduced copy-number at TCRgamma and childhood allergic asthma. Further work is needed to resolve whether reduced copy-number at TCRgamma predisposes individuals to asthma, or whether deletion of this gene is a somatic response to the disease.
authors.affiliation: Center for Perinatal Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, CT 06510, USA.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Walsh
authors.forename: Michael B
authors.initials: MB
authors.lastname: Bracken
authors.forename: William K
authors.initials: WK
authors.lastname: Murk
authors.forename: Josephine
authors.initials: J
authors.lastname: Hoh
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Dewan
mesh_terms: D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D056915:DNA Copy Number Variations; D005260:Female; D019675:Genes, T-Cell Receptor gamma; D006801:Humans; D007223:Infant; D008297:Male; D009030:Mosaicism