Association between reduced copy-number at T-cell receptor gamma (TCRγ) and childhood allergic asthma: A possible role for somatic mosaicism

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 TCR gamma and childhood allergic asthma. TCR gamma 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 TCR alpha, TCR beta or TCR gamma 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 TCR gamma (p = 0.0199). but was not associated at TCR alpha or TCR beta (p = 0.7972 and 0.8585, respectively). These findings support the association between reduced copy-number at TCR gamma and childhood allergic asthma. Further work is needed to resolve whether reduced copy-number at TCR gamma predisposes individuals to asthma, or whether kdeletion of this gene is a somatic response to the disease. (C) 2010 Elsevier B.V. All rights reserved.