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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Walsh, KM; Bracken, MB; Murk, WK; Hoh, J; Dewan, AT

Published Date

  • August 7, 2010

Published In

Volume / Issue

  • 690 / 1-2

Start / End Page

  • 89 - 94

PubMed ID

  • 20553737

Pubmed Central ID

  • 20553737

International Standard Serial Number (ISSN)

  • 0027-5107

Digital Object Identifier (DOI)

  • 10.1016/j.mrfmmm.2010.05.005


  • eng

Conference Location

  • Netherlands