Association between reduced copy-number at T-cell receptor gamma (TCRb3;) and childhood allergic asthma: A possible role for somatic mosaicism

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• 作者：Kyle M. Walsh ; Michael B. Bracken ; William K. Murk ; Josephine Hoh ; Andrew T. DeWan
• 关键词：T-cell receptor gamma ; Copy-number variant ; Allergic asthma ; Mosaicism
• 刊名：Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
• 出版年：2010
• 出版时间：7 August 2010
• 年：2010
• 卷：690
• 期：1-2
• 页码：89-94
• 全文大小：227 K

文摘

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 TCRb3; and childhood allergic asthma. TCRb3; 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 TCRb1;, TCRb2; or TCRb3; 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 TCRb3; (p = 0.0199), but was not associated at TCRb1; or TCRb2; (p = 0.7972 and 0.8585, respectively). These findings support the association between reduced copy-number at TCRb3; and childhood allergic asthma. Further work is needed to resolve whether reduced copy-number at TCRb3; predisposes individuals to asthma, or whether deletion of this gene is a somatic response to the disease.