Copy number variation and association over T-cell receptor genes--influence of DNA source

Immunogenetics. 2010 Aug;62(8):561-7. doi: 10.1007/s00251-010-0459-7. Epub 2010 Jun 26.


Genomic copy number variants (CNVs) are a common, heritable source of inter-individual differences in genomic sequence. Their influence on phenotypic variability and their involvement in the pathogenesis of several common diseases is well established and the object of many current studies. In the course of examining CNV association to various quantitative traits in a general population, we have detected a strong association of CNVs over the four TCR genes to lymphocyte and neutrophil numbers in blood. In a small replication series, we have further characterized the nature of these CNVs and found them not to be germline, but dependent on the origin of analysed DNA. Germline deletion and rearrangement around the T-cell receptor (TCR) genes naturally occurs in white blood cells. Blood DNA derived from persons with high lymphocyte counts generates variable intensity signals which behave like germline CNVs over these genes. As DNA containing a relative high proportion of these CNV-like events involving the TCR genes has the ability to influence genotype counts of SNPs in the regions of these genes, care should be taken in interpreting and replicating association signals on variants within these genes when blood-derived DNA is the only source of data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cheek
  • DNA / blood
  • DNA / genetics
  • DNA / isolation & purification
  • DNA Copy Number Variations*
  • Genes, T-Cell Receptor*
  • Humans
  • Leukocyte Count
  • Lymphocyte Count
  • Lymphocytes / immunology
  • Models, Genetic
  • Mouth Mucosa / metabolism
  • Neutrophils / immunology
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Quantitative Trait, Heritable
  • Sequence Deletion


  • DNA