Fidelity of SNP Array Genotyping Using Epstein Barr Virus-Transformed B-Lymphocyte Cell Lines: Implications for Genome-Wide Association Studies

نویسندگان

  • Joshua T. Herbeck
  • Geoffrey S. Gottlieb
  • Kim Wong
  • Roger Detels
  • John P. Phair
  • Charles R. Rinaldo
  • Lisa P. Jacobson
  • Joseph B. Margolick
  • James I. Mullins
چکیده

BACKGROUND As availability of primary cells can be limited for genetic studies of human disease, lymphoblastoid cell lines (LCL) are common sources of genomic DNA. LCL are created in a transformation process that entails in vitro infection of human B-lymphocytes with the Epstein-Barr Virus (EBV). METHODOLOGY/PRINCIPAL FINDINGS To test for genotypic errors potentially induced by the Epstein-Barr Virus transformation process, we compared single nucleotide polymorphism (SNP) genotype calls in peripheral blood mononuclear cells (PBMC) and LCL from the same individuals. The average mismatch rate across 19 comparisons was 0.12% for SNPs with a population call rate of at least 95%, and 0.03% at SNPs with a call rate of at least 99%. Mismatch rates were not correlated across genotype subarrays run on all sample pairs. CONCLUSIONS/SIGNIFICANCE Genotypic discrepancies found in PBMC and LCL pairs were not significantly different than control pairs, and were not correlated across subarrays. These results suggest that mismatch rates are minimal with stringent quality control, and that most genotypic discrepancies are due to technical artifacts rather than the EBV transformation process. Thus, LCL likely constitute a reliable DNA source for host genotype analysis.

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عنوان ژورنال:

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2009