TY - JOUR
T1 - Fidelity of SNP array genotyping using Epstein Barr virus-transformed B-lymphocyte cell lines
T2 - Implications for genome-wide association studies
AU - Herbeck, Joshua T.
AU - Gottlieb, Geoffrey S.
AU - Wong, Kim
AU - Detels, Roger
AU - Phair, John P.
AU - Rinaldo, Charles R.
AU - Jacobson, Lisa P.
AU - Margolick, Joseph B.
AU - Mullins, James I.
PY - 2009/9/4
Y1 - 2009/9/4
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0006915
DO - 10.1371/journal.pone.0006915
M3 - Article
C2 - 19730697
AN - SCOPUS:70149113719
SN - 1932-6203
VL - 4
JO - PloS one
JF - PloS one
IS - 9
M1 - e6915
ER -