- Home
- About
- Collaborative Data Access (SAGs)
- Publications
- For Members
Title | Whole exome sequencing reveals minimal differences between cell line and whole blood derived DNA. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Schafer CM, Campbell NG, Cai G, Yu F, Makarov V, Yoon S, Daly MJ, Gibbs RA, Schellenberg GD, Devlin B, Sutcliffe JS, Buxbaum JD, Roeder K |
Journal | Genomics |
Volume | 102 |
Issue | 4 |
Pagination | 270-7 |
Date Published | 2013 Oct |
ISSN | 1089-8646 |
Keywords | Alleles, Blood Cells, Cell Line, Computational Biology, Exome, Genotype, High-Throughput Nucleotide Sequencing, Humans, Mosaicism, Mutation, Reproducibility of Results, Sequence Analysis, DNA |
Abstract | Two common sources of DNA for whole exome sequencing (WES) are whole blood (WB) and immortalized lymphoblastoid cell line (LCL). However, it is possible that LCLs have a substantially higher rate of mutation than WB, causing concern for their use in sequencing studies. We compared results from paired WB and LCL DNA samples for 16 subjects, using LCLs of low passage number (<5). Using a standard analysis pipeline we detected a large number of discordant genotype calls (approximately 50 per subject) that we segregated into categories of "confidence" based on read-level quality metrics. From these categories and validation by Sanger sequencing, we estimate that the vast majority of the candidate differences were false positives and that our categories were effective in predicting valid sequence differences, including LCLs with putative mosaicism for the non-reference allele (3-4 per exome). These results validate the use of DNA from LCLs of low passage number for exome sequencing. |
DOI | 10.1016/j.ygeno.2013.05.005 |
Alternate Journal | Genomics |
PubMed ID | 23743231 |
PubMed Central ID | PMC3812417 |
Grant List | R01 MH089208 / MH / NIMH NIH HHS / United States R37 MH057881 / MH / NIMH NIH HHS / United States R01 MH089004 / MH / NIMH NIH HHS / United States R01 MH061009 / MH / NIMH NIH HHS / United States P30 HD015052 / HD / NICHD NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States R01MH089175 / MH / NIMH NIH HHS / United States R01 MH057881 / MH / NIMH NIH HHS / United States R01 MH089025 / MH / NIMH NIH HHS / United States R01MH089004 / MH / NIMH NIH HHS / United States R01MH089208 / MH / NIMH NIH HHS / United States R01 MH089175 / MH / NIMH NIH HHS / United States UL1 RR024975 / RR / NCRR NIH HHS / United States R01MH089025 / MH / NIMH NIH HHS / United States T32 GM082773 / GM / NIGMS NIH HHS / United States R01 MH089482 / MH / NIMH NIH HHS / United States |