UNIGE document Scientific Article
previous document  unige:19015  next document
add to browser collection

Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines

Choy, Edwin
Yelensky, Roman
Bonakdar, Sasha
Plenge, Robert M.
Saxena, Richa
De Jager, Philip L.
Shaw, Stanley Y.
Wolfish, Cara S.
show hidden authors show all authors [1 - 17]
Published in PLOS Genetics. 2008, vol. 4, no. 11, p. e1000287
Abstract Lymphoblastoid cell lines (LCLs), originally collected as renewable sources of DNA, are now being used as a model system to study genotype-phenotype relationships in human cells, including searches for QTLs influencing levels of individual mRNAs and responses to drugs and radiation. In the course of attempting to map genes for drug response using 269 LCLs from the International HapMap Project, we evaluated the extent to which biological noise and non-genetic confounders contribute to trait variability in LCLs. While drug responses could be technically well measured on a given day, we observed significant day-to-day variability and substantial correlation to non-genetic confounders, such as baseline growth rates and metabolic state in culture. After correcting for these confounders, we were unable to detect any QTLs with genome-wide significance for drug response. A much higher proportion of variance in mRNA levels may be attributed to non-genetic factors (intra-individual variance--i.e., biological noise, levels of the EBV virus used to transform the cells, ATP levels) than to detectable eQTLs. Finally, in an attempt to improve power, we focused analysis on those genes that had both detectable eQTLs and correlation to drug response; we were unable to detect evidence that eQTL SNPs are convincingly associated with drug response in the model. While LCLs are a promising model for pharmacogenetic experiments, biological noise and in vitro artifacts may reduce power and have the potential to create spurious association due to confounding.
Keywords Cell LineDNA, Mitochondrial/genetics/metabolismDrug Resistance/genetics/immunologyGene Expression ProfilingGenetic VariationHerpesvirus 4, Human/genetics/immunologyHumansLymphocytes/*drug effects/*metabolismPhenotype*Quantitative Trait LociRNA, Messenger/*metabolism
PMID: 19043577
Full text
Research group Population Genomics and Genetics of Complex Traits (892)
(ISO format)
CHOY, Edwin et al. Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines. In: PLOS Genetics, 2008, vol. 4, n° 11, p. e1000287. https://archive-ouverte.unige.ch/unige:19015

112 hits



Deposited on : 2012-03-27

Export document
Format :
Citation style :