ABSTRACT
Do the over 1,000 individuals cell lines that are part of the 1,000 Human Genomes Project represent a valuable resource for cellular physiology and the importance of genetic variation. For the over 1,000 individuals their genomes were sequenced, and their white blood cells collected, immortalized and cryopreserved. While much research exists on the nucleotide variation in the 1,000 Human Genomes, there are few quantitative measures of these humans’ physiologies. Fortunately, physiological measures can be done on their immortalized and preserved cells. However, these human white blood cells were immortalized by transforming them with the Epstein-Barr virus (EBV-transformed lymphoblastoid cell lines (LCL)). This transformation integrates the viral genome into the human genome and potentially affects important biological differences among individuals. The question we address here is whether this transformation significantly alters the cellular physiology so that replicate individuals are significantly different—that is, does this transformation adds significant level of variance. To investigate the effect of EBV-transformation on the variation among replicate transformation, we quantified oxidative phosphorylation (OxPhos) metabolism in LCLs from six individuals with 4 separate and independent EBV-transformations. We examined OxPhos because it is critical for energy production, and mutations in this pathway are responsible most inborn metabolic diseases. The data presented here demonstrate that there is a small but significant effect of EBV-transformations. In spite of significant variation due to transformation, there is greater and significant variation among individuals in their OxPhos metabolism. Additionally, EBV transformation effects affected specific OxPhos traits: e.g. Complex II, which lacks mtDNA-encoded proteins, may be more sensitive to EBV effects. Inconclusion, while EBV-transformation alters OxPhos, its effect is small and affected specific OxPhos traits and we are able to detect statistically significant variation among individuals.
Footnotes
↵* Contact: dcrawford{at}miami.edu