Cell line donor genotype and its influence on experimental phenotype: Toll-like receptor SNPs and potential variability in innate immunity

Cell lines are used to model a disease and provide valuable information regarding phenotype, mechanism, and response to novel therapies. Derived from individuals of diverse genetic backgrounds, the cell's genetic complement predicts the phenotype, and although some lines have been sequenced, little emphasis has been placed on genotyping. Toll-like receptors (TLRs) are essential in initiating the inflammatory cascade in response to infection. TLR single nucleotide polymorphism (SNP) alleles may predict an altered innate immune response: a SNP can affect TLR-dependent pathways and may alter experimental results. Thus, genotype variation may have far-reaching implications when using cell lines to model phenotypes. We recommend that cell lines be genotyped and cataloged in a fashion similar to that used for bacteria, with cumulative information being archived in an accessible central database to facilitate the understanding of SNP cell phenotypes reported in the literature.