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Chunk #0 — INTRODUCTION

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Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles.
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Defining the genetic determinants of gene expression is crucial to understanding the biological and medical significance of genetic variation. This has particular relevance in the drive to identify functional variants underlying observed disease associations from genome-wide association studies (GWAS)1. It is increasingly apparent that functional activity of many genetic polymorphisms is dependent upon context, requiring the study of relevant cell or tissue types in a particular biological state2-4. This context-specificity means that whilst lymphoblastoid cell lines (LCLs) and other tissues have provided important insights, they may fail to capture the in vivo activity of particular variants in disease relevant tissues5,6. Recent cell and tissue specific studies highlight the importance of context in the identification of expression associated genetic variants3,4,7-10. In umbilical cord-derived cultured cells, up to 80% of regulatory variants act in a cell-type specific manner3, whilst comparison of skin, fat and LCLs identify only 30% of eQTLs to be common between tissues4. The basis for this specificity remains unresolved, but may relate to variation at tissue specific distal enhancers as opposed to conserved promoter elements3. Analyses performed on non-cultured