question: What are the puQTLs (promoter-usage Quantitative Trait Loci)?
answer: The identification of genetic variants affecting gene expression, namely expression quantitative trait loci (eQTLs), has contributed to the understanding of mechanisms underlying human traits and diseases. The majority of these variants map in non-coding regulatory regions of the genome and their identification remains challenging. Regulatory variants associated with promoter usage (puQTLs) and enhancer activity (eaQTLs) have been mapped from 154 EBV-transformed lymphoblastoid cell lines, derived from unrelated individuals. There are five categories of genes associated with puQTLs, distinguishing single from multi-promoter genes. Among multi-promoter genes, puQTL effects are either specific to a single promoter or to multiple promoters with variable effect orientations. Regulatory variants associated with opposite effects on different mRNA isoforms suggest compensatory mechanisms occurring between alternative promoters.