The impact of non-coding genetic variation on promoter function

SCHOR IE

Salta

Congreso; Joint LV Annual SAIB Meeting and XIV PABMB Conference; 2019

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular - Panamerican Association for Biochemistry and Molecular Biology

All known biological species show genetic variation, which accounts for heritable phenotypic differences among the individuals. On the large genomes of metazoans, most of the natural genetic variants occur at non-coding positions. Yet, many of these variants are not neutral, but have the potential to affect gene expression by modifying regulatory elements such as promoters, enhancers or non-coding RNA genes. We have shown that a large proportion of gene promoters that are active during Drosophila embryonic development harbor functional genetic variants that affect transcription. Effects might vary between modulation of start site usage or changes in promoter strength, and their frequency depends on the promoter class. We have also uncovered the presence of cryptic effects of promoter variants on transcriptional noise, which are often alleviated by their genetic context. We are now starting to apply these concepts to characterize the impact of natural promoter variants on gene regulatory networks during mammalian development, as well as the possible role of non-coding somatic mutations on the phenotypic characteristics of cancer cells.