Project Details
Projekt
Contribution of genetic risk variation in G-quadruplex regions to COVID-19 and other complex genetics traits
Subject Area
Human Genetics
Biochemistry
Biochemistry
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 544278214
Advances in genomics technology and collaborative efforts have significantly enhanced our ability to identify human genetic variations that contribute to disease risk. However, our understanding of how these variants functionally affect human traits hasn't kept pace with the increasing number of identified candidate variants. This is particularly true for the non-coding genome, which constitutes over 98% of the genomic space and contains variants associated with common traits and a yet unknown number of monogenic disorders. Recent discoveries of novel disease mechanisms have underscored the potential of interdisciplinary collaborations among biochemistry, cell biology and human genetics, for the identification of novel functional effects of risk variants. Variants in non-coding regions, including single-nucleotide variants (SNVs), are thought to influence human traits and diseases by altering the regulation of transcriptional programs in terms of their spatial and temporal control. While much of the research has focused on the standard B-DNA conformation, the genome can also adopt non-canonical (non-B) DNA structures, such as guanine quadruplex (G4) structures. These non-B structures may carry biological information beyond the primary sequence. Although the impact of somatic mutations on non-B-DNA has been explored in cancer, the effect of inherited (germline) SNVs on G4 formation has received limited attention. This project aims to explore common disease-associated SNVs within the context of non-canonical DNA structures, particularly G4s, which are prevalent in non-coding genomic regions. The hypothesis posits that genetic variations within sequences with G4-forming potential contribute to the development of multifactorial traits. Specifically, it suggests that disease-associated SNVs can (i) directly affect G4 formation and (ii) modify G4-mediated transcription and translation in specific contexts.
DFG Programme
Research Grants
