Objective Mutational processes that generate structural variants (SV) in human and other genomes are understudied and merit attention, and similarly so for the functional impact of the SVs on gene function and regulation. SVs may explain some of the missing heritability in population studies, they may provide candidate pathogenic variants in pedigree studies of hereditary diseases, as well as constitute yet-undiscovered driver events that were anticipated from cancer genomics. Reasons why the SV mutational processes and SV functional impact are understudied are both of a technical and a conceptual nature; both aspects will be addressed in the STRUCTOMATIC project. We will study structural variation in human somatic cells by combining diverse computational and experimental approaches, drawing on a genomic resource of hundreds of tumors and healthy tissues sequenced using long-read WGS that we will generate. We will further perform mutation accumulation and directed evolution experiments using cell line models of chromosomal instability, generating further genomic data that will support observational analyses of tumor genomes. The project aims are: thoroughly cataloguing the diversity of SVs in multiple somatic cell types including those not detectable by short-read WGS, elucidating the underlying mutational mechanisms that generate SVs, their heterogeneity across the human chromosomes as well as their variation between individuals, and developing rigorous statistical methodologies for identifying positive and negative selection on SVs in human somatic cells. Characterizing the landscape of somatic SVs is crucial for a more complete understanding of the genetic basis of carcinogenesis and of the variable cancer risk across tissues and individuals, and may also provide evidence for hypothesized roles of somatic genetic variation in aging-related pathologies more generally. Fields of science natural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepathologynatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesgeneticsgenomes Keywords structural variation indels mutational processes long-read genome sequencing genetic variant interpretation tumor evolution DNA replication and repair Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2022-COG - ERC CONSOLIDATOR GRANTS Call for proposal ERC-2022-COG See other projects for this call Funding Scheme HORIZON-ERC - HORIZON ERC Grants Host institution KOBENHAVNS UNIVERSITET Net EU contribution € 1 999 428,75 Address NORREGADE 10 1165 Kobenhavn Denmark See on map Region Danmark Hovedstaden Byen København Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 999 428,75 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all KOBENHAVNS UNIVERSITET Denmark Net EU contribution € 1 999 428,75 Address NORREGADE 10 1165 Kobenhavn See on map Region Danmark Hovedstaden Byen København Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 999 428,75 FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA) Participation ended Spain Net EU contribution € 0,00 Address CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA 08028 Barcelona See on map Region Este Cataluña Barcelona Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost No data
