The core expertise of the Medical Genomics Thematic Unit (GTU) is the forward and reverse genetic dissection of complex inherited traits in mammals. Research activities of the thematic unit can be grouped in four main topics:
1. Medical genomics - genetic dissection of inherited predisposition to inflammatory bowel disease (IBD) and cancer
The GTU is an active member of the Belgian and International IBD Genetics Consortia. We are using state-of-the-art genomic methodologies to map risk loci for IBD, to identify causative genes and variants within these loci, and to study the role of the intestinal microbiota in the pathogenesis of IBD. We study the utility of quasi-infinitesimal models for IBD diagnosis and progression. We are searching for germline and somatic variants associated with cancers including familial isolated pituitary adenomas, breast cancer and glyoblastoma. The GTU coordinates the Belgian Medical Genomics Initiative (BeMGI) and wants in that capacity to play a catalyzing role in the adoption of genomic information in the clinic.
2. Animal genomics phenotype and genotype-driven screens for agronomically important genes and variants & genomic selection
we are using the same state-of-the-art genomics tool box to identify genes and variants underlying inherited defects, embryonic lethals and breeding values for economically important traits, including disease resistance. We are developing methods that exploit genomic information, including sequence data, for selection, i.e. «genomic selection». We work mainly in cattle and pigs, and collaborate closely with breeding organizations in Belgium, the Netherlands and New Zealand.
3. Fundamental genomics polar overdominance, mutation and recombination in the germline, and transgenerational genetic effects
we work on the genetic dissection of polar overdominance in callipyge sheep: an unsual inheritance pattern that involves miRNA-mediated cross-talk between the paternal and maternal homologues at the CLPG locus. We are taking advantage of the unique pedigree structure of cow populations to quantify and genetically dissect inter-individual variation in de novo mutation, gene conversion and recombination rates in the bovine germline. We use a mouse model based on chromosome substitution strains to study the importance and mechanisms underlying transgenerational genetic effects.
4. BLV genomics - role and modus operandi of BLV-encoded miRNAs
the team of Anne Van den Broeke continues to study the role of the cluster of miRNAs that they discovered in the retroviral BLV genome. Genomic approaches are being applied to gain new understandings in BLV- and HTLV-dependent leukemogenesis.
L’identification des gènes responsables de la prédisposition à la maladie de Crohn et la colite ulcéro-hémorragique parmi environ 600 candidats positionnels se resserre. Des équipes de l'Institut Sanger du Wellcome Trust Sanger, du Broad Institute de MIT et Harvard, et de l’Institut GIGA de l'Université de Liège s’attellent à la production d’une carte à très haute définition des variants génétiques prédisposant à ces maladies.