Evolutionary Selection and Constraint on Human Knee Chondrocyte Regulation Impacts Osteoarthritis Risk
Osteoarthritis has a considerable heritable component, with GWAS variants residing in non-coding sequences near chondrocyte genes; loci which likely became evolutionarily optimized during bipedal knee formation. To explore this relationship, we epigenetically profiled joint chondrocytes, revealing evidence of selection and constraint on human knee-specific regulatory elements. These elements also overlap osteoarthritis loci, with risk variants contributing to disease heritability by altering constrained sequences. Using these findings we then describe a causal enhancer variant present in half the world’s population, showing that it impacts mouse knee-shape and osteoarthritis. Overall, our methods link an evolutionarily novel aspect of anatomy to its pathogenesis.
Date: 2 September 2019, 12:00 (Monday, 19th week, Trinity 2019)
Venue: Kennedy Institute of Rheumatology, Headington OX3 7FY
Venue Details: Bernard Sunley Lecture Theatre
Speaker: Dr Terence Capellini (Richard B. Wolf Associate Professor of Human Evolutionary Biology at Harvard University)
Organising department: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS)
Organisers: Jennifer Pope (Kennedy Institute of Rheumatology), Jo Silva (NDORMS)
Organiser contact email address: jennifer.pope@kennedy.ox.ac.uk
Host: Professor Tonia Vincent (Kennedy Institute of Rheumatology)
Part of: Kennedy Institute Seminars
Booking required?: Not required
Audience: Public
Editor: Jennifer Pope