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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
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
