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Regulatory constraint and selection during human knee evolution drive modern osteoarthritis risk

ABSTRACT: The evolution of human bipedalism exposed the knee to unique biomechanical challenges, requiring changes in knee anatomy giving rise to the modern-day configuration. In order to better understand the relationship between derived knee morphology and the genetic factors associated with osteoarthritis risk, we performed epigenetic profiling of murine forelimb/hindlimb growth plates to identify regulatory elements shaping formation of specific knee structures, identifying signals of ancient positive selection upon which more recent genetic drift overlaps risk-associated loci. Our functional analyses of an osteoarthritis-risk variant within a reproducibly-associated locus establishes a novel model for studying this degenerative disease.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE122877 | GEO | 2020/04/16

REPOSITORIES: GEO

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