Genevieve Housman1,2, Lorena M Havill3, Ellen E Quillen4, Anthony G Comuzzie4, Anne C Stone1,2. 1. 1 School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, USA. 2. 2 Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA. 3. 3 Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA. 4. 4 Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
Abstract
OBJECTIVE: Osteoarthritis (OA) affects humans and several other animals. Thus, the mechanisms underlying this disorder, such as specific skeletal tissue DNA methylation patterns, may be evolutionary conserved. However, associations between methylation and OA have not been readily studied in nonhuman animals. Baboons serve as important models of disease and develop OA at rates similar to those in humans. Therefore, this study investigated the associations between methylation and OA in baboons to advance the evolutionary understanding of OA. DESIGN: Trabecular bone and cartilage was collected from the medial condyles of adult female baboon femora, 5 with and 5 without knee OA. The Infinium HumanMethylation450 BeadChip (450K array) was used to identify DNA methylation patterns in these tissues. RESULTS: Approximately 44% of the 450K array probes reliably align to the baboon genome, contain a CpG site of interest, and maintain a wide distribution throughout the genome. Of the 2 filtering methods tested, both identified significantly differentially methylated positions (DMPs) between healthy and OA individuals in cartilage tissues, and some of these patterns overlap with those previously identified in humans. Conversely, no DMPs were found between tissue types or between disease states in bone tissues. CONCLUSIONS: Overall, the 450K array can be used to measure genome-wide DNA methylation in baboon tissues and identify significant associations with complex traits. The results of this study indicate that some DNA methylation patterns associated with OA are evolutionarily conserved, while others are not. This warrants further investigation in a larger and more phylogenetically diverse sample set.
OBJECTIVE:Osteoarthritis (OA) affects humans and several other animals. Thus, the mechanisms underlying this disorder, such as specific skeletal tissue DNA methylation patterns, may be evolutionary conserved. However, associations between methylation and OA have not been readily studied in nonhuman animals. Baboons serve as important models of disease and develop OA at rates similar to those in humans. Therefore, this study investigated the associations between methylation and OA in baboons to advance the evolutionary understanding of OA. DESIGN: Trabecular bone and cartilage was collected from the medial condyles of adult female baboon femora, 5 with and 5 without knee OA. The Infinium HumanMethylation450 BeadChip (450K array) was used to identify DNA methylation patterns in these tissues. RESULTS: Approximately 44% of the 450K array probes reliably align to the baboon genome, contain a CpG site of interest, and maintain a wide distribution throughout the genome. Of the 2 filtering methods tested, both identified significantly differentially methylated positions (DMPs) between healthy and OA individuals in cartilage tissues, and some of these patterns overlap with those previously identified in humans. Conversely, no DMPs were found between tissue types or between disease states in bone tissues. CONCLUSIONS: Overall, the 450K array can be used to measure genome-wide DNA methylation in baboon tissues and identify significant associations with complex traits. The results of this study indicate that some DNA methylation patterns associated with OA are evolutionarily conserved, while others are not. This warrants further investigation in a larger and more phylogenetically diverse sample set.
Entities:
Keywords:
DNA methylation; animal model; articular cartilage; bone; osteoarthritis
Authors: Andy T Kwok; Joseph E Moore; Samuel Rosas; Bethany A Kerr; Rachel N Andrews; Callistus M Nguyen; Jingyun Lee; Cristina M Furdui; Boyce E Collins; Michael T Munley; Jeffrey S Willey Journal: Radiat Res Date: 2019-03-29 Impact factor: 2.841
Authors: Wanding Zhou; Toshinori Hinoue; Bret Barnes; Owen Mitchell; Waleed Iqbal; Sol Moe Lee; Kelly K Foy; Kwang-Ho Lee; Ethan J Moyer; Alexandra VanderArk; Julie M Koeman; Wubin Ding; Manpreet Kalkat; Nathan J Spix; Bryn Eagleson; John Andrew Pospisilik; Piroska E Szabó; Marisa S Bartolomei; Nicole A Vander Schaaf; Liang Kang; Ashley K Wiseman; Peter A Jones; Connie M Krawczyk; Marie Adams; Rishi Porecha; Brian H Chen; Hui Shen; Peter W Laird Journal: Cell Genom Date: 2022-07-13