
Development and validation of animal variant classification guidelines to objectively evaluate genetic variant pathogenicity in domestic animals
- Author
- Fréderique Boeykens (UGent) , Marie Abitbol, Heidi Anderson, Iris Casselman (UGent) , Caroline Dufaure de Citres, Jessica J. Hayward, Jens Häggström, Mark D. Kittleson, Elvio Lepri, Ingrid Ljungvall, Maria Longeri, Leslie A. Lyons, Åsa Ohlsson, Luc Peelman (UGent) , Pascale Smets (UGent) , Tommaso Vezzosi, Frank G. van Steenbeek and Bart Broeckx (UGent)
- Organization
- Project
- Abstract
- Assessing the pathogenicity of a disease-associated genetic variant in animals accurately is vital, both on a population and individual scale. At the population level, breeding decisions based on invalid DNA tests can lead to the incorrect inclusion or exclusion of animals and compromise the long-term health of a population, and at the level of the individual animal, lead to incorrect treatment and even life-ending decisions. Criteria to determine pathogenicity are not standardized, i.e., no guidelines for animal variants are available. Here, we aimed to develop and validate guidelines to be used by the community for Mendelian disorders in domestic animals to classify variants in categories based on standardized criteria. These so-called animal variant classification guidelines (AVCG) were based on those developed for humans by The American College of Medical Genetics and Genomics (ACMG). In a direct comparison, 83% of the pathogenic variants were correctly classified with ACMG, while this increased to 92% with AVCG. We described methods to develop datasets for benchmarking the criteria and identified the most optimal in silico variant effect predictor tools. As the reproducibility was high, we classified 72 known disease-associated variants in cats and 40 other disease-associated variants in eight additional species.
- Keywords
- (clinical) genetic testing, genetic variant datasets, interpretation, reproducibility, <italic>in silico</italic> variant effect predictor tools, across-species classification, pathogenic, neutral, POLYCYSTIC KIDNEY-DISEASE, POPULATION-STRUCTURE, MISSENSE MUTATIONS, DOG BREEDS, DIVERSITY, IMPACT, RECOMMENDATIONS, ASSOCIATION, CLINGEN, CATS
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JGYHKAV1V2AXMQDNN683N5XR
- MLA
- Boeykens, Fréderique, et al. “Development and Validation of Animal Variant Classification Guidelines to Objectively Evaluate Genetic Variant Pathogenicity in Domestic Animals.” FRONTIERS IN VETERINARY SCIENCE, edited by Claire Rebecca Sharp, vol. 11, 2024, doi:10.3389/fvets.2024.1497817.
- APA
- Boeykens, F., Abitbol, M., Anderson, H., Casselman, I., de Citres, C. D., Hayward, J. J., … Broeckx, B. (2024). Development and validation of animal variant classification guidelines to objectively evaluate genetic variant pathogenicity in domestic animals. FRONTIERS IN VETERINARY SCIENCE, 11. https://doi.org/10.3389/fvets.2024.1497817
- Chicago author-date
- Boeykens, Fréderique, Marie Abitbol, Heidi Anderson, Iris Casselman, Caroline Dufaure de Citres, Jessica J. Hayward, Jens Häggström, et al. 2024. “Development and Validation of Animal Variant Classification Guidelines to Objectively Evaluate Genetic Variant Pathogenicity in Domestic Animals.” Edited by Claire Rebecca Sharp. FRONTIERS IN VETERINARY SCIENCE 11. https://doi.org/10.3389/fvets.2024.1497817.
- Chicago author-date (all authors)
- Boeykens, Fréderique, Marie Abitbol, Heidi Anderson, Iris Casselman, Caroline Dufaure de Citres, Jessica J. Hayward, Jens Häggström, Mark D. Kittleson, Elvio Lepri, Ingrid Ljungvall, Maria Longeri, Leslie A. Lyons, Åsa Ohlsson, Luc Peelman, Pascale Smets, Tommaso Vezzosi, Frank G. van Steenbeek, and Bart Broeckx. 2024. “Development and Validation of Animal Variant Classification Guidelines to Objectively Evaluate Genetic Variant Pathogenicity in Domestic Animals.” Ed by. Claire Rebecca Sharp. FRONTIERS IN VETERINARY SCIENCE 11. doi:10.3389/fvets.2024.1497817.
- Vancouver
- 1.Boeykens F, Abitbol M, Anderson H, Casselman I, de Citres CD, Hayward JJ, et al. Development and validation of animal variant classification guidelines to objectively evaluate genetic variant pathogenicity in domestic animals. Sharp CR, editor. FRONTIERS IN VETERINARY SCIENCE. 2024;11.
- IEEE
- [1]F. Boeykens et al., “Development and validation of animal variant classification guidelines to objectively evaluate genetic variant pathogenicity in domestic animals,” FRONTIERS IN VETERINARY SCIENCE, vol. 11, 2024.
@article{01JGYHKAV1V2AXMQDNN683N5XR, abstract = {{Assessing the pathogenicity of a disease-associated genetic variant in animals accurately is vital, both on a population and individual scale. At the population level, breeding decisions based on invalid DNA tests can lead to the incorrect inclusion or exclusion of animals and compromise the long-term health of a population, and at the level of the individual animal, lead to incorrect treatment and even life-ending decisions. Criteria to determine pathogenicity are not standardized, i.e., no guidelines for animal variants are available. Here, we aimed to develop and validate guidelines to be used by the community for Mendelian disorders in domestic animals to classify variants in categories based on standardized criteria. These so-called animal variant classification guidelines (AVCG) were based on those developed for humans by The American College of Medical Genetics and Genomics (ACMG). In a direct comparison, 83% of the pathogenic variants were correctly classified with ACMG, while this increased to 92% with AVCG. We described methods to develop datasets for benchmarking the criteria and identified the most optimal in silico variant effect predictor tools. As the reproducibility was high, we classified 72 known disease-associated variants in cats and 40 other disease-associated variants in eight additional species.}}, articleno = {{1497817}}, author = {{Boeykens, Fréderique and Abitbol, Marie and Anderson, Heidi and Casselman, Iris and de Citres, Caroline Dufaure and Hayward, Jessica J. and Häggström, Jens and Kittleson, Mark D. and Lepri, Elvio and Ljungvall, Ingrid and Longeri, Maria and Lyons, Leslie A. and Ohlsson, Åsa and Peelman, Luc and Smets, Pascale and Vezzosi, Tommaso and van Steenbeek, Frank G. and Broeckx, Bart}}, editor = {{Sharp, Claire Rebecca}}, issn = {{2297-1769}}, journal = {{FRONTIERS IN VETERINARY SCIENCE}}, keywords = {{(clinical) genetic testing,genetic variant datasets,interpretation,reproducibility,<italic>in silico</italic> variant effect predictor tools,across-species classification,pathogenic,neutral,POLYCYSTIC KIDNEY-DISEASE,POPULATION-STRUCTURE,MISSENSE MUTATIONS,DOG BREEDS,DIVERSITY,IMPACT,RECOMMENDATIONS,ASSOCIATION,CLINGEN,CATS}}, language = {{eng}}, pages = {{17}}, title = {{Development and validation of animal variant classification guidelines to objectively evaluate genetic variant pathogenicity in domestic animals}}, url = {{http://doi.org/10.3389/fvets.2024.1497817}}, volume = {{11}}, year = {{2024}}, }
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