Rheumatoid arthritis: identifying and characterising polymorphisms using rat models
Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this dis...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2016-10-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/9/10/1111 |
| _version_ | 1828473615000010752 |
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| author | Anthony C. Y. Yau Rikard Holmdahl |
| author_facet | Anthony C. Y. Yau Rikard Holmdahl |
| author_sort | Anthony C. Y. Yau |
| collection | DOAJ |
| description | Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. |
| first_indexed | 2024-12-11T05:47:05Z |
| format | Article |
| id | doaj.art-b240e55feeff46dca73156cc121bc275 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-11T05:47:05Z |
| publishDate | 2016-10-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-b240e55feeff46dca73156cc121bc2752022-12-22T01:18:56ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112016-10-019101111112310.1242/dmm.026435026435Rheumatoid arthritis: identifying and characterising polymorphisms using rat modelsAnthony C. Y. Yau0Rikard Holmdahl1 Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans.http://dmm.biologists.org/content/9/10/1111Rat modelsRheumatoid arthritisGeneticsSusceptibility genesChronic inflammationCongenic mapping |
| spellingShingle | Anthony C. Y. Yau Rikard Holmdahl Rheumatoid arthritis: identifying and characterising polymorphisms using rat models Disease Models & Mechanisms Rat models Rheumatoid arthritis Genetics Susceptibility genes Chronic inflammation Congenic mapping |
| title | Rheumatoid arthritis: identifying and characterising polymorphisms using rat models |
| title_full | Rheumatoid arthritis: identifying and characterising polymorphisms using rat models |
| title_fullStr | Rheumatoid arthritis: identifying and characterising polymorphisms using rat models |
| title_full_unstemmed | Rheumatoid arthritis: identifying and characterising polymorphisms using rat models |
| title_short | Rheumatoid arthritis: identifying and characterising polymorphisms using rat models |
| title_sort | rheumatoid arthritis identifying and characterising polymorphisms using rat models |
| topic | Rat models Rheumatoid arthritis Genetics Susceptibility genes Chronic inflammation Congenic mapping |
| url | http://dmm.biologists.org/content/9/10/1111 |
| work_keys_str_mv | AT anthonycyyau rheumatoidarthritisidentifyingandcharacterisingpolymorphismsusingratmodels AT rikardholmdahl rheumatoidarthritisidentifyingandcharacterisingpolymorphismsusingratmodels |