近期發(fā)表在《Annals of the Rheumatic Diseases》上的一篇實驗文章指出,，關節(jié)炎敏感系DA大鼠與抵抗系 PVG.1AV1 的高代互交系(advanced intercross line,AIL)大鼠具有某些危險基因,，與關節(jié)炎有相關性,。
研究人員進行了一項實驗研究,，旨在分析與人關節(jié)炎基因區(qū)域對應的大鼠關節(jié)炎基因區(qū)域,，他們給關節(jié)炎敏感系DA大鼠與抵抗系 PVG.1AV1 的高代互交系(advanced intercross line,AIL)大鼠注射不同的致關節(jié)炎油,，分析基因型與表型的關系,。結果顯示注射降植烷(pristane)關節(jié)炎的發(fā)生率高（57%）,，降植烷誘導的關節(jié)炎與關節(jié)炎基因決定域 Ncf1 和 APLEC 中小于 130kb 的基因片斷有最大相關性；5個新的數(shù)量性狀基因座(Quantitative trait loci, QTL) 定位于與大鼠染色體4號和10號,，可信區(qū)間很窄,，部分表現(xiàn)出慢性關節(jié)炎和性別差異。人類相似的基因區(qū)域含有轉座子,，如編碼蛋白激酶α和白介素IL-17α,。因此，他們得出結論 AIL 系種群具有某些危險基因,，與關節(jié)炎有相關性,。（生物谷Bioon.com）
生物谷推薦原始出處：
Ann Rheum Dis.9 December 2008. doi:10.1136/ard.2008.090803
Definition of arthritis candidate risk genes by combining rat linkage-mapping results with human case control association data
Liselotte B?ckdahl 1, Jian Ping Guo 1, Maja Jagodic 1, Kristina Becanovic 1, Bo Ding 1, Tomas Olsson 1 and Johnny C. Lorentzen 1*
1 Karolinska Institutet, Sweden
Objective: To define genomic regions that link to rat arthritis, and to determine the potential association with rheumatoid arthritis (RA) of the corresponding human genomic regions.
Methods: Advanced intercross lines (AIL) between arthritis susceptible DA rats and arthritis resistant PVG.1AV1 rats were injected with differently arthritogenic oils to achieve an experimental situation with substantial phenotypic variation in the rat study population. Genotyping of microsatellite markers was performed over genomic regions with documented impact on arthritis, located on rat chromosomes 4, 10, and 12. Linkage between genotypes and phenotypes were determined by R/QTL. Potential association with RA of single nucleotide polymorphisms (SNPs) in homologous human chromosome regions was evaluated from public WTCCC data derived from 2000 cases and 3000 controls.
Results: High frequency of arthritis (57 %) was recorded in 422 rats injected with pristane. Maximum linkage to pristane-induced arthritis occurred less than 130 kb from the known genetic arthritis determinants Ncf1 and APLEC, demonstrating remarkable mapping precision. Five novel quantitative trait loci were mapped on rat chromosomes 4 and 10, with narrow confidence intervals. Some exerted sex-biased effects and some were linked to chronic arthritis. Human homologous genomic regions contain loci where multiple nearby SNPs associate nominally with RA, e.g. at the genes encoding protein kinase C alpha and interleukin-17 receptor alpha.
Conclusions: High-resolution mapping in AIL populations defines limited sets of candidate risk genes, some of which appear also to associate with RA and thus may give clues to evolutionarily conserved pathways that lead to arthritis.
