近期发表在《Annals of the Rheumatic Diseases》上的一篇实验文章指出，关节炎敏感系DA大鼠与抵抗系 PVG.1AV1 的高代互交系(advanced intercross line,AIL)大鼠具有某些危险基因，与关节炎有相关性。
研究人员进行了一项实验研究，旨在分析与人关节炎基因区域对应的大鼠关节炎基因区域，他们给关节炎敏感系DA大鼠与抵抗系 PVG.1AV1 的高代互交系(advanced intercross line,AIL)大鼠注射不同的致关节炎油，分析基因型与表型的关系。结果显示注射降植烷(pristane)关节炎的发生率高（57%），降植烷诱导的关节炎与关节炎基因决定域 Ncf1 和 APLEC 中小于 130kb 的基因片断有最大相关性；5个新的数量性状基因座(Quantitative trait loci, QTL) 定位于与大鼠染色体4号和10号，可信区间很窄，部分表现出慢性关节炎和性别差异。人类相似的基因区域含有转座子，如编码蛋白激酶α和白介素IL-17α。因此，他们得出结论 AIL 系种群具有某些危险基因，与关节炎有相关性。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
