Research concerning the genes responsible for osteoarthritis by association study and sib-pair linkage analysis

为了寻找骨关节炎（OA）的致病基因，本研究对模型小鼠OA致病基因进行关联分析，并进行同胞对连锁分析。骨关节炎患者基因组DNA的采集收集了173例散发性骨关节炎患者和29例家族性骨关节炎患者（38对同胞）的基因组DNA。骨关节炎模型小鼠致病基因的分析本研究对骨关节炎模型小鼠致病基因进行了相关性研究，克隆了一个与骨关节炎模型小鼠致病基因相似的人类同源基因。测定了ANKH基因全长cDNA和启动子区的核苷酸序列。采用PCR-SSCP和直接测序法对40份基因组DNA进行ANKH基因序列变异的研究。结果发现5个多态性位点，分别为编码区A1303 G、31非翻译区G1831 A、5'非翻译区8个碱基对缺失、启动子区-785A/G和-639delC。对202例OA患者和103例非OA对照者的基因多态性与OA的相关性进行qui-square检验。结果表明，ANKH基因51位非翻译区8个碱基对缺失与骨关节炎的发生有关，提示ANKH基因在骨关节炎的发病中有一定的作用。发现。同胞对连锁分析收集的家系样本不足以进行同胞对连锁分析。需要进一步收集。

In order to search die genes responsible for osteoarthritis (OA), association study between the gene responsible for the model mouse and osteoarthritis were performed and sib-pair linkage analysis were projected,1. Collecting genomic DNA of osteoarthritis patientsGenomic DNAs of 173 sporadic cases and 29 family cases (38 sibpairs), who have osteoarthritis without influence of injury, were collected,2. Analysis of the gene responsible for the osteoarthritis model mouseAssociation, study between the gene responsible for the model mouse and osteoarthritis was performed, A human homologue of mouse ank, which is responsible, for the OA model mouse, was cloned. The nucleotide sequence of full-length cDNA and promoter region of the ANKH gene was elucidated. Using 40 samples of genomic DNA, sequence variances in the ANKH gene were searched by PCR-SSCP and direct sequencing method. Five polymorphisms were found, A1303G in coding region, G1831A in 31untranslated region, eight-base-pairs deletionin 5' untranslated region, -785A/G and -639 delC in the promoter region. Using 202 samples of 0 A patients and 103 samples of non-OA controls, association between these polymorphisms and OA were analyzed by qui-square test. An association between eight-base-pairs deletion in 51untranslated region and OA was So it found. So it was found. Suggested that the ANKH gene has influence in the etiology of osteoarthritis. Found.3. Sib-pair linkage analysisCollected samples of family cases are not enough to perform the sib -pair linkage analysis. Further collection is necessary.