【摘要】 为了寻找中国人群强直性脊柱炎 (ankylosingspondylitis ,AS)的易感基因位点 ,采用全基因组扫描法对 9个强直性脊柱炎家系进行基因分型、参数连锁分析和非参数连锁分析。在参数连锁分析中 ,D6S2 76位点的最大LOD值为 3 882 1(θ =0 0 ) ,精细分析显示距D6S2 76位点附近的D6S1691和D6S1618的LOD值分别为 1 5717(θ =0 1)及2 0 0 56(θ =0 1)。在非参数连锁分析中 ,位于D6S2 76附近的LOD值高达 5 0 62 3 ,非参数连锁分析的NPL值为3 7561,最小P值为 0 0 0 0 2 3 3。上述结果提示 ,D6S2 76与强直性脊柱炎之间存在较强的连锁关系 ,D6S1691 D6S2 76 D6S1618区域可能存在强直性脊柱炎的易感基因位点。此外 ,D3S12 92、D4S153 5和D18S64的最大LOD值分别为1 2 768(θ =0 2 )、1 12 46(θ =0 2 )和 1 1851(θ =0 1) ,提示这些标记与AS之间存在一定的连锁关系更多还原

【Abstract】 Ankylosing spondylitis (AS) is a common inflammatory arthritis,with a prevalence of 1‰～3‰ in Caucasian and 2‰ in Chinese population.The recognition of the association of HLA-B27 with AS confirmed the importance of heritable factors in the disease.Whole-genome scans showed that some affected-sibling-pair families with AS not only demonstrated strong linkage to the MHC locus,but also identified other regions with suggestive or stronger linkage on chromosomes 1p,2q,9q,10q,16q and 19q.In order to localize the regions containing genes that determine susceptibility to AS in Chinese Han population,a genomewide screen was performed in nine Chinese families with AS,including 29 affected individuals.LINKAGE and GENEHUNTER packages were used for parametric (LOD) and non-parametric (NPL) analysis.The significant two-point LOD score value with D6S276 (at 44.9 cM from the 6p terminal) was 3.8821 in parametric analysis.Fine mapping showed LOD scores of D6S1691(at 42.7 cM) and D6S1618 (at 47.6 cM) around D6S276 were 1.5717 and 2.0056,respectively.Single point NPL score of D6S276,D6S1691 and D6S1618 were 2.6053,2.7490,2.0202,respectively,and minimum P value were 0.0072,0.0047,and 0.0265,respectively.Using multipoint NPL,the maximum LOD score values,NPL score and minimum P value obtained near D6S276 were 5.0623,3.7561,and 0.000233,respectively.As a result,the strong linkage of the D6S276 with AS was found,the region of D6S1691-D6S276-D6S1618 existed a susceptibility gene of AS.In addition,the LOD scores of D3S1292,D4S1535 and D18S64 were larger than 1.0,so they might be some suggestive linkage markers with AS.更多还原