Genome-wide screen for systemic lupus erythematosus susceptibility genes in multiplex families
Genome-wide screen for systemic lupus erythematosus susceptibility genes in multiplex families
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DOI：
10.1093/hmg/8.4.639
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发表时间：
1999-04-01
影响因子：
3.5
通讯作者：
Jacob, CO
中科院分区：
文献类型：
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作者：
Shai, R;Quismorio, FP;Jacob, CO
系统性红斑狼疮(SLE)是人类自身免疫性疾病的原型。其遗传成分已被家族聚集性(S=20)和双胞胎研究所证实。我们利用ABI Prism连锁图谱对人类基因组中可能包含狼疮易感基因的遗传区间进行了定位，该图谱包括：350个平均间距为12 cM的多态标记，非参数多点连锁分析提示在I号和18号染色体上存在易感基因座。然而，没有发现具有压倒性连锁证据的单个基因座，这表明在SLE家系中没有分离的主要易感基因，而且遗传病因更有可能是几个中等效应基因作用的结果。此外，在1q44区和1p36区对基因的支持明显只在患有SLE的墨西哥裔美国人家庭中发现，而在高加索人家庭中没有，这表明单独考虑每个种族是至关重要的。
Systemic lupus erythematosus (SLE) is the prototype of human autoimmune diseases. Its genetic component has been suggested by familial aggregation (lambda s=20) and twin studies. We have screened the human genome to localize genetic intervals that may contain lupus susceptibility loci in a sample of 188 lupus patients belonging to 80 lupus families with two or more affected relatives per family using the ABI Prism linkage mapping set which includes; 350 polymorphic markers with an average spacing of 12 cM, Non-parametric multipoint linkage analysis suggests evidence for predisposing loci on chromosomes I and 18. However, no single locus with overwhelming evidence for linkage was found, suggesting that there are no 'major' susceptibility genes segregating in families with SLE, and that the genetic etiology is more likely to result from the action of several genes of moderate effect. Furthermore, the support for a gene in the 1q44 region as well as in the 1p36 region is clearly found only in the Mexican American families with SLE but not in families of Caucasian ethnicity, suggesting that consideration of each ethnic group separately is crucial.