Genome screening in human systemic lupus erythematosus: Results from a second Minnesota cohort and combined analyses of 187 sib-pair families
Genome screening in human systemic lupus erythematosus: Results from a second Minnesota cohort and combined analyses of 187 sib-pair families
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DOI：
10.1086/302767
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发表时间：
2000-02-01
影响因子：
9.8
通讯作者：
Behrens, TW
中科院分区：
文献类型：
--
作者：
Gaffney, PM;Ortmann, WA;Behrens, TW
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征是对多种自身抗原失去免疫耐受。流行病学数据表明基因在狼疮病因中发挥着重要作用，之前的遗传学研究表明 HLA 基因座、补体基因和低亲和力 IgG (Fc gamma) 受体与 SLE 发病机制有关。为了确定 SLE 新的易感位点，我们最近报告了 105 个 SLE 同胞对家族的全基因组微卫星标记筛选结果。通过使用非参数方法，在四个区间中发现了连锁证据：6p11-21（靠近 HLA）、16q13、14q21-23 和 20p12.3（LOD 分数大于或等于 2.0），而在另外 9 个区域中则发现了较弱的证据。我们现在报告对 82 个 SLE 同胞对家族进行第二次完整基因组筛查的结果。在队列 2 筛选中，四个最佳间隔为 7p22（LOD 得分 2.87）、7q21（LOD 得分 2.40）、10p13（LOD 得分 2.24）和 7q36（LOD 得分 2.15）。确定了另外八个区间，其 LOD 分数在 1.00-1.67 范围内。对 MN 队列 1 和 2（187 个同胞对家庭）的联合分析显示，6p11-p21（D6S426，LOD 评分 4.19）和 16q13（D16S415，LOD 评分 3.85）中的标记符合显着连锁的标准。在组合样本中，三个间隔（2p15、7q36 和 1q42）的 LOD 分数在 1.92-2.06 范围内，另外 13 个间隔的 LOD 分数在 1.00-1.78 范围内。这些数据与 SLE 中其他可用的基因图谱结果一起，开始允许对人类 SLE 基因发现工作的基因组区间进行优先排序。
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a loss of immunologic tolerance to a multitude of self-antigens. Epidemiological data suggest an important role for genes in the etiology of lupus, and previous genetic studies have implicated the HLA locus, complement genes, and low-affinity IgG (Fc gamma) receptors in SLE pathogenesis. In an effort to identify new susceptibility loci for SLE, we recently reported the results of a genomewide microsatellite marker screen in 105 SLE sib-pair families. By using nonparametric methods, evidence for linkage was found in four intervals: 6p11-21 (near the HLA), 16q13, 14q21-23, and 20p12.3 (LOD scores greater than or equal to 2.0), and weaker evidence in another nine regions. We now report the results of a second complete genome screen in a new cohort of 82 SLE sib-pair families. In the cohort 2 screen, the four best intervals were 7p22 (LOD score 2.87), 7q21 (LOD score 2.40), 10p13 (LOD score 2.24), and 7q36 (LOD score 2.15). Eight additional intervals were identified with LOD scores in the range 1.00-1.67. A combined analysis of MN cohorts 1 and 2 (187 sib-pair families) showed that markers in 6p11-p21 (D6S426, LOD score 4.19) and 16q13 (D16S415, LOD score 3.85) met the criteria for significant linkage. Three intervals (2p15, 7q36, and 1q42) had LOD scores in the range 1.92-2.06, and another 13 intervals had LOD scores in the range of 1.00-1.78 in the combined sample. These data, together with other available gene mapping results in SLE, are beginning to allow a prioritization of genomic intervals for gene discovery efforts in human SLE.