Gaffney P M, Ortmann W A, Selby S A, Shark K B, Ockenden T C, Rohlf K E, Walgrave N L, Boyum W P, Malmgren M L, Miller M E, Kearns G M, Messner R P, King R A, Rich S S, Behrens T W
University of Minnesota Medical School, 312 Church Street, S.E., Minneapolis, MN 55455, USA.
Am J Hum Genet. 2000 Feb;66(2):547-56. doi: 10.1086/302767.
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 (Fcgamma) 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 >/=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.
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性。流行病学数据表明基因在狼疮病因中起重要作用，先前的基因研究已将HLA基因座、补体基因和低亲和力IgG（Fcγ）受体与SLE发病机制联系起来。为了确定SLE的新易感基因座，我们最近报告了在105个SLE同胞对家族中进行全基因组微卫星标记筛选的结果。通过使用非参数方法，在四个区间发现了连锁证据：6p11 - 21（靠近HLA）、16q13、14q21 - 23和20p12.3（LOD分数≥2.0），在另外九个区域发现了较弱的证据。我们现在报告在82个SLE同胞对家族的新队列中进行的第二次全基因组筛选结果。在队列2筛选中，四个最佳区间是7p22（LOD分数2.87）、7q21（LOD分数2.40）、10p13（LOD分数2.24）和7q36（LOD分数2.15）。另外八个区间的LOD分数在1.00 - 1.67范围内被确定。对队列1和队列2（187个同胞对家族）的联合分析表明，6p11 - p21（D6S426，LOD分数4.19）和16q13（D16S415，LOD分数3.85）中的标记符合显著连锁的标准。在联合样本中，三个区间（2p15、7q36和1q42）的LOD分数在1.92 - 2.06范围内，另外13个区间的LOD分数在1.00 - 1.78范围内。这些数据，连同SLE中其他可用的基因定位结果，开始允许对人类SLE基因发现工作的基因组区间进行优先级排序。
