GENETIC ASSOCIATION WITH LUPUS IN AMERICAN BLACKS

我们发现系统性红斑狼疮与一种强有力的遗传联系 非裔美国人家庭的红斑。 我们目前的数据显示 比值比为9.0，卡方为9.55，p=0.002。 在相同基因座的 在美国白色家庭中， 多发性狼疮（比值比= 1.8，卡方= 0.04，p = 0.001）。 0.4）。 选择这些数据的遗传标记D1 S117是因为其接近 Fc γ受体IIIPMN基因，其产物是最 在正常人皮肤表面上有大量的免疫复合物受体， 中性粒细胞 该基因的罕见缺失已在两个 狼疮患者 初步的遗传模型显示，在2.17分， 纯合隐性效应的重组分数为零. D1 S117非裔美国人家庭在这个轨迹上有七个白色 在此模型下，任何家庭的lod得分均小于-2.0 复合频率低于0.07。 这项拟议的研究旨在评估这种遗传关联， 非裔美国家庭 我们计划收集更多的非洲人 多发性系统性红斑狼疮的美国家系。 然后，遗传模式的最佳模型将由下式确定： 应用最大似然分析算法。 通过评估 1号染色体上的其他多态位点，我们将定位连锁 interval. 来自受影响非洲人的Fc γ RIIIPMN基因的等位基因 狼疮患者将首先通过Southern印迹进行表征，然后通过 它们的单链构象多态性， 测序 如果与D1 S117连锁的基因是负责的，而不是Fc γ RIIIPMN本身，那么我们将应用选择克隆， 识别这个轨迹。 无论是否在Fc γ RIIIPMN，我们的目标是 这个项目是为了确定基因及其等位基因的差异， 在我们的研究中， 越来越多的非裔美国人的狼疮家系。

We have found a powerful genetic association with systemic lupus erythematosus in African American families. Our data to this point show an odds ration of 9.0, chi square of 9.55 and p=0.002. At the same locus there is no genetic association with lupus in American white families who are multiplex for lupus (odds ratio = 1.8, chi square = 0.04, and p = 0.4). The genetic marker for these data, D1S117, was chosen for its proximity to the Fcgamma receptor IIIPMN gene, the product of which is the most abundant receptor for immune complexes on the surface of normal neutrophils. Uncommon deletions in this gene have been identified in two lupus patients. Preliminary genetic modelling has revealed a lod score of 2.17 at a recombination fraction of zero for a homozygous recessive effect at D1S117 in African American families. At this locus in seven white families the lod score under this model is less than -2.0 for any recombination frequency lower than 0.07. The proposed study is designed to evaluate this genetic association in African Americans families. We plan to collect additional African American pedigrees who are multiplex for systemic lupus erythematosus. Then the optimal model for the mode of inheritance will be determined by applying the maximum likelihood algorithms of analysis. By evaluating the other polymorphic loci on chromosome 1 we will localize the linkage interval. Alleles of the Fcgamma RIIIPMN gene from affected African lupus patients will be characterized, first by Southern blot, then by their single stranded conformational polymorphisms and finally be sequencing. If a gene linked to D1S117 is responsible, but not Fcgamma RIIIPMN itself, then we will apply selection cloning in a quest to identify this locus. Whether at Fcgamma RIIIPMN or not, our goal during this project is to identify the gene and its allelic differences responsible for the observed genetic association with lupus in our growing collection of African American pedigrees multiplex for lupus.