GENETIC ASSOCIATION WITH LUPUS IN AMERICAN BLACKS

我们发现系统性红斑狼疮与基因有很强的关联 非洲裔美国人家庭中的红斑狼疮。我们到目前为止的数据显示 优势比为9.0，卡方检验为9.55，P=0.002。在相同的轨迹上 在那些患有狼疮的美国白人家庭中，没有遗传因素与狼疮有关 对于狼疮(优势比=1.8，卡方=0.04，p= 0.4)。 这些数据的遗传标记D1S117是因为它的近似性而被选择的 对FcGamma受体IIIPMN基因，其产物是 正常人表面丰富的免疫复合体受体 中性粒细胞。在两个基因中发现了这种基因罕见的缺失 狼疮患者。 初步的遗传模型显示，在一年中，Lod得分为2.17 纯合子隐性效应的重组分数为零 D1S117在非裔美国人家庭中的分布。在这条七白的轨迹上 在此模型下，家庭成员的Lod得分小于-2.0 重组频率低于0.07。 这项拟议的研究旨在评估这种遗传联系在 非裔美国人家庭。我们计划收集更多的非洲人 系统性红斑狼疮的多发性美国家系。 那么遗传模式的最优模型将由以下公式确定 应用最大似然算法进行分析。通过评估 我们将对1号染色体上的其他多态基因座进行定位 时间间隔。非洲患者FcGamma RIIIPMN基因的等位基因研究 狼疮患者的特征是，首先是Southern印迹，然后是 它们的单链构象多态最终是 测序。如果与D1S117相关的基因负责，而不是FcGamma RIIIPMN本身，然后我们将应用选择克隆来探索 确定这个基因的位置。无论是否在FcGamma RIIIPMN，我们的目标是在 本项目旨在鉴定该基因及其等位基因的差异。 对观察到的与狼疮的遗传关联负责 越来越多的非裔美国人狼疮家系的收集。

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.