Gene Mapping in Women with Systemic Lupus Erythematosus

描述（由申请人提供）：此竞争性续期申请 概述了我们绘制并最终确定易感基因的计划， 人类系统性红斑狼疮在第一次融资期间，我们 已成功招募了超过250个SLE同胞对和多重家族， 以及130个三人（双亲均患病的SLE患者）家庭。全基因 在这些明尼苏达州的家系中进行了标记筛选， 染色体区域似乎可能含有SLE易感基因， 被识别。密集微卫星标记绘图已于2004年启动。 几个染色体区域显示出最令人信服的证据， 在我们的家族收集（1 q41，6p 21（HLA），16 q21，20 q和20 p）中。更 最近，我们已经开始分析这些区域中的几个候选基因。 我们的SLE家族是世界上最大的家族之一， 在下一个资助期内将该项目向前推进。在 在接下来的五年里，我们建议继续收集更多的SLE同胞对， 三人组家庭，目标是招募125个同胞对家庭和300个三人组。 此外，我们将收集一组200名年龄，性别和种族匹配的 用于病例/对照关联研究的对照个体， 标记数据。我们将进一步细化易感基因座的位置 在HLA区域内使用重组祖先单倍型方法，和 然后尝试识别HLA内的序列变异， SLE的风险最后，我们将继续在非HLA染色体上进行精细定位， 与狼疮表型相关的区域。在2010年的时间框架内， 未来五年，我们希望开始确定疾病相关序列 基因多态性赋予人类SLE的风险。狼疮的鉴别 基因对于我们进一步理解这一点至关重要 疾病，并合理地针对新的疗法。

DESCRIPTION (provided by applicant): This competitive renewal application outlines our plans to to map and eventually identify the susceptibility genes for human systemic lupus erythematosus. During the first funding period, we have successfully recruited over 250 SLE sib-pair and multiplex families, as well as 130 trio (affected SLE patient with both parents) families. Genome-wide marker screens have been performed in these Minnesota pedigrees, and several chromosomal regions that appear likely to harbor SLE susceptibility genes have been identified. Dense microsatellite marker mapping has been initiated in several chromosomal regions that show the most convincing evidence for linkage in our family collection (1q41, 6p21 (HLA), 16q21, 20q, and 20p). More recently, we have begun to analyze several candidate genes in these regions. Our collection of SLE families is one of the largest in the world, and we are well poised to move this project forward in the next funding period. In the next five years we propose to continue collection additional SLE sib-pair and trio families, with a goal of recruiting 125 sib-pair families and 300 trios. In addition we will collect a group of 200 age-, sex- and ethnicity-matched control individuals for case/control association studies with the accumulated marker data. We will further refine the location of the susceptibility loci within the HLA region using the recombinant ancestral haplotype approach, and then attempt to identify the sequence variations within the HLA that confer risk for SLE. Finally, we will continue fine mapping in the non-HLA chromosomal regions that show linkage to the lupus phenotype. Within the time frame of the next five years we hope to begin identifying the disease-associated sequence polymorphisms that confer risk for human SLE. The identification of the lupus genes will be critically important for furthering our understanding of this disease, and for rationally targeting new therapies.