GENETIC FINE MAPPING IN SLE PAIR FAMILIES

系统性红斑狼疮和高血压病患者的家族聚集性 同卵双胞胎的符合率表明有很强的遗传 系统性红斑狼疮易感性成分。作为一种识别身份的方法 对于狼疮基因，我们的实验室目前正在进行全基因组 标记筛选，努力定位染色体区域 港湾狼疮基因。至少有两个SLE患者的180多个家庭 亲属(主要是兄弟姐妹家庭)参加了这项研究。在……里面 初步研究表明，人类1号染色体的三个不同区域 105对系统性红斑狼疮同胞中可能存在连锁的证据 家人。随着基因组筛查的进行，很可能另一个候选者 间隔期将出现在其他染色体上。 SCOR项目的主要目标是加速基因搜索 MN SLE系列收藏。这将通过共享正在进行的 与OMRF(项目2)的同事进行基因分型数据比较 结果生成了两个SLE家族集合。初步测绘结果位于 MN还将与我们在UAB(项目3)的同事共享，以提供帮助 在他们筛选1Q染色体候选基因时。MN家族 然后将使用OMRF研究的标记对收集的样品进行基因分型，因此 这种连锁结果可以直接进行比较。有趣的染色体 然后，将优先考虑高密度标记屏幕和精细的区域 映射。三个家庭(一名双亲都患有SLE的患者) 此SCOR应用程序的组件将用于不平衡映射 在目标区域。然后将采用各种策略来 鉴定这些区域的系统性红斑狼疮基因(S)。 SLE基因的最终分离和克隆将提供第一个 有机会在基因水平上了解导致 狼疮患者的临床免疫紊乱特点。 这些见解应该会为这种患者提供新的治疗途径， 包括体细胞基因治疗的可能性。有趣的是，狼疮- 易患自身免疫病的家庭其他自身免疫性疾病的发病率也有所增加。 包括类风湿性关节炎、甲状腺疾病和糖尿病在内的疾病。 因此，识别导致人类系统性红斑狼疮的基因可能会 提高我们对器官的遗传学和病理生理学的理解- 特定的自身免疫力。

The familial clustering of systemic lupus erythematosus (SLE) and the high rate of concordance in monozygotic twins suggests a strong genetic component for susceptibility to SLE. As one approach to the identification of lupus genes, our laboratory is currently performing a genome-wide marker screen in an effort to localized the chromosomal regions that harbor lupus genes. Over 180 families with at least two affected SLE relatives (mostly sib pair families) are enrolled in this study. In preliminary studies, three distinct regions of human Chromosome 1 show evidence of possible linkage in an initial cohort of 105 SLE sib pair families. As the genome screen proceeds it is likely that other candidate intervals will emerge on other chromosomes. The primary goal of the SCOR project is to accelerate the gene search in the MN SLE family collection. This will be accomplished by sharing ongoing genotyping data with our colleagues at OMRF (project #2) to compare results in the two SLE family collections. Preliminary mapping results at MN will also be shared with our colleagues at UAB (project #3) to assist in their screening of Chromosome 1q candidate genes. The MN family collection will then be genotyped with markers from the OMRF study, so that linkage results can be directly compared. Interesting chromosomal regions ill then be prioritized for high density marker screens and fine mapping. Trio families (one SLE patient with both parents) collected as a component of this SCOR application will be used in disequilibrium mapping in the targeted areas. A variety of strategies will then be employed to identify the SLE gene(s) in these regions. The ultimate isolation and cloning of SLE genes will provide the first opportunity to understand at the genetic level the defects that lead to the clinical immune dysregulation characteristic of patients with lupus. These insights should suggest new avenues of treatments for this patients, including the potential for somatic gene therapy. Interestingly, lupus- prone families also have an increased incidence of other autoimmune diseases including rheumatoid arthritis, thyroid disease, and diabetes. Thus, the identification of genes that cause human SLE is likely to improve our understanding of the genetics and pathophysiology of organ- specific autoimmunity.