GENETIC LINKAGE IN LUPUS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征是产生针对细胞内抗原的自身抗体。正在收集多病例SLE家族。到目前为止，已经收集了200多个家庭，其中30%是非洲裔美国人（AA），并进行了全基因组扫描。SLE患者的临床表现有相当大的差异，几乎任何器官系统都可能受到影响。关于所观察到的临床变异性是否是由于环境影响、SLE位点的异质性或修饰基因引起的，目前还知之甚少。在最近发表的一项确认研究中，我们已经证实，在有一名受影响男性的家庭中，受影响女性的肾脏疾病发病率高于无受影响男性的家庭中受影响女性的肾脏疾病发病率，这表明这两种类型的家庭可能在遗传上不同。我们已经定位了一个信号，这些家庭在13号染色体上的AA子集。我们还证实，在一个新的收集的高加索家庭，连锁4p 16，并确定了可能的上位性之间的区域和染色体2，12和19。SNP分型刚刚完成了几个候选区域和基因。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Systemic lupus erythematosys (SLE) is an autoimmune disorder characterized by the production of auto-antibodies against intracellular antigens. Collection of multicase SLE families is ongoing. Over 200 families, of which 30% are African-American (AA), have been collected to date and subjected to genome-wide scanning for linked loci. There is considerable variability among SLE patients with respect to the clinical manifestations of disease and virtually any organ system may be affected. Little is known about whether the observed clinical variability is due to environmental effects, heterogeneity of SLE loci, or modifying genes. In a confirmation study, recently published, we have verified that affected females in families with an affected male have a higher incidence of renal disease than affected females in families with no affected male, suggesting that these two types of families may be genetically distinct. We have localized a signal specific to these familes in an AA subset on chromosome 13. We have also confirmed, in a new collection of Caucasian families, linkage to 4p16 and have identified possible epistasis between this and regions on chromosomes 2, 12, and 19. SNP typing has just been completed for several candidate regions and genes.