HUMAN FAS POLYMORPHISM IN DISEASE

描述：（改编自申请人摘要）动物模型 表明不同的遗传因素影响易感性， 自身免疫性疾病和疾病发作的时间。 自身免疫 MRL鼠品系的病症类似于SLE。 的lpr 小鼠Fas基因中的（淋巴增殖性）突变加速了 MRL-lpr/lpr小鼠中狼疮的发作。 有基因的影响， 对人类SLE的易感性 人类狼疮的早期发作也会发生。 虽然没有排除环境加速因素， 遗传成分加速或早发性SLE的建议，其 在某些种族群体中占主导地位。非裔美国人患SLE的年龄为 比美国白种人年轻得多。 除了有 狼疮样疾病MRL-lpr/lpr小鼠也形成了一种独特的 淋巴组织增生性疾病，其在人类中具有对应物， 儿童期发病综合征。 研究人员将检验人类基因多态性 Fas基因易患MRL-lpr/lpr综合征的人类类似物， 早发性SLE和青少年LPR疾病。 具体目标概述 实现这一目标的策略：（1）Fas多态性 与SLE的发病年龄相关 在其他种族群体和青少年lpr疾病中发病？ (2)什么 是a）该Fas多态性的分子基础和B）其 功能相关物？ (3)Fas的遗传方式是什么 多态性？以及（4）人类Fas的基因组结构是如何影响Fas的表达的？ 正常人与SLE及幼年型lpr患者的基因比较 疾病

DESCRIPTION: (Adapted from the applicant's abstract) Animal models demonstrate different genetic factors which influence predisposition to autoimmune disease and the timing of disease onset. The autoimmune disorder of the MRL murine strain resembles SLE. The lpr (lymphoproliferative) mutation in the murine Fas gene accelerates the onset of lupus in MRL-lpr/lpr mice. There are genetic influences on susceptibility to human SLE. Early onset of human lupus also occurs. Although environmental accelerating factors have not been excluded, a genetic component to accelerated or early onset SLE is suggested by its predominance in some ethnic groups.African-Americans develop SLE at a significantly younger age than do U.S. Caucasians. In addition to the lupus-like disease MRL-lpr/lpr mice also develop a unique lymphoproliferative disease which has its human counterpart in a childhood onset syndrome. The investigators will test the hypothesis that polymorphism in the human Fas gene predisposes to the human analogs of MRL-lpr/lpr syndromes, early onset SLE, and juvenile lpr disease. The specific aims outline strategies to accomplish this goal: (1) Does the Fas polymorphism associated with early onset SLE in Blacks correlate with age of SLE onset in other ethnic groups and with juvenile lpr disease? (2) What is the a) the molecular basis for this Fas polymorphism and b) its functional correlate(s)? (3) What is the mode of inheritance of the Fas polymorphism? and (4) How does the genomic organization of the human Fas gene compare in normal individuals and those with SLE and juvenile lpr disease.