HUMAN FAS POLYMORPHISM IN DISEASE

描述：(改编自申请者摘要)动物模型 展示影响易感性的不同遗传因素 自身免疫性疾病和疾病发病的时间。自身免疫 MRL小鼠品系的紊乱类似于SLE。LPR 小鼠Fas基因(淋巴增殖性)突变加速 MRL-lpr/lpr小鼠狼疮的发病情况。有遗传因素的影响 对人类系统性红斑狼疮易感性。人类狼疮的早期发病也会发生。 尽管环境加速因素没有被排除在外，但一个 加速或早发性系统性红斑狼疮的遗传因素 在一些种族群体中占主导地位。非裔美国人在一种 比美国高加索人年轻得多。除了 狼疮样疾病MRL-LPR/LPR小鼠也发展出一种独特的 一种淋巴增生性疾病，它与人类的 儿童期发病综合征。 研究人员将检验这一假设，即人类的基因多态 Fas基因易患人类类似的MRL-LPR/LPR综合征， 早发性系统性红斑狼疮和幼年性LPR病。具体目标提纲 实现这一目标的策略：(1)Fas多态 黑人早发性系统性红斑狼疮与年龄相关 在其他民族和青少年LPR病中起病？(2)什么 是a)这种Fas多态的分子基础和b)它的 功能相关(S)？(3)Fas的遗传方式是什么 多态？以及(4)人类Fas的基因组组织是如何 正常人、系统性红斑狼疮和青少年LPR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.