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ALLOZYME VARIATION IN NATURAL POPULATIONS

自然群体中的同种酶变异

基本信息

批准号：
3281553
负责人：
DONALD V CRAMER
金额：
$ 11.8万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-04-01 至 1987-03-31
项目状态：
已结题

项目摘要

The work described in this proposal is designed to examine the degree of genetic polymorphism in a variety of major histocompatibility complex (MHC) linked and non-linked enzyme loci. The objectives of the proposal are (1) to establish whether or not those loci associated with the rat MHC exhibit a higher degree of genetic variation than those coded for by other, non-MHC, linkage groups, (2) to establish the presence or absence of significant linkage disequilibrium between alleles at loci within homologous chromosomal segments shared between rodents and man and, (3) to detect and characterize new enzyme variants potentially linked to the rat MHC (RT1 complex) for use as marker genes in genetic studies of this important complex. The research work will be conducted by systematically screening blood and tissue samples collected from widely-separate populations of wild rats. Multiple sites at each locus compared within the rat populations and to comparable studies in other species. New alloenzyme variants will be characterized and their chromosomal linkage relationships established whenever possible. The research work outlined in this proposal addresses three important problems. The first is whether or not the restricted degree of polymorphism and linkage disequilibrium observed in the rat MHC is unique or are also seen in unrelated linkage groups. The results of these experiments may have a substantial impact on theories that relate to the requirement for high levels of polymorphism to explain the function of the MHC. Secondly, we seek to determine if linkage disequilibrium can be invoked as a mechanism to explain the retension of homologous chromosomal segments. The retension of large, homologous chromosomal segments between species is well recognized but it remains to be established whether or not these segments are maintained by chance or by active selection. Third the discovery of new variants for enzymes linked to the MHC can be of important use in establishing the structure and gene order of loci within the RTl complex of the rat.

本提案中描述的工作旨在检查多种主要组织相容性复合体(MHC)的遗传多态性连锁和非连锁酶基因座。该提案的目标是(1) 以确定这些与大鼠MHC相关的基因座是否表现出比其他基因编码的基因变异程度更高，非MHC，连接基，(2)确定存在或不存在基因座上的等位基因间存在显著连锁不平衡啮齿动物和人类之间共享的同源染色体片段和，(3)到检测和鉴定可能与大鼠相关的新酶变体 MHC(rt1复合体)作为标记基因用于本病的遗传学研究重要的情结。研究工作将以系统的方式进行对广泛分离的血液和组织样本进行筛查成群的野鼠。每个位置上的多个站点在老鼠种群和其他物种中的可比研究。新型同种异构酶变异的特征和它们的染色体连锁关系只要有可能就建立起来。这项提案中概述的研究工作解决了三个重要问题。第一个问题是，观察到的多态和连锁不平衡的限制程度大鼠MHC是独一无二的，或者也可以在不相关的连锁群中看到。这个这些实验的结果可能会对以下理论产生重大影响与对高水平多态的要求有关，以解释 MHC的功能。其次，我们试图确定是否存在关联不平衡可以作为一种机制来解释同源染色体片段。大的、同源的保持力物种之间的染色体片段已经被很好地识别了，但它仍然是确定这些段是偶然维护的还是由主动选择。第三，发现与酶相关的新变种对于建立MHC的结构和基因具有重要的作用大鼠RTL复合体内基因座的顺序。