INVESTIGATIONS OF HUMAN COMPLEMENT

计划中的研究的主要目标是进一步定义 蛋白质对补体系统的遗传控制。此外， 计划开展的工作旨在研究C2、BF、C4a、C4b、21-OHA的遗传变异 和21-OHB及相关DNA At定义总大小、基因拷贝数、 基因顺序，以及III型MHC的缺失和插入程度 扩展的和非扩展的MHC单倍型区域。我们假设 至少30%的正常高加索人MHC单倍型的DNA固定在 在包括III类基因在内的人类白细胞抗原-B-DR间期最低，因此 在没有血缘关系的人身上，它们的独立例子非常相似。我们 进一步假设正是这些固定的或延伸的单倍型 提供大多数处于连锁不平衡和 多种疾病的许多MHC标志物，包括I型 糖尿病、谷蛋白敏感型肠病、寻常型天疱疮和 先天性肾上腺增生症21-羟基酶缺乏症。在建议的 工作中，我们试图确定哪些特定的限制片段 发现了C2、BF和C4基因的长度多态和序列变异 关于特定的扩展单倍型。我们也希望使用这些标记来 定义“新的”扩展单倍型和它们的一般片段 人口。最后，我们计划尝试解释进化和遗传 相对罕见的变异型单倍型的起源机制 补语的第二个成分，C2 B。

The chief objective of the planned research is the further definition of the genetic control of proteins on the complement system. In addition, the work planned seeks to study genetic variation in C2, BF, C4A, C4B, 21-OHA and 21-OHB and related DNA at define the overall size, gene copy number, gene order, and the extent of deletions and insertions in the class III MHC regions of extended and non-extended MHC haplotypes. We have postulated that at least 30% of normal caucasian MHC haplotypes have fixed DNA at least over the HLA-B-DR interval, including the class III genes, so that independent examples of them in unrelated persons are highly similar. We further postulate that it is these fixed or extended haplotypes that provide most of the HLA allele pairs that are in linkage disequilibrium and many of the MHC markers for a wide variety of diseases, including type I diabetes mellitus, gluten-sensitive enteropathy, pemphigus vulgaris, and 21-hydroxylase deficiency congenital adrenal hyperplasia. In the proposed work, we seek to determine which of the specific restriction fragment length polymorphisms and sequence variants in C2, BF, and C4 gene are found on specific extended haplotypes. We wish also to use these markers to define "new" extended haplotypes and fragments of them in the general population. Finally, we plan to try to explain the evolution and genetic mechanisms of origin of haplotypes with the relatively rare variant of the second component of complement, C2 B.