INVESTIGATIONS OF HUMAN COMPLEMENT

计划研究的主要目标是进一步确定 补体系统中蛋白质的遗传控制。 此外该 计划中的工作旨在研究C2、BF、C4 A、C4 B、21-OHA的遗传变异 和21-OHB和相关DNA在定义整体大小，基因拷贝数， 基因顺序，以及III类MHC中缺失和插入的程度 延伸和非延伸的MHC单倍型区域。 我们假设 至少30%的正常高加索人MHC单倍型具有固定的DNA， 至少在HLA-B-DR间期，包括III类基因，因此， 在不相关的人身上的独立例子是高度相似的。 我们 进一步假设，正是这些固定的或扩展的单倍型， 提供了大多数连锁不平衡的HLA等位基因对， 许多MHC标志物用于多种疾病，包括I型， 糖尿病、谷蛋白敏感性肠病、寻常天疱疮，以及 21-羟化酶缺乏性先天性肾上腺皮质增生 拟议 工作，我们试图确定哪个特定的限制性片段 C2、BF和C4基因存在长度多态性和序列变异 特定的扩展单倍型。 我们还希望利用这些标记， 定义“新的”扩展单倍型和它们的片段， 人口 最后，我们计划尝试解释进化和遗传 单倍型的起源机制与相对罕见的变异， 补体的第二成分，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.