MOLECULAR GENETICS OF HUMAN MHC CLASS III REGION

邻近的人类补体C4和类固醇 21-羟基酶(CyP21)基因的两侧是新基因RP和基因X。 Rp-C4-CyP21-基因X形成一种模块化结构，称为RCCX。 组织相容性复合体(MHC)。这个数字有一个变化 和RCCX模块在种群中的结构。的不足之处 RCCX中的功能基因可能导致遗传和/或自身免疫 缺陷。已经发现了三组可移动的遗传元件 美国在RCCX模块：一种内源性逆转录病毒HERV-K(C4)，它 介导C4基因、8个Alu元素和a 构成离散遗传的一组新的复合重复DN 单位，即RP1基因中的SVA元件。在此建议充分考虑 描述RCCX在人群中的模块化结构，以进行分析 通过作图获得跨越十多个人类基因的180kb DNA序列 疾病标记物和突变。这项研究将扩展到 HERV-K(C4)的38个成员及其在人类中的复合型SVA 基因组。共同的主题是阐明导致 MHC的遗传不稳定性。DNA序列的测定， 通过多序列比对和多序列比对分析序列 数据库搜索是本研究最重要的组成部分。 PSC的设施和软件使我们能够分析复杂的 RCCX的结构和大量的序列信息 有效地。

The neighboring human complement C4 and steroid 21-hydroxylase(CYP21) genes are flanked by novel genes RP and Gene X. RP-C4-CYP21-Gene X form a modular structure termed RCCX in the major histocompatability complex(MHC). There is a variation in the number and structure of RCCX modules in the population. Deficiencies of the functional genes in RCCX may lead to genetic and/or autoimmune defects. Three groups of mobile genetic elements have been found by us at the RCCX modules: an endogenous retrovirus HERV-K(C4) which mediates the size variation of C4 genes, eight Alu elements, and a novel group of composite repetitive DN forming a discrete genetic unit, the SVA element, in the RP1 gene. It is proposed here to fully characterize the RCCX modular structures in the population, to analyze the 180 Kb DNA sequence spanning more than ten human genes by mapping the disease markers and mutations. This research will be extended to the 38 members of HERV-K(C4), and the composite SVA in the human genome. The common theme is to elucidate the mechanisms leading to genetic instabilities of the MHC. Determination of DNA sequences, analysis of sequences through multiple sequence alignments and database searching are the most important component of this research. The facilities and software of PSC enable us to analyze the complex structures of RCCX and large amounts of sequence information effectively.