MOLECULAR GENETICS OF HUMAN MHC CLASS III REGION

邻近的人类补体C4和类固醇 21-羟化酶（CYP 21）基因的侧翼是新基因RP和基因X。 RP-C4-CYP 21-基因X主要形成称为RCCX的模块结构， 组织相容性复合物（MHC）。 在数量上有变化 和RCCX模块在人群中的结构。 缺陷 RCCX中的功能基因可能导致遗传和/或自身免疫性 缺陷 通过分子生物学方法，发现了三组移动的遗传元件， 我们在RCCX模块：内源性逆转录病毒HERV-K（C4）， 介导C4基因的大小变异，八个Alu元件，和一个 一组新的复合重复DN形成了一个离散的遗传 RP 1基因中的SVA元件。 在此建议充分 描述人群中RCCX模块化结构，分析 180 Kb的DNA序列跨越了十多个人类基因， 疾病标志物和突变。 这项研究将扩大到 HERV-K（C4）的38个成员，以及人类中的复合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， 通过多重序列比对进行序列分析， 数据库检索是本研究的重要组成部分。 PSC的设备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.