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Reference: Dunham, Ian., (1988). Molecular mapping of the human major histocompatibility complex. DPhil. University of Oxford.Citable link to this page:


Molecular mapping of the human major histocompatibility complex

Abstract: 1. Pulsed field gel electrophoresis (PFGE) and cosmid walking have beenused to establish a molecular map of the human major histocompatibilitycomplex (MHC). Single copy hybridisation probes were isolated fromclusters of cosmid clones, one containing the C2, factor B, C4 and21-hydroxylase genes, and the other containing the genes for tumournecrosis factors (TNF) a and B. These probes and HLA class I and classII gene probes were hybridised to Southern blots of genomic DNA whichhad been digested with infrequently cutting restriction endonucleasesand separated by PFGE. The data obtained allowed the construction of along range genomic restriction map, indicating the MHC spans 3800 kb.This map orients the complement gene cluster with respect to DRA, the C2gene being telomeric to the 21-hydroxylase B gene. In addition, thepositions of the TNF genes were defined. The DRA and 21-hydroxylase Bgenes are separated by no greater than 390 kb, while the distancebetween the C2 and TNFA genes is 325 kb. The HLA-B locus lies about250-300kb telomeric of the TNFB gene.2. The long range DNA organisation of the class II and class III regionsin eight HLA homozygous cell lines has been analysed using PFGE.Comparison of the size of the BssHII restriction fragment observed forthese cell lines and five individuals possessing one to three C4 genes,shows that the organisation of the C4 genes on each chromosome can bededuced from a single PFGE experiment. Outside of the C4 and 21-OHaseloci the class III region shows a highly invariant structure, with nodetectable differences in the amount of DNA present. Moreover the classIII region is rich in CpG-islands, one of which has been characterised,and contains at least thirteen new genes. However, in the class IIregion, two differences between common haplotypes have been found. TheDRw52-related haplotypes have the same DNA organisation. DR2 haplotypespossess 20-30 kb more DNA in the DRB region. DRw53 haplotypes have100-130 kb more DNA than DRw52-related haplotypes in the regioncontaining the DRB and DQA genes.

Type of Award:DPhil Level of Award:Doctoral Awarding Institution: University of Oxford Notes:The digital copy of this thesis has been made available thanks to the generosity of Dr Leonard Polonsky


Campbell, R. DuncanMore by this contributor



Duncan CampbellMore by this contributor


 Bibliographic Details

Issue Date: 1988Identifiers

Urn: uuid:61559181-d77f-479e-8bfe-2e324d8806bd

Source identifier: 602835277 Item Description

Type: Thesis;

Language: eng Subjects: Major histocompatibility complex Genetic aspects Gene mapping Tiny URL: td:602835277


Autor: Dunham, Ian. - institutionUniversity of Oxford facultyLife and Environmental Sciences Division - - - - Contributors Campbell, R.



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