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Genomic organisation and transcript identification in the class II region of the human major histocompatibility complex

Jackson, Amanda; (1995) Genomic organisation and transcript identification in the class II region of the human major histocompatibility complex. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The aim of the work described in this thesis was to provide a complete picture of the class II region of the human major histocompatibility complex (MHC), identifying all the genes present, their genomic organisation and function. Completion of the class II cosmid map was achieved by cloning two remaining regions: 1) 40 kb of the DNA between the DMB and LMP2 genes and 2) 24 kb of the DNA between the genes DPA1 and DNA. This map facilitated the localisation of a retinoid receptor ? gene, hRXR?, 60 kb centromeric of DPB2 and eight cDNAs, one of which encoded a pseudogene with homology to a rabbit muscle phosphatase inhibitor-2 (IPP-2) gene. Exon amplification revealed two exons within 2.2 kb centromeric of DMB which could be alternate splice products of the DMB gene. Three cDNAs composed of two exons and one intron, mapping between the DMB and LMP2 genes, were isolated from cDNA libraries. The three transcripts were not detectable on northern blots. Four unspliced transcripts contiguous with genomic DNA from within the class II region, were present in cDNA libraries. All seven transcripts probably result from aberrant mRNA transcription. Screening and partial sequencing of cosmids covering the class II region identified no other transcripts between DPB2 and DRB1. Experiments were designed to investigate the evolutionary origins of the TAP and LMP genes. To this end, LMP-related genes on other chromosomes were investigated for linkage to TAP-related sequences. Three cDNAs were identified, mapping within 12 kb of the LMP7-related gene, MB1, on chromosome 14. No sequence homology between the cDNAs and TAP genes was observed. The MB1 gene consisted of three exons and two introns. This organisation is very different from LMP7 which is composed of six exons and five introns. Hence, it is likely that MB1 and LMP7 are separated by considerable evolutionary time.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Genomic organisation and transcript identification in the class II region of the human major histocompatibility complex
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10103772
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