Hanson, Isabel Mary; (1991) Novel genes in the class I region of the human major histocompatibility complex. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The aim of the work described in this thesis was to identify and characterise novel genes in the class II region of the human major histocompatibility complex (MHC). A physical map of the region, spanning over IMbp, was constructed using pulsed field gel electrophoresis (PFGE) in conjunction with probes for the known class II genes. This map facilitated the direct localisation of the gene for the a2 chain of type XI fibrillar collagen, COL11A2, to a region just centromeric of the class II DP subregion. In addition the PFGE map revealed four clusters of sites for restriction endonucleases which cut preferentially in CpG-rich regions often found at the 5' ends of genes. Three of these clusters were cloned by cosmid walking and chromosome jumping. Genomic fragments from these regions were hybridised to cDNA libraries which resulted in the identification of five novel genes designated RINGl-5. RING1, RING2 and RINGS were 95kb, 90kb and 85kb proximal respectively to DPB2. RINGS was 35kb distal to DNA. RING4 was 25kb proximal to DOB. Nucleotide sequencing revealed that RINGl-5 were not related to each other or to the class II genes. The predicted protein product of RING1 contained a novel cysteine-histidine motif which was conserved in a variety of other proteins and which was reminiscent of domains found in zinc-dependent nucleic acid binding proteins. RINGS potentially encoded a protein with striking homology to the product of fsh, a Drosophila developmental gene. The putative product of RING4 was a member of the 'ABC superfamily of ATP-dependent transporter proteins. RINGS was the human homologue of KE4, a gene in the mouse MHC region which is a candidate for the developmental lethal These findings may be of importance in understanding MHC/disease associations and the role of the MHC in the immune response.

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