Yip, Shea Ping;
(1997)
Studies of intragenic recombination in human phosphoglucomutase PGM1.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Human phosphoglucomutase PGMl is a highly polymorphic protein. Four common alleles, 1 + , 1-, 2+ and 2-, are generated by two point mutations and intragenic recombination. The mutation sites are 18 kb apart: one in exon 4 leads to the 2/1 polymorphism and the other in exon 8 accounts for the +/- polymorphism. The main aim of this study was to investigate intragenic recombination in the human PGMl locus using a population-based approach. Sixteen PCR-amplified fragments between the 2/1 and +/- mutation sites were screened for nucleotide polymorphisms using single stranded conformation polymorphism (SSCP) analysis. Six new markers were identified and characterized sequentially in a systematic manner: one in intron 4, three in intron 6 and two in intron 7. In each case, samples from four populations (Caucasian, Chinese, Vietnamese and New Guinean) were typed, family studies were performed and the molecular basis was determined. The population data were analyzed in terms of allelic association, linkage disequilibrium parameters (D and O') and haplotype diversity. This population-based approach localized a recombination site (site A) to a 0.75 kb interval bounded by two markers flanking exon 7. The locus was also examined upstream of the 2/1 polymorphism in order to explore recombination between exons lA and 4. Seven PCR-amplified fragments were examined by SSCP analysis and one new marker was identified in the 5' end of intron 1. The same population-based approach confirmed the existence of a second recombination site (site B) between exons lA and 4. Examination of CEPH families identified four recombinant chromosomes and confirmed that sites A and B are recombination hotspots. Direct sequencing around the hotspot at site A showed no features indicative of genetic instability. But sequence homology analysis identified a potential recombination signal sequence in the gene.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Studies of intragenic recombination in human phosphoglucomutase PGM1 |
| 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/10099375 |
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