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Title: The isolation and characterization of human minisatellite loci
Author: Armour, John Anthony
ISNI:       0000 0001 3427 5393
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1990
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Hypervariable minisatellite regions of human DNA are of considerable interest, not only as highly informative genetic systems, but also as intermediately sized regions of tandem repetition. Methods for the isolation of minisatellite loci from the human genome have been investigated, and 23 new hypervariable loci cloned from an ordered array Charomid library. This method not only allows very efficient isolation of human minisatellites, but can also be used to observe the degree of overlap between multi-locus DNA fingerprinting probes. The 23 new loci have a mean heterozygosity level of 71%, and have been characterized and mapped in the genome. The genomic disposition of human minisatellites has been analysed by investigation of cloned examples. The minisatellites studied show a strong tendency to cluster near the ends of chromosomes, and sequence analysis demonstrates a significant excess of dispersed repeat elements in the DNA flanking human minisatellites. Minisatellite variant repeat (MVR) mapping has also been used to investigate the internal structure of minisatellite alleles. Somatic allele length mutation events have been demonstrated in DNA from colorectal adenocarcinomas, and the mutations observed show many features of general similarity to germline mutation events. A series of human breast tumours has been screened for somatic change, using both multi-locus DNA fingerprinting probes and single-locus minisatellite probes. Somatic change in breast cancers is much less frequent than in colorectal tumours, but some allele losses and mutations have been defined, including a highly unusual mutation, which may be the result of a minisatellite transposition event. Finally, evolution at minisatellite loci has been studied, both by examination of allelic states in current human populations, as well as comparison with non-human primates.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: DNA fingerprinting