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dc.contributor.authorLilley, Rebbecca Catherine
dc.date.accessioned2011-08-31T05:06:49Z
dc.date.available2011-08-31T05:06:49Z
dc.date.issued1996
dc.identifier.urihttps://hdl.handle.net/10182/3822
dc.description.abstractCathepsin B is a lysosomal cysteine protease whose activity has been implicated in a variety of physiological and pathological states including the development of lung disease and the progression of cancers. Cathepsin B has been implicated in the pathogenesis such lung diseases as emphysema and chronic bronchitis. Although no direct associations between cathepsin B and cystic fibrosis are evident, cathepsin B may be implicated to the disease progression through the diseases associated elevation in neutrophil elastase activity. The expression, post translational processing and targeting of cathepsin B is frequently altered in transformed and malignant cancer cells. Associations between malignancy and cathepsin B have been reported for human colon, breast, prostrate and bladder tumours (Keppler and Sloane, 1996). Cathepsin B could have a role in the detachment of cancerous cells from the tumour, and lead hence into metastasis. MacKenzie (1995) identified a 19 nucleotide insertion within intron 7 of the human cathepsin B gene. Sequencing of a B allele also revealed a nucleotide substitution of G to C at position 319 in intron 7. This study reports that this substitution occurs in all B allele homozygotes tested and that polymorphic linkage is present between the absence of the 19 nucleotide insertion and the nucleotide substitution within the B allele. This study also reports the screening of 19 normal DNA samples, 30 DNA samples from cystic fibrosis patients, and 22 colon carcinoma tissue DNA samples (all samples unrelated). A allele frequencies were determined to be 0.62, 0.65, & 0.64 respectively. Chi-square analysis revealed no significant (p=0.99) difference between normal, cystic fibrosis and colon cancer sample populations. The two alleles have been shown to conform to Hardy-Weinberg population distribution within each sample population so are thought to be stably inherited according to Mendalian segregation. Studies have indicated that cathepsin B has multiple forms generated by different cell processing of RNA and glycosylation of the precursor protein. These polymorphisms have been shown to introduce a potential alternative splicing site within intron 7 which, if functional would produce larger sized mRNA. These polymorphisms also have the potential to interfere with the existing intron 7/exon 8 splicing site. This study reports the development of a RNA extraction technique from human blood, and the design and partial optimisation of reverse transcriptase-PCR CRT-PCR). These techniques will be used in the future to study mRNA derived from homozygote individuals blood, and observe any differences in the length or amount of mRNA between the 2 alleles.en
dc.language.isoenen
dc.publisherLincoln Universityen
dc.rights.urihttps://researcharchive.lincoln.ac.nz/page/rights
dc.subjectcathepsin Ben
dc.subjectproteaseen
dc.subjectpolymorphismen
dc.subjectmRNAen
dc.subjectallelesen
dc.titleInvestigation of polymorphic variation within intron 7 of the human cathepsin B geneen
dc.typeDissertationen
thesis.degree.grantorLincoln Universityen
thesis.degree.levelOtheren
thesis.degree.nameBachelor of Scienceen
lu.thesis.supervisorMason, Sue
lu.thesis.supervisorBickerstaffe, Roy
lu.contributor.unitDepartment of Wine, Food and Molecular Biosciencesen
dc.rights.accessRightsDigital thesis can be viewed by current staff and students of Lincoln University only.en
dc.subject.anzsrc0604 Geneticsen
dc.subject.anzsrc060101 Analytical Biochemistryen


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