The Isolation and Characterisation of Mouse Genes Containing CAG/CTG Trinucleotide Repeats

Dunlop, Thomas William (1997) The Isolation and Characterisation of Mouse Genes Containing CAG/CTG Trinucleotide Repeats. PhD thesis, University of Glasgow.

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Triplet repeats are simple tandem repeats with a basic unit of three nucleotides. The CTG/CAG class, which is over-represented in higher eukaryote genomes, occurs in a number of regulatory genes, often encoding poly-glutamine. More recently, expansion of CAG/CTG triplet repeats in certain human genes has become associated with certain diseases, leading either to loss of function (as the case may be with CTG in Myotonic Dystrophy) or gain of function (CAG encoding glutamine stretches in SCA1 , Huntington's disease, Kennedy's Disease). Since the mouse is the best mammalian organism in which to study the biology of triplet repeats and the genes in which they occur, a set of mouse cDNAs containing triplet repeats was isolated and partially characterised. To this end, DNA sequencing was performed to identify the trinucleotide repeats. Sequences flanking the trinucleotide repeat were used to identify genes which show similarity or identity to previously characterised genes. This was used to compare the lengths of the trinucleotide repeats found in the mouse clones described in this work with those found in (previously characterised) genes which have trinucleotide repeats at identical positions. To identify clones which showed changes to mR N A abundance during development and adult tissue, reverse dot-blot analysis was performed on a subset of cDNA clones derived from the 8.5 and 12.5 dpc whole mouse embryo cDNA libraries. Finally, four clones (two high and two low RNA abundance) were selected for further molecular analysis. Of these four clones, the two which exhibited high levels of RNA in the reverse dot blot experiments, showed a more complex expression pattern in northern analysis and all four clones appear to derive from single copy (per haploid genome) genes. In conclusion, this work has indicated that mouse genes contained similarly sized trinucleotide repeats compared to those found in human genes; that these repeats are possibly conserved between distantly related species and this may be related to the proper function of the genes. A third of those genes (which were analysed for the existence of RNA derived from the parental gene) displayed detectable amounts of expression and most showed variations in the RNA abundance either at different stages during development or in different adult tissues. Most of those were derived from unknown genes. This indicates that there may be many novel genes containing CAG/CTG trinucleotide in the mouse which may be identified in the future for further characterisation during developmental and organ specific analysis. One clone (mCTG 63), although not novel, contains the largest perfect CAG/CTG triplet repeat found in this work. The repeat may be transcribed as (TG in the coding strand of this gene. This situation is analogous to the CTG triplet repeat which has a role in myotonic dystrophy (found in the 3'UTR of the DMPK gene). This clone is worth further analysis for this reason.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Wayne R Davies
Keywords: Genetics
Date of Award: 1997
Depositing User: Enlighten Team
Unique ID: glathesis:1997-74662
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 27 Sep 2019 17:18
Last Modified: 27 Sep 2019 17:18

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