The involvement of non-B DNA forming sequences in mediating missense mutations, micro-deletions and micro-insertions in human inherited disease

Kamat, MA, 2014. The involvement of non-B DNA forming sequences in mediating missense mutations, micro-deletions and micro-insertions in human inherited disease. PhD, Nottingham Trent University.

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Abstract

The involvement of the local DNA sequence features (repetitive elements capable of adopting non-B structures, hotspot motifs, mononucleotide runs and tandem repeats) and epigenetic marks in mediating germline missense and nonsense mutations, micro-deletions and micro-insertions causing human inherited disease and obtained from Human Gene Mutation Database (HGMD; http://www.hgmd.org) was studied in silico. A novel algorithm with a linear running time has been designed to detect the non-B DNA forming repeats in DNA sequences. The distributions of these repeats in the vicinity of mutations were analysed. We found that ~15% of missense mutations, ~12% of nonsense mutations, ~28% of micro-deletions and ~21% of micro-insertions occurred within direct repeats and is explicable by the formation/resolution/correction of non-B slipped structures. Several novel mutational mechanisms such as slipped strand mispairing/non-B slipped structure formation/DNA repair, non-B triplex formation/DNA repair and hairpin loop formation/DNA repair mechanisms have been proposed to explain single basepair substitutions leading to the formation of respectively exact direct, mirror and inverted repeats from inexact repeats. The role of CpG dinucleotides, CpHpG trinucleotides in mediating single base-pair substitutions and 83 known hotspot motifs together with other repetitive elements was studied in the context of micro-deletions and micro-insertions.

Item Type: Thesis
Description: The full text of this thesis is not available due to restrictions placed by the author, use of copyrighted material, or patents pending.
Creators: Kamat, M.A.
Date: 2014
Rights: This work is the intellectual property of the author. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed to the owner(s) of the Intellectual Property Rights.
Divisions: Schools > School of Science and Technology
Depositing User: EPrints Services
Date Added: 09 Oct 2015 09:49
Last Modified: 09 Oct 2015 09:49
URI: http://irep.ntu.ac.uk/id/eprint/3366

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