KAMAT, M.A., 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.Full text not available from this repository.
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.
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|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|
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