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Kamat, M.A., Baccola, A., Cooper, D.N. and Chuzhanova, N. 
ORCID: 0000-0002-4655-3618,
2016.
A role for non-B DNA forming sequences in mediating microlesions causing human inherited disease.
Human Mutation, 37 (1), pp. 65-73.
ISSN 1059-7794
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Abstract
Missense/nonsense mutations and micro-deletions/micro-insertions of <21bp together represent ~76% of all mutations causing human inherited disease. Previous studies have shown that their occurrence is influenced by sequences capable of non-B DNA formation (direct, inverted and mirror repeats; G-quartets). We found that a greater than expected proportion (~21%) of both micro-deletions and micro-insertions occur within direct repeats and are explicable by slipped misalignment. A novel mutational mechanism, non-B DNA triplex formation followed by DNA repair, is proposed to explain ~5 % of micro-deletions and micro-insertions at mirror repeats. Further, G-quadruplex-forming sequences, direct and inverted repeats appear to play a prominent role in mediating missense mutations, whereas only direct and inverted repeats mediate nonsense mutations. We suggest a mutational mechanism involving slipped strand mispairing, slipped structure formation and DNA repair, to explain ~15% of missense and ~12% of nonsense mutations leading to the formation of perfect direct repeat s from imperfect repeats, or to the extension of existing direct repeats. Similar proportions of missense and nonsense mutations were explicable by the mechanism of hairpin loop formation and DNA repair leading to the formation of perfect inverted repeats from imperfect repeats. The proposed mechanisms provide new insights into mutagenesis underlying pathogenic micro-lesions.
| Item Type: | Journal article | ||||||
|---|---|---|---|---|---|---|---|
| Alternative Title: | A role for non-B DNA forming sequences in mediating micro-lesions causing human inherited disease | ||||||
| Publication Title: | Human Mutation | ||||||
| Creators: | Kamat, M.A., Baccola, A., Cooper, D.N. and Chuzhanova, N. | ||||||
| Publisher: | John Wiley | ||||||
| Place of Publication: | Hoboken, NJ, United States | ||||||
| Date: | January 2016 | ||||||
| Volume: | 37 | ||||||
| Number: | 1 | ||||||
| ISSN: | 1059-7794 | ||||||
| Identifiers: |
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| Divisions: | Schools > School of Science and Technology | ||||||
| Record created by: | EPrints Services | ||||||
| Date Added: | 28 Oct 2015 10:34 | ||||||
| Last Modified: | 17 Jan 2020 11:19 | ||||||
| URI: | https://irep.ntu.ac.uk/id/eprint/25908 |
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