Genomic Context Analysis of de Novo STXBP1 Mutations Identifies Evidence of Splice Site DNA-Motif Associated Hotspots.
| Autor: | Uddin M; Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, 505055 Dubai, United Arab Emirates 505055, mohammed.uddin@mbru.ac.ae Stephen.Scherer@sickkids.ca.; The Centre for Applied Genomics., Woodbury-Smith M; The Centre for Applied Genomics.; Institute of Neuroscience NE2 4HH is the postal code, Newcastle University, Newcastle upon Tyne, United Kingdom., Chan AJS; The Centre for Applied Genomics.; Program in Genetics and Genome Biology.; Department of Molecular Genetics and., Albanna A; Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, 505055 Dubai, United Arab Emirates 505055.; Division of Neurology, BC Children's Hospital, Vancouver, BC, Canada V6H 3N1, and., Minassian B; Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates PO Box: 76662., Boelman C; Division of Neurology, and., Scherer SW; The Centre for Applied Genomics, mohammed.uddin@mbru.ac.ae Stephen.Scherer@sickkids.ca.; Program in Genetics and Genome Biology.; Department of Molecular Genetics and.; McLaughlin Centre, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8. |
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| Jazyk: | angličtina |
| Zdroj: | G3 (Bethesda, Md.) [G3 (Bethesda)] 2018 Mar 28; Vol. 8 (4), pp. 1115-1118. Date of Electronic Publication: 2018 Mar 28. |
| DOI: | 10.1534/g3.118.200080 |
| Abstrakt: | Mutations within STXBP1 have been associated with a range of neurodevelopmental disorders implicating the pleotropic impact of this gene. Although the frequency of de novo mutations within STXBP1 for selective cohorts with early onset epileptic encephalopathy is more than 1%, there is no evidence for a hotspot within the gene. In this study, we analyzed the genomic context of de novo STXBP1 mutations to examine whether certain motifs indicated a greater risk of mutation. Through a comprehensive context analysis of 136 de novo /rare mutation (SNV/Indels) sites in this gene, strikingly 26.92% of all SNV mutations occurred within 5bp upstream or downstream of a 'GTA' motif ( P < 0.0005). This implies a genomic context modulated mutagenesis. Moreover, 51.85% (14 out of 27) of the 'GTA' mutations are splicing compared to 14.70% (20 out of 136) of all reported mutations within STXBP1 We also noted that 11 of these 14 'GTA' associated mutations are de novo in origin. Our analysis provides strong evidence of DNA motif modulated mutagenesis for STXBP1 de novo splicing mutations. (Copyright © 2018 Uddin et al.) |
| Databáze: | MEDLINE |
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