Splice-Break: exploiting an RNA-seq splice junction algorithm to discover mitochondrial DNA deletion breakpoints and analyses of psychiatric disorders
| العنوان: | Splice-Break: exploiting an RNA-seq splice junction algorithm to discover mitochondrial DNA deletion breakpoints and analyses of psychiatric disorders |
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| المؤلفون: | Marquis P. Vawter, Elizabeth C. Chao, Filipe Pereira, William E. Bunney, Jack D. Barchas, Richard M. Myers, Adolfo Sequeira, Joana Damas, Ling Morgan, Firoza Mamdani, Francis S. Lee, Brooke E. Hjelm, Alan F. Schatzberg, Brandi Rollins, Michelle Webb, Huda Akil, Virginia Kimonis, Matthieu D Weber, Stanley J. Watson, Peter M. Thompson |
| المصدر: | Nucleic Acids Research |
| بيانات النشر: | Oxford University Press (OUP), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Mitochondrial DNA, Sequence analysis, Biology, DNA, Mitochondrial, Polymerase Chain Reaction, Genome, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, law, Genetics, Humans, splice, Polymerase chain reaction, Sequence Deletion, 030304 developmental biology, Depressive Disorder, Major, 0303 health sciences, Base Sequence, Sequence Analysis, RNA, DNA Breaks, Breakpoint, Brain, Computational Biology, RNA, chemistry, Methods Online, Female, RNA Splice Sites, Algorithm, Algorithms, 030217 neurology & neurosurgery, DNA |
| الوصف: | Deletions in the 16.6 kb mitochondrial genome have been implicated in numerous disorders that often display muscular and/or neurological symptoms due to the high-energy demands of these tissues. We describe a catalogue of 4489 putative mitochondrial DNA (mtDNA) deletions, including their frequency and relative read rate, using a combinatorial approach of mitochondria-targeted PCR, next-generation sequencing, bioinformatics, post-hoc filtering, annotation, and validation steps. Our bioinformatics pipeline uses MapSplice, an RNA-seq splice junction detection algorithm, to detect and quantify mtDNA deletion breakpoints rather than mRNA splices. Analyses of 93 samples from postmortem brain and blood found (i) the 4977 bp ‘common deletion’ was neither the most frequent deletion nor the most abundant; (ii) brain contained significantly more deletions than blood; (iii) many high frequency deletions were previously reported in MitoBreak, suggesting they are present at low levels in metabolically active tissues and are not exclusive to individuals with diagnosed mitochondrial pathologies; (iv) many individual deletions (and cumulative metrics) had significant and positive correlations with age and (v) the highest deletion burdens were observed in major depressive disorder brain, at levels greater than Kearns–Sayre Syndrome muscle. Collectively, these data suggest the Splice-Break pipeline can detect and quantify mtDNA deletions at a high level of resolution. |
| تدمد: | 1362-4962 0305-1048 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9fe7ec3f302b0325abcff4bc50f12d5eTest https://doi.org/10.1093/nar/gkz164Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9fe7ec3f302b0325abcff4bc50f12d5e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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