کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6803075 | 1433521 | 2018 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ultradeep mapping of neuronal mitochondrial deletions in Parkinson's disease
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Mitochondrial DNA (mtDNA) deletions accumulate with age in postmitotic cells and are associated with aging and neurodegenerative disorders such as Parkinson's disease. Although the exact mechanisms by which deletions form remain elusive, the dominant theory is that they arise spontaneously at microhomologous sites and undergo clonal expansion. We characterize mtDNA deletions at unprecedented resolution in individual substantia nigra neurons from individuals with Parkinson's disease, using ultradeep sequencing. We show that the number of deleted mtDNA species per neuron is substantially higher than previously reported. Moreover, each deleted mtDNA species shows significant differences in sequence composition compared with the remaining mtDNA population, which is highly consistent with independent segregation and clonal expansion. Deletion breakpoints occur consistently in regions of sequence homology, which may be direct or interrupted stretches of tandem repeats. While our results support a crucial role for misannealing in deletion generation, we find no overrepresentation of the 3â²-repeat sequence, an observation that is difficult to reconcile with the current view of replication errors as the source of mtDNA deletions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 63, March 2018, Pages 120-127
Journal: Neurobiology of Aging - Volume 63, March 2018, Pages 120-127
نویسندگان
Gonzalo S. Nido, Christian Dölle, Irene Flønes, Helen A. Tuppen, Guido Alves, Ole-Bjørn Tysnes, Kristoffer Haugarvoll, Charalampos Tzoulis,