کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10737281 | 1046375 | 2005 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Contribution of de novo point mutations to the overall mutational burden in mitochondrial DNA of adult rats
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Contribution of de novo point mutations to the overall mutational burden in mitochondrial DNA of adult rats Contribution of de novo point mutations to the overall mutational burden in mitochondrial DNA of adult rats](/preview/png/10737281.png)
چکیده انگلیسی
This study analyzed the incidence of point mutations in mitochondrial DNA of brain and muscle tissues from young (6-month) and old (24-month) male F344 rats. Coding sequence mutations in subunit 5 of the NADH dehydrogenase gene were detected after high-fidelity PCR amplification and cloning by denaturing gradient gel electrophoresis (DGGE) assay followed by sequencing of detected mutants. In total, almost a thousand individual clones were analyzed both in brain and muscle samples. On average, mtDNA from brain tissue showed a 66% increase with age in mutation frequencies (2.3±1.9 vs. 3.8±4.5Ã10â4 mutations/bp, mean±SD), which failed to reach statistical significance (p=0.45). Muscle tissues yielded substantially fewer mutants with average mutant frequencies for both young and old rats almost 10 times lower than the corresponding values in the brain tissue (0.3±0.4 and 0.5±0.6Ã10â4, respectively). The difference in mutation accumulation between muscle and brain was highly significant in both the younger group (Chi-squared=9.7, pâ¤0.01) and in older animals (Chi-squared=10.9, pâ¤0.001). Molecular analysis of the mutated sequences revealed that almost half were identical sequences recurring in different samples and tissues. Our findings indicate that the process of mutation accumulation in mitochondria begins in the germ-line and/or during earlier stages of life, contributing up to half of the total mutational burden, whereas de novo spontaneous formation of point mutations in adulthood is far less than was anticipated.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Gerontology - Volume 40, Issue 5, May 2005, Pages 396-402
Journal: Experimental Gerontology - Volume 40, Issue 5, May 2005, Pages 396-402
نویسندگان
M. Khaidakov, N. Chavannes-Turesky, C.A. Cooney, E.E. Dupont-Versteegden, R.H. Kennedy, E.R. Siegel, G. Khaidakova, R.J. Shmookler Reis,