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1.
Figure  3. 

Figure 3. . From: Mitochondrial DNA-Deletion Mutations Accumulate Intracellularly to Detrimental Levels in Aged Human Skeletal Muscle Fibers.

Log10 of mtDNA wild-type and partially deleted genomes along the length of fibers 19 (A), 36 (B), 37 (C), and 23 (D). Unblackened circles represent wild-type mtDNA, and blackened circles represent deletion-containing genomes.

Entela Bua, et al. Am J Hum Genet. 2006 September;79(3):469-480.
2.
Figure  2. 

Figure 2. . From: Mitochondrial DNA-Deletion Mutations Accumulate Intracellularly to Detrimental Levels in Aged Human Skeletal Muscle Fibers.

Schematic representation of the human mtDNA-deletion mutations obtained from 48 COX/SDH++ fibers. mtDNA-deletion mutations were detected in all 48 ETS-abnormal fibers, and breakpoints were determined by DNA sequence analysis. Arcs represent the deleted regions of the genome. The location of the light-strand (OL) and the heavy-strand (OH) origins of replication are indicated. Cyt = cytochrome.

Entela Bua, et al. Am J Hum Genet. 2006 September;79(3):469-480.
3.
Figure  1. 

Figure 1. . From: Mitochondrial DNA-Deletion Mutations Accumulate Intracellularly to Detrimental Levels in Aged Human Skeletal Muscle Fibers.

Detection of mtDNA-deletion mutations by major arc mtDNA-genome amplification. Total DNA from microdissected COX/SDH++ fibers was subjected to long-extension PCR. mtDNA-specific primers (F4840–R766) that amplify ∼13 kb of the full-length genome, including two origins of replication, were used. Full-length amplification products were detected in ETS-normal fibers (n). Smaller amplification products were identified in ETS-abnormal fibers (8, 11, 28, 31, and 34). Amplification of total mtDNA from tissue homogenates (T) detected both full-length and smaller amplification products. M = DNA molecular-weight standards.

Entela Bua, et al. Am J Hum Genet. 2006 September;79(3):469-480.
4.
Figure  6. 

Figure 6. . From: Mitochondrial DNA-Deletion Mutations Accumulate Intracellularly to Detrimental Levels in Aged Human Skeletal Muscle Fibers.

Accumulation, with age, of mtDNA4977 and mtDNA7664 deletion mutation in tissue homogenate. A, Primers specific for mtDNA4977 (F8369–R13498) were used to measure the amount of deletion mutation. The wild-type primer set (F12354–R12549) was designed to amplify a region of the genome within the breakpoints of the deleted mtDNA, to ensure that the primers amplified full-length wild-type genomes. The amount of mtDNA4977 deletion mutation had a range of 0.02%–0.06% of the wild-type genomes for ages 49-79 years. The deletion-mutation level significantly increased to 0.1%–0.225% of the wild-type genomes for ages 83–93 years. B, Primers specific for mtDNA7664 (F6256–R14122) were used to measure the amount of deletion mutation. Primer set F12354–R12549 was used to measure the amount of wild-type mtDNA present. The mtDNA7664 deletion mutation load fluctuated between ages 49 and 92 years. A significant (P<.05) increase was found at age 93 years.

Entela Bua, et al. Am J Hum Genet. 2006 September;79(3):469-480.
5.

Figure 4. . From: Mitochondrial DNA-Deletion Mutations Accumulate Intracellularly to Detrimental Levels in Aged Human Skeletal Muscle Fibers.

mtDNA deletion–mutation abundance along the length of COX/SDH++ fibers. LCM was used to isolate 10-μm thick tissue sections at numerous sites along the length of single muscle fibers. Quantitative PCR defined the abundance of full-length and deleted mtDNA. A, B, and C, Percentage of deleted mtDNA7664 in the abnormal region of fibers 19, 36, and 37, respectively. D, Percentage of deleted mtDNA4989 in the abnormal region of fiber 23. a, Photomicrographs of tissue cross-sections sequentially double stained for COX and SDH activity. The individual fiber (arrow) displays an ETS-abnormal phenotype. b, Digital reconstruction of CSA silhouettes. The COX/SDH++ region is shown in dark blue, the COXlow/SDHhigh region in light blue, and the COXnormal/SDHnormal in orange.

Entela Bua, et al. Am J Hum Genet. 2006 September;79(3):469-480.
6.
Figure  5. 

Figure 5. . From: Mitochondrial DNA-Deletion Mutations Accumulate Intracellularly to Detrimental Levels in Aged Human Skeletal Muscle Fibers.

mtDNA4977 deletion mutation in tissue homogenate from aged human skeletal muscle. Total DNA was isolated from skeletal muscle–tissue homogenates of 49-, 60-, 64-, 76-, 83-, and 92-year-old human subjects. To investigate the presence of mtDNA4977 mutations in skeletal muscle–tissue homogenate at different ages, total DNA was subjected to PCR with primers (F8111–R13756) (table 2A) immediately flanking the deleted region. This deletion mutation was present in all analyzed tissue homogenates. In addition, 57 ETS-normal fibers (fibers that exhibited the COXnormal/SDHnormal phenotype throughout 2,000 μm of analyzed tissue) were randomly selected and analyzed for the presence of mtDNA4977 from a 49-year-old subject (20 fibers) and from a 92-year-old subject (37 fibers). mtDNA4977 was not detected in any of these fibers. M = DNA molecular-weight standards; ntc = no template control.

Entela Bua, et al. Am J Hum Genet. 2006 September;79(3):469-480.

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