Detection of the A189G mtDNA heteroplasmic mutation in relation to age in modern and ancient bones

Lacan, Marie; Thèves, Catherine; Amory, Sylvain; Keyser, Christine; Crubézy, Éric; Salles, Jean‐Pierre; Ludes, Bertrand; Telmon, Norbert

doi:10.1007/s00414-008-0266-y

Cited by 18 publications

(11 citation statements)

References 28 publications

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“…Such "C-tracts" are prone to length heteroplasmy; in other words, one individual can have various mtDNA lengths in his or her cells which differ by the number of C's at these C-tracts [3,20]. Research on the cellular mechanisms and circumstances causing heteroplasmy is ongoing [8,12,14,16,19]. These C-heteroplasmies are not rare, but indeed are typical in the majority of casework.…”

Section: Introductionmentioning

confidence: 97%

Evaluating length heteroplasmy in the human mitochondrial DNA control region

Forster

Gurney

et al. 2009

Int J Legal Med

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We present allelic data for three known and one new C-tract in the human mitochondrial DNA (mtDNA) control region, and we measure intergenerational mutation rates at such C-tracts. In detail, in a sample of 1,172 mtDNA sequences, we demonstrate the existence of an instability threshold of eight consecutive cytosines, at and above which the phenomenon of length heteroplasmy arises. To determine mutation rates, we draw on mtDNA sequences in up to four generations of 248 pedigrees for families living in high or low-radiation environmental conditions. The high-radiation sample gives the most conservative (fastest) mutation rate likely to be encountered in any forensic context. We find that the C-tract mutation rate is up to 6% per generation, and we observe an excess of cytosine gains over losses. Case studies and guidelines for evaluating mtDNA heteroplasmy are provided.

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Section: Introductionmentioning

confidence: 97%

Evaluating length heteroplasmy in the human mitochondrial DNA control region

Forster

Gurney

et al. 2009

Int J Legal Med

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“…In a previous study, we found that one of the most studied point mutations associated with age on muscle tissue (A189G) also accumulates in bone samples of aged individuals [16]. The aim of the present study was to show that the presence of another type of heteroplasmic mutation, the tandem duplications, is also linked with age in human bones.…”

Section: Introductionmentioning

confidence: 89%

“…They were collected during medico-legal autopsies from accidental death victims, secondarily identified. Among these, 29 double bone/muscle samples were extracted and screened for the detection of the A189G heteroplasmic mutation [16]. For the 53 remaining individuals, DNA was extracted from each sample (bone and muscle) with the PrepFiler™ Forensic DNA Extraction Kit (Applied Biosystems, AB, Foster City, CA) according to the manufacturer's instructions and then purified and concentrated with Microcon YM30 filters (Millipore, Billerica, MA, USA).…”

Section: Samples and Extractionmentioning

confidence: 99%

Detection of age-related duplications in mtDNA from human muscles and bones

et al. 2010

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Several studies have demonstrated the age-related accumulation of duplications in the D-loop of mitochondrial DNA (mtDNA) extracted from skeletal muscle. This kind of mutation had not yet been studied in bone. The detection of age-related mutations in bone tissue could help to estimate age at death within the context of legal medicine or/and anthropological identification procedures, when traditional osteological markers studied are absent or inefficient. As we detected an accumulation of a point mutation in mtDNA from an older individual's bones in a previous study, we tried here to identify if three reported duplications (150, 190, 260 bp) accumulate in this type of tissue. We developed a sensitive method which consists in the use of back-to-back primers during amplification followed by an electrophoresis capillary analysis. The aim of this study was to confirm that at least one duplication appears systematically in muscle tissue after the age of 20 and to evaluate the duplication age appearance in bones extracted from the same individuals. We found that the number of duplications increase from 38 years and that at least one duplicated fragment is present in 50% of cases after 70 years in this tissue. These results confirm that several age-related mutations can be detected in the D-loop of mtDNA and open the way for the use of molecular markers for age estimation in forensic and/or anthropological identification.

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“…The fate of heteroplasmic mutations depends on several factors, including the replication rate of the cell, type and location of the variation (DiMauro and Davidzon, 2005;Lacan et al, 2008). Several mutant mtDNA varieties may be present at undetectable low concentrations, and the degree of heteroplasmy may also be tissue-specific.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

The link between mitochondrial DNA hypervariable segment I heteroplasmy and ageing among genetically unrelated Latvians

Pliss

Brakmanis

Ranka

et al. 2011

Experimental Gerontology

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To cite this version:This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractVarious studies have demonstrated that mitochondrial DNA (mtDNA) heteroplasmy tends to increase with age and that the observed frequency of heteroplasmy among populations mostly depends on the way it is measured. Therefore, we investigated age-related association on the presence of mtDNA heteroplasmy within the hypervariable segment 1 (HVS-I) in a selected study group. The study group consisted of 300 maternally unrelated Latvians ranging in age from 18 to over 90 years. To determine the optimal method for mtDNA heteroplasmy detection, three The results indicate that heteroplasmy in HVS-I is relatively common and occurs in a broad spectrum of sites. The above is supported by evidence to eventual increase of the probability of heteroplasmy with age due to specific mitochondrial haplogroup background. Research HighlightsThe results indicate that heteroplasmy in HVS-I is relatively common and occurs in a broad spectrum of sites. Consequently, a strong association is found to exist between the mtDNA heteroplasmy and ageing in the studied population.We found that the Denaturing Gradient Gel Electrophoresis (DGGE) and the SURVEYOR TM Mutation Detection Kit assay exhibited a lower limit of detection (LOD) of mtDNA heteroplasmy and revealed the presence of heteroplasmy at the already existing 1% and 5% occurrence in the sample.

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Detection of the A189G mtDNA heteroplasmic mutation in relation to age in modern and ancient bones

Cited by 18 publications

References 28 publications

Evaluating length heteroplasmy in the human mitochondrial DNA control region

Evaluating length heteroplasmy in the human mitochondrial DNA control region

Detection of age-related duplications in mtDNA from human muscles and bones

The link between mitochondrial DNA hypervariable segment I heteroplasmy and ageing among genetically unrelated Latvians

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