Age-Related and Heteroplasmy-Related Variation in Human mtDNA Copy Number
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{"title"=>"Age-Related and Heteroplasmy-Related Variation in Human mtDNA Copy Number", "type"=>"journal", "authors"=>[{"first_name"=>"Manja", "last_name"=>"Wachsmuth", "scopus_author_id"=>"57199083722"}, {"first_name"=>"Alexander", "last_name"=>"Hübner", "scopus_author_id"=>"57076112600"}, {"first_name"=>"Mingkun", "last_name"=>"Li", "scopus_author_id"=>"36342564500"}, {"first_name"=>"Burkhard", "last_name"=>"Madea", "scopus_author_id"=>"7102211257"}, {"first_name"=>"Mark", "last_name"=>"Stoneking", "scopus_author_id"=>"7005947824"}], "year"=>2016, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"609631256", "sgr"=>"84962343633", "issn"=>"15537404", "pmid"=>"26978189", "scopus"=>"2-s2.0-84962343633", "doi"=>"10.1371/journal.pgen.1005939", "isbn"=>"10.1101/030205"}, "id"=>"a6c44dc3-1b60-39c3-8021-d68fccb6fa0e", "abstract"=>"The mitochondrial (mt) genome is present in many copies in human cells, and intra-individual variation in mtDNA sequences is known as heteroplasmy. Recent studies found that heteroplasmies are highly tissue-specific, site-specific, and allele-specific, however the functional implications have not been explored. This study investigates variation in mtDNA copy numbers (mtCN) in 12 different tissues obtained at autopsy from 152 individuals (ranging in age from 3 days to 96 years). Three different methods to estimate mtCN were compared: shotgun sequencing (in 4 tissues), capture-enriched sequencing (in 12 tissues) and droplet digital PCR (ddPCR, in 2 tissues). The highest precision in mtCN estimation was achieved using shotgun sequencing data. However, capture-enrichment data provide reliable estimates of relative (albeit not absolute) mtCNs. Comparisons of mtCN from different tissues of the same individual revealed that mtCNs in different tissues are, with few exceptions, uncorrelated. Hence, each tissue of an individual seems to regulate mtCN in a tissue-related rather than an individual-dependent manner. Skeletal muscle (SM) samples showed an age-related decrease in mtCN that was especially pronounced in males, while there was an age-related increase in mtCN for liver (LIV) samples. MtCN in SM samples was significantly negatively correlated with both the total number of heteroplasmic sites and with minor allele frequency (MAF) at two heteroplasmic sites, 408 and 16327. Heteroplasmies at both sites are highly specific for SM, accumulate with aging and are part of functional elements that regulate mtDNA replication. These data support the hypothesis that selection acting on these heteroplasmic sites is reducing mtCN in SM of older individuals.", "link"=>"http://www.mendeley.com/research/agerelated-heteroplasmyrelated-variation-human-mtdna-copy-number", "reader_count"=>69, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>4, "Researcher"=>28, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>10, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>4, "Researcher"=>28, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>10, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Engineering"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>22, "Agricultural and Biological Sciences"=>28, "Medicine and Dentistry"=>4, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Computer Science"=>3, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>28}, "Computer Science"=>{"Computer Science"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>22}, "Unspecified"=>{"Unspecified"=>7}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Ireland"=>1, "Switzerland"=>1}, "group_count"=>3}

Scopus | Further Information

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