Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans
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{"title"=>"Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans", "type"=>"journal", "authors"=>[{"first_name"=>"Angela", "last_name"=>"Pyle", "scopus_author_id"=>"15740165200"}, {"first_name"=>"Gavin", "last_name"=>"Hudson", "scopus_author_id"=>"16230214700"}, {"first_name"=>"Ian J.", "last_name"=>"Wilson", "scopus_author_id"=>"22999257500"}, {"first_name"=>"Jonathan", "last_name"=>"Coxhead", "scopus_author_id"=>"6507972484"}, {"first_name"=>"Tania", "last_name"=>"Smertenko", "scopus_author_id"=>"55951260700"}, {"first_name"=>"Mary", "last_name"=>"Herbert", "scopus_author_id"=>"7103313424"}, {"first_name"=>"Mauro", "last_name"=>"Santibanez-Koref", "scopus_author_id"=>"7004717757"}, {"first_name"=>"Patrick F.", "last_name"=>"Chinnery", "scopus_author_id"=>"9533655500"}], "year"=>2015, "source"=>"PLoS Genetics", "identifiers"=>{"isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pmid"=>"25973765", "doi"=>"10.1371/journal.pgen.1005040", "pui"=>"604818034", "issn"=>"15537404", "sgr"=>"84930801786", "scopus"=>"2-s2.0-84930801786"}, "id"=>"9e2c40ea-2bae-316a-88a8-eba7c276395c", "abstract"=>"Recent reports have questioned the accepted dogma that mammalian mitochondrial DNA (mtDNA) is strictly maternally inherited. In humans, the argument hinges on detecting a signature of inter-molecular recombination in mtDNA sequences sampled at the population level, inferring a paternal source for the mixed haplotypes. However, interpreting these data is fraught with difficulty, and direct experimental evidence is lacking. Using extreme-high depth mtDNA re-sequencing up to ~1.2 million-fold coverage, we find no evidence that paternal mtDNA haplotypes are transmitted to offspring in humans, thus excluding a simple dilution mechanism for uniparental transmission of mtDNA present in all healthy individuals. Our findings indicate that an active mechanism eliminates paternal mtDNA which likely acts at the molecular level.", "link"=>"http://www.mendeley.com/research/extremedepth-resequencing-mitochondrial-dna-finds-evidence-paternal-transmission-humans", "reader_count"=>39, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>9, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>3, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>9, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>3, "Student > Master"=>6, "Other"=>2, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>24, "Medicine and Dentistry"=>4, "Neuroscience"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>24}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Switzerland"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2068510"], "description"=>"<p>(a) Position of the discordant haplotypes on the mitochondrial genome. Thick horizontal bars show the position of the PCR amplicons. (b) Average sequencing depth +/- 95% confidence intervals for the two amplicons in all four trios. (c) Population variant allele frequencies for the two amplicons, indicating position of motif variants.</p>", "links"=>[], "tags"=>["mitochondrial DNA", "mtDNA haplotypes", "argument hinges", "population level", "uniparental transmission", "dilution mechanism", "Paternal Transmission", "mtDNA sequences"], "article_id"=>1415392, "categories"=>["Biological Sciences"], "users"=>["Angela Pyle", "Gavin Hudson", "Ian J. Wilson", "Jonathan Coxhead", "Tania Smertenko", "Mary Herbert", "Mauro Santibanez-Koref", "Patrick F. Chinnery"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005040.g001", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Extreme_deep_sequencing_in_trios_with_discordant_paternal_and_maternal_mitochondrial_DNA_/1415392", "title"=>"Extreme deep sequencing in trios with discordant paternal and maternal mitochondrial DNA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-14 03:39:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/2068511"], "description"=>"<p>Calculations are based on the comparison of two Poisson distributions as described by Skellam [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005040#pgen.1005040.ref025\" target=\"_blank\">25</a>], assuming the same mtDNA fold coverage in mothers and offspring (see text for a full description of the <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005040#sec004\" target=\"_blank\">methods</a>). Each graph shows the power to detect a paternal contribution to the mtDNA in the offspring of the trios studied here based for different degrees of ultra-deep sequencing coverage, and for different background levels of mtDNA heteroplasmy seen in the mothers, which in this study were 4.3 x 10<sup>–5</sup>, 6.0 x 10<sup>–5</sup>, 5.7 x 10<sup>–5</sup>, and 7.6 x 10<sup>–5</sup>.</p>", "links"=>[], "tags"=>["mitochondrial DNA", "mtDNA haplotypes", "argument hinges", "population level", "uniparental transmission", "dilution mechanism", "Paternal Transmission", "mtDNA sequences"], "article_id"=>1415393, "categories"=>["Biological Sciences"], "users"=>["Angela Pyle", "Gavin Hudson", "Ian J. Wilson", "Jonathan Coxhead", "Tania Smertenko", "Mary Herbert", "Mauro Santibanez-Koref", "Patrick F. Chinnery"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005040.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Power_to_detect_paternally_transmitted_mtDNA_in_the_children_studied_here_based_on_the_observed_ultra_deep_mtDNA_sequence_data_/1415393", "title"=>"Power to detect paternally transmitted mtDNA in the children studied here based on the observed ultra-deep mtDNA sequence data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-14 03:39:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/2068512"], "description"=>"<p>Two or three-allele mtDNA motifs define the discordant haplotypes also shown in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005040#pgen.1005040.g001\" target=\"_blank\">Fig 1A</a>. Raw reads from extreme high-depth mtDNA sequencing across all four motifs to detect paternal haplotypes. The number of possible paternal ‘reads’ in the children was the same as the mothers from the same trio, in keeping with background noise.</p><p>Frequency of rare haplotypes in trios with discordant paternal and maternal mitochondrial DNA.</p>", "links"=>[], "tags"=>["mitochondrial DNA", "mtDNA haplotypes", "argument hinges", "population level", "uniparental transmission", "dilution mechanism", "Paternal Transmission", "mtDNA sequences"], "article_id"=>1415394, "categories"=>["Biological Sciences"], "users"=>["Angela Pyle", "Gavin Hudson", "Ian J. Wilson", "Jonathan Coxhead", "Tania Smertenko", "Mary Herbert", "Mauro Santibanez-Koref", "Patrick F. Chinnery"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005040.t001", "stats"=>{"downloads"=>3, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Frequency_of_rare_haplotypes_in_trios_with_discordant_paternal_and_maternal_mitochondrial_DNA_/1415394", "title"=>"Frequency of rare haplotypes in trios with discordant paternal and maternal mitochondrial DNA.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-14 03:39:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/2068513", "https://ndownloader.figshare.com/files/2068514", "https://ndownloader.figshare.com/files/2068515"], "description"=>"<div><p>Recent reports have questioned the accepted dogma that mammalian mitochondrial DNA (mtDNA) is strictly maternally inherited. In humans, the argument hinges on detecting a signature of inter-molecular recombination in mtDNA sequences sampled at the population level, inferring a paternal source for the mixed haplotypes. However, interpreting these data is fraught with difficulty, and direct experimental evidence is lacking. Using extreme-high depth mtDNA re-sequencing up to ~1.2 million-fold coverage, we find no evidence that paternal mtDNA haplotypes are transmitted to offspring in humans, thus excluding a simple dilution mechanism for uniparental transmission of mtDNA present in all healthy individuals. Our findings indicate that an active mechanism eliminates paternal mtDNA which likely acts at the molecular level.</p></div>", "links"=>[], "tags"=>["mitochondrial DNA", "mtDNA haplotypes", "argument hinges", "population level", "uniparental transmission", "dilution mechanism", "Paternal Transmission", "mtDNA sequences"], "article_id"=>1415395, "categories"=>["Biological Sciences"], "users"=>["Angela Pyle", "Gavin Hudson", "Ian J. Wilson", "Jonathan Coxhead", "Tania Smertenko", "Mary Herbert", "Mauro Santibanez-Koref", "Patrick F. Chinnery"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005040.s001", "https://dx.doi.org/10.1371/journal.pgen.1005040.s002", "https://dx.doi.org/10.1371/journal.pgen.1005040.s003"], "stats"=>{"downloads"=>11, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Extreme_Depth_Re_sequencing_of_Mitochondrial_DNA_Finds_No_Evidence_of_Paternal_Transmission_in_Humans_/1415395", "title"=>"Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-05-14 03:39:16"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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