Deep sequencing of the mitochondrial genome reveals common heteroplasmic sites in NADH dehydrogenase genes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-02-08

AUTHORS

Chunyu Liu, Jessica L. Fetterman, Poching Liu, Yan Luo, Martin G. Larson, Ramachandran S. Vasan, Jun Zhu, Daniel Levy

ABSTRACT

Increasing evidence implicates mitochondrial dysfunction in aging and age-related conditions. But little is known about the molecular basis for this connection. A possible cause may be mutations in the mitochondrial DNA (mtDNA), which are often heteroplasmic—the joint presence of different alleles at a single locus in the same individual. However, the involvement of mtDNA heteroplasmy in aging and age-related conditions has not been investigated thoroughly. We deep-sequenced the complete mtDNA genomes of 356 Framingham Heart Study participants (52% women, mean age 43, mean coverage 4570-fold), identified 2880 unique mutations and comprehensively annotated them by MITOMAP and PolyPhen-2. We discovered 11 heteroplasmic “hot” spots [NADH dehydrogenase (ND) subunit 1, 4, 5 and 6 genes, n = 7; cytochrome c oxidase I (COI), n = 2; 16S rRNA, n = 1; D-loop, n = 1] for which the alternative-to-reference allele ratios significantly increased with advancing age (Bonferroni correction p < 0.001). Four of these heteroplasmic mutations in ND and COI genes were predicted to be deleterious nonsynonymous mutations which may have direct impact on ATP production. We confirmed previous findings that healthy individuals carry many low-frequency heteroplasmy mutations with potentially deleterious effects. We hypothesize that the effect of a single deleterious heteroplasmy may be minimal due to a low mutant-to-wildtype allele ratio, whereas the aggregate effects of many deleterious mutations may cause changes in mitochondrial function and contribute to age-related diseases. The identification of age-related mtDNA mutations is an important step to understand the genetic architecture of age-related diseases and may uncover novel therapeutic targets for such diseases. More... »

PAGES

203-213

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00439-018-1873-4

DOI

http://dx.doi.org/10.1007/s00439-018-1873-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100915518

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29423652


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Genetics", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adult", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Alleles", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA, Mitochondrial", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Genome, Mitochondrial", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "High-Throughput Nucleotide Sequencing", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mitochondria", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mutation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "NADH Dehydrogenase", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "RNA, Ribosomal, 16S", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Department of Biostatistics, Boston University, Boston, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.189504.1", 
          "name": [
            "Population Sciences Branch, NHLBI/NHI, Bethesda, MD, USA", 
            "Framingham Heart Study, Framingham, MA, USA", 
            "Department of Biostatistics, Boston University, Boston, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Liu", 
        "givenName": "Chunyu", 
        "id": "sg:person.01247473740.62", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01247473740.62"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "School of Medicine, Boston University, Boston, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.189504.1", 
          "name": [
            "School of Medicine, Boston University, Boston, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Fetterman", 
        "givenName": "Jessica L.", 
        "id": "sg:person.01261765152.51", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01261765152.51"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "DNA Sequencing and Genomics Core, NHLBI/NIH, Bethesda, MD, USA", 
          "id": "http://www.grid.ac/institutes/grid.279885.9", 
          "name": [
            "DNA Sequencing and Genomics Core, NHLBI/NIH, Bethesda, MD, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Liu", 
        "givenName": "Poching", 
        "id": "sg:person.01245347217.82", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01245347217.82"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "DNA Sequencing and Genomics Core, NHLBI/NIH, Bethesda, MD, USA", 
          "id": "http://www.grid.ac/institutes/grid.279885.9", 
          "name": [
            "DNA Sequencing and Genomics Core, NHLBI/NIH, Bethesda, MD, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Luo", 
        "givenName": "Yan", 
        "id": "sg:person.01216535042.29", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01216535042.29"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biostatistics, Boston University, Boston, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.189504.1", 
          "name": [
            "Framingham Heart Study, Framingham, MA, USA", 
            "Department of Biostatistics, Boston University, Boston, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Larson", 
        "givenName": "Martin G.", 
        "id": "sg:person.010274452357.12", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010274452357.12"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "School of Medicine, Boston University, Boston, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.189504.1", 
          "name": [
            "Framingham Heart Study, Framingham, MA, USA", 
            "School of Medicine, Boston University, Boston, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Vasan", 
        "givenName": "Ramachandran S.", 
        "id": "sg:person.01313052166.05", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313052166.05"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "System Biology Center, NHLBI/NHI, Bethesda, MD, USA", 
          "id": "http://www.grid.ac/institutes/grid.279885.9", 
          "name": [
            "System Biology Center, NHLBI/NHI, Bethesda, MD, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zhu", 
        "givenName": "Jun", 
        "id": "sg:person.014660221440.61", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014660221440.61"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Framingham Heart Study, Framingham, MA, USA", 
          "id": "http://www.grid.ac/institutes/grid.510954.c", 
          "name": [
            "Population Sciences Branch, NHLBI/NHI, Bethesda, MD, USA", 
            "Framingham Heart Study, Framingham, MA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Levy", 
        "givenName": "Daniel", 
        "id": "sg:person.01302706715.35", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01302706715.35"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/nrg1606", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024549229", 
          "https://doi.org/10.1038/nrg1606"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08802", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017257177", 
          "https://doi.org/10.1038/nature08802"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrg3966", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018152264", 
          "https://doi.org/10.1038/nrg3966"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng1451", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008794782", 
          "https://doi.org/10.1038/ng1451"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/13779", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040703029", 
          "https://doi.org/10.1038/13779"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2164-12-464", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006522601", 
          "https://doi.org/10.1186/1471-2164-12-464"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00125-009-1510-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032675583", 
          "https://doi.org/10.1007/s00125-009-1510-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature02517", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049627873", 
          "https://doi.org/10.1038/nature02517"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s12862-015-0312-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013568149", 
          "https://doi.org/10.1186/s12862-015-0312-6"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/srep12049", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005834763", 
          "https://doi.org/10.1038/srep12049"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-02-08", 
    "datePublishedReg": "2018-02-08", 
    "description": "Increasing evidence implicates mitochondrial dysfunction in aging and age-related conditions. But little is known about the molecular basis for this connection. A possible cause may be mutations in the mitochondrial DNA (mtDNA), which are often heteroplasmic\u2014the joint presence of different alleles at a single locus in the same individual. However, the involvement of mtDNA heteroplasmy in aging and age-related conditions has not been investigated thoroughly. We deep-sequenced the complete mtDNA genomes of 356 Framingham Heart Study participants (52% women, mean age 43, mean coverage 4570-fold), identified 2880 unique mutations and comprehensively annotated them by MITOMAP and PolyPhen-2. We discovered 11 heteroplasmic \u201chot\u201d spots [NADH dehydrogenase (ND) subunit 1, 4, 5 and 6 genes, n\u00a0=\u00a07; cytochrome c oxidase I (COI), n\u00a0=\u00a02; 16S rRNA, n\u00a0=\u00a01; D-loop, n\u00a0=\u00a01] for which the alternative-to-reference allele ratios significantly increased with advancing age (Bonferroni correction p\u00a0<\u00a00.001). Four of these heteroplasmic mutations in ND and COI genes were predicted to be deleterious nonsynonymous mutations which may have direct impact on ATP production. We confirmed previous findings that healthy individuals carry many low-frequency heteroplasmy mutations with potentially deleterious effects. We hypothesize that the effect of a single deleterious heteroplasmy may be minimal due to a low mutant-to-wildtype allele ratio, whereas the aggregate effects of many deleterious mutations may cause changes in mitochondrial function and contribute to age-related diseases. The identification of age-related mtDNA mutations is an important step to understand the genetic architecture of age-related diseases and may uncover novel therapeutic targets for such diseases.", 
    "genre": "article", 
    "id": "sg:pub.10.1007/s00439-018-1873-4", 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2720189", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.7170274", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2725872", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1085982", 
        "issn": [
          "0340-6717", 
          "1432-1203"
        ], 
        "name": "Human Genetics", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "3", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "137"
      }
    ], 
    "keywords": [
      "age-related conditions", 
      "age-related diseases", 
      "Framingham Heart Study participants", 
      "novel therapeutic target", 
      "age-related mtDNA mutations", 
      "healthy individuals", 
      "therapeutic target", 
      "NADH dehydrogenase genes", 
      "complete mtDNA genomes", 
      "deleterious nonsynonymous mutations", 
      "study participants", 
      "mitochondrial dysfunction", 
      "such diseases", 
      "disease", 
      "allele ratios", 
      "mitochondrial genome", 
      "COI gene", 
      "deleterious heteroplasmies", 
      "mitochondrial function", 
      "genetic architecture", 
      "mtDNA genome", 
      "mitochondrial DNA", 
      "deleterious effects", 
      "dehydrogenase gene", 
      "deleterious mutations", 
      "heteroplasmic sites", 
      "single locus", 
      "mtDNA heteroplasmy", 
      "unique mutations", 
      "molecular basis", 
      "heteroplasmic mutations", 
      "deep sequencing", 
      "mtDNA mutations", 
      "ATP production", 
      "PolyPhen-2", 
      "nonsynonymous mutations", 
      "different alleles", 
      "same individual", 
      "possible causes", 
      "mutations", 
      "previous findings", 
      "genome", 
      "heteroplasmy", 
      "genes", 
      "dysfunction", 
      "individuals", 
      "age", 
      "aging", 
      "effect", 
      "cause", 
      "involvement", 
      "mutants", 
      "participants", 
      "MITOMAP", 
      "loci", 
      "sequencing", 
      "DNA", 
      "findings", 
      "alleles", 
      "evidence", 
      "target", 
      "important step", 
      "joint presence", 
      "ratio", 
      "presence", 
      "changes", 
      "identification", 
      "sites", 
      "function", 
      "production", 
      "conditions", 
      "direct impact", 
      "alternative", 
      "impact", 
      "spots", 
      "basis", 
      "aggregate effect", 
      "step", 
      "connection", 
      "architecture", 
      "Nd"
    ], 
    "name": "Deep sequencing of the mitochondrial genome reveals common heteroplasmic sites in NADH dehydrogenase genes", 
    "pagination": "203-213", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1100915518"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s00439-018-1873-4"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29423652"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s00439-018-1873-4", 
      "https://app.dimensions.ai/details/publication/pub.1100915518"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-12-01T06:37", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20221201/entities/gbq_results/article/article_770.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1007/s00439-018-1873-4"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00439-018-1873-4'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00439-018-1873-4'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00439-018-1873-4'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00439-018-1873-4'


 

This table displays all metadata directly associated to this object as RDF triples.

298 TRIPLES      21 PREDICATES      128 URIs      110 LITERALS      19 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s00439-018-1873-4 schema:about N00898336b9e343ce88c65d47d9a0ad75
2 N17202bb8068e425b820c453c04e55229
3 N1fb552aa899e4354b6859be9d02089dd
4 N4c567e4b05664e8f86f913f95ef72d57
5 N65fcff2da41645fb96a4fac373e882c4
6 N899e290db5c7408181eeda3aa9c1279d
7 Na44d70f94270440d92997e66e215b873
8 Nb80fbc3e11754c89aaf70f6125e470f7
9 Nbf1bd837e87f49dc83d014f7d2ba166d
10 Nc222d32431834251a881f2cc7391be7c
11 Nd2cda85278334da4907a58f9ab15a48d
12 Neba86c045c5b4494996fca83609d2fc7
13 anzsrc-for:06
14 anzsrc-for:0604
15 schema:author Na38244cd5cb24b7e8f6b63c3a2693042
16 schema:citation sg:pub.10.1007/s00125-009-1510-9
17 sg:pub.10.1038/13779
18 sg:pub.10.1038/nature02517
19 sg:pub.10.1038/nature08802
20 sg:pub.10.1038/ng1451
21 sg:pub.10.1038/nrg1606
22 sg:pub.10.1038/nrg3966
23 sg:pub.10.1038/srep12049
24 sg:pub.10.1186/1471-2164-12-464
25 sg:pub.10.1186/s12862-015-0312-6
26 schema:datePublished 2018-02-08
27 schema:datePublishedReg 2018-02-08
28 schema:description Increasing evidence implicates mitochondrial dysfunction in aging and age-related conditions. But little is known about the molecular basis for this connection. A possible cause may be mutations in the mitochondrial DNA (mtDNA), which are often heteroplasmic—the joint presence of different alleles at a single locus in the same individual. However, the involvement of mtDNA heteroplasmy in aging and age-related conditions has not been investigated thoroughly. We deep-sequenced the complete mtDNA genomes of 356 Framingham Heart Study participants (52% women, mean age 43, mean coverage 4570-fold), identified 2880 unique mutations and comprehensively annotated them by MITOMAP and PolyPhen-2. We discovered 11 heteroplasmic “hot” spots [NADH dehydrogenase (ND) subunit 1, 4, 5 and 6 genes, n = 7; cytochrome c oxidase I (COI), n = 2; 16S rRNA, n = 1; D-loop, n = 1] for which the alternative-to-reference allele ratios significantly increased with advancing age (Bonferroni correction p < 0.001). Four of these heteroplasmic mutations in ND and COI genes were predicted to be deleterious nonsynonymous mutations which may have direct impact on ATP production. We confirmed previous findings that healthy individuals carry many low-frequency heteroplasmy mutations with potentially deleterious effects. We hypothesize that the effect of a single deleterious heteroplasmy may be minimal due to a low mutant-to-wildtype allele ratio, whereas the aggregate effects of many deleterious mutations may cause changes in mitochondrial function and contribute to age-related diseases. The identification of age-related mtDNA mutations is an important step to understand the genetic architecture of age-related diseases and may uncover novel therapeutic targets for such diseases.
29 schema:genre article
30 schema:isAccessibleForFree true
31 schema:isPartOf N2a2971e4c4dc4c4897ffc965be2f1fcc
32 N3e0695e1265644f39798ad9938636695
33 sg:journal.1085982
34 schema:keywords ATP production
35 COI gene
36 DNA
37 Framingham Heart Study participants
38 MITOMAP
39 NADH dehydrogenase genes
40 Nd
41 PolyPhen-2
42 age
43 age-related conditions
44 age-related diseases
45 age-related mtDNA mutations
46 aggregate effect
47 aging
48 allele ratios
49 alleles
50 alternative
51 architecture
52 basis
53 cause
54 changes
55 complete mtDNA genomes
56 conditions
57 connection
58 deep sequencing
59 dehydrogenase gene
60 deleterious effects
61 deleterious heteroplasmies
62 deleterious mutations
63 deleterious nonsynonymous mutations
64 different alleles
65 direct impact
66 disease
67 dysfunction
68 effect
69 evidence
70 findings
71 function
72 genes
73 genetic architecture
74 genome
75 healthy individuals
76 heteroplasmic mutations
77 heteroplasmic sites
78 heteroplasmy
79 identification
80 impact
81 important step
82 individuals
83 involvement
84 joint presence
85 loci
86 mitochondrial DNA
87 mitochondrial dysfunction
88 mitochondrial function
89 mitochondrial genome
90 molecular basis
91 mtDNA genome
92 mtDNA heteroplasmy
93 mtDNA mutations
94 mutants
95 mutations
96 nonsynonymous mutations
97 novel therapeutic target
98 participants
99 possible causes
100 presence
101 previous findings
102 production
103 ratio
104 same individual
105 sequencing
106 single locus
107 sites
108 spots
109 step
110 study participants
111 such diseases
112 target
113 therapeutic target
114 unique mutations
115 schema:name Deep sequencing of the mitochondrial genome reveals common heteroplasmic sites in NADH dehydrogenase genes
116 schema:pagination 203-213
117 schema:productId N3d9084b0dcc04df99ef95e8b3c0e44ac
118 N681c513d19184ca099087bdba7b3dd72
119 Nda14f7968cef457b8051651a764f442b
120 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100915518
121 https://doi.org/10.1007/s00439-018-1873-4
122 schema:sdDatePublished 2022-12-01T06:37
123 schema:sdLicense https://scigraph.springernature.com/explorer/license/
124 schema:sdPublisher N0c0297c23d2c4bd6889e956c99c2c9ad
125 schema:url https://doi.org/10.1007/s00439-018-1873-4
126 sgo:license sg:explorer/license/
127 sgo:sdDataset articles
128 rdf:type schema:ScholarlyArticle
129 N00898336b9e343ce88c65d47d9a0ad75 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
130 schema:name Mutation
131 rdf:type schema:DefinedTerm
132 N078793bc194847cd81dab985c650d391 rdf:first sg:person.014660221440.61
133 rdf:rest Ne201f9c6c3e940878409d40b580e0294
134 N0c0297c23d2c4bd6889e956c99c2c9ad schema:name Springer Nature - SN SciGraph project
135 rdf:type schema:Organization
136 N17202bb8068e425b820c453c04e55229 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
137 schema:name Genome, Mitochondrial
138 rdf:type schema:DefinedTerm
139 N1fb552aa899e4354b6859be9d02089dd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
140 schema:name Humans
141 rdf:type schema:DefinedTerm
142 N2a2971e4c4dc4c4897ffc965be2f1fcc schema:volumeNumber 137
143 rdf:type schema:PublicationVolume
144 N3d9084b0dcc04df99ef95e8b3c0e44ac schema:name dimensions_id
145 schema:value pub.1100915518
146 rdf:type schema:PropertyValue
147 N3e0695e1265644f39798ad9938636695 schema:issueNumber 3
148 rdf:type schema:PublicationIssue
149 N4c567e4b05664e8f86f913f95ef72d57 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
150 schema:name Alleles
151 rdf:type schema:DefinedTerm
152 N65fcff2da41645fb96a4fac373e882c4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
153 schema:name Mitochondria
154 rdf:type schema:DefinedTerm
155 N681c513d19184ca099087bdba7b3dd72 schema:name pubmed_id
156 schema:value 29423652
157 rdf:type schema:PropertyValue
158 N899e290db5c7408181eeda3aa9c1279d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
159 schema:name RNA, Ribosomal, 16S
160 rdf:type schema:DefinedTerm
161 Na38244cd5cb24b7e8f6b63c3a2693042 rdf:first sg:person.01247473740.62
162 rdf:rest Ne9a719678f5a42efb82b9f9b4ae69ce9
163 Na44d70f94270440d92997e66e215b873 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
164 schema:name Adult
165 rdf:type schema:DefinedTerm
166 Nb80fbc3e11754c89aaf70f6125e470f7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
167 schema:name High-Throughput Nucleotide Sequencing
168 rdf:type schema:DefinedTerm
169 Nbcdfba27013e4fcb810d80369c8fb83a rdf:first sg:person.01216535042.29
170 rdf:rest Nbd2a0dc6454441fe97851892cffe8377
171 Nbd2a0dc6454441fe97851892cffe8377 rdf:first sg:person.010274452357.12
172 rdf:rest Ncb0274f2707f4d099e317da5c40b55e2
173 Nbf1bd837e87f49dc83d014f7d2ba166d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
174 schema:name Male
175 rdf:type schema:DefinedTerm
176 Nc222d32431834251a881f2cc7391be7c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
177 schema:name Female
178 rdf:type schema:DefinedTerm
179 Ncb0274f2707f4d099e317da5c40b55e2 rdf:first sg:person.01313052166.05
180 rdf:rest N078793bc194847cd81dab985c650d391
181 Nd2cda85278334da4907a58f9ab15a48d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
182 schema:name NADH Dehydrogenase
183 rdf:type schema:DefinedTerm
184 Nda14f7968cef457b8051651a764f442b schema:name doi
185 schema:value 10.1007/s00439-018-1873-4
186 rdf:type schema:PropertyValue
187 Ne201f9c6c3e940878409d40b580e0294 rdf:first sg:person.01302706715.35
188 rdf:rest rdf:nil
189 Ne9a719678f5a42efb82b9f9b4ae69ce9 rdf:first sg:person.01261765152.51
190 rdf:rest Nf98fce9853ee452bb8fdc993eab42d42
191 Neba86c045c5b4494996fca83609d2fc7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
192 schema:name DNA, Mitochondrial
193 rdf:type schema:DefinedTerm
194 Nf98fce9853ee452bb8fdc993eab42d42 rdf:first sg:person.01245347217.82
195 rdf:rest Nbcdfba27013e4fcb810d80369c8fb83a
196 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
197 schema:name Biological Sciences
198 rdf:type schema:DefinedTerm
199 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
200 schema:name Genetics
201 rdf:type schema:DefinedTerm
202 sg:grant.2720189 http://pending.schema.org/fundedItem sg:pub.10.1007/s00439-018-1873-4
203 rdf:type schema:MonetaryGrant
204 sg:grant.2725872 http://pending.schema.org/fundedItem sg:pub.10.1007/s00439-018-1873-4
205 rdf:type schema:MonetaryGrant
206 sg:grant.7170274 http://pending.schema.org/fundedItem sg:pub.10.1007/s00439-018-1873-4
207 rdf:type schema:MonetaryGrant
208 sg:journal.1085982 schema:issn 0340-6717
209 1432-1203
210 schema:name Human Genetics
211 schema:publisher Springer Nature
212 rdf:type schema:Periodical
213 sg:person.010274452357.12 schema:affiliation grid-institutes:grid.189504.1
214 schema:familyName Larson
215 schema:givenName Martin G.
216 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010274452357.12
217 rdf:type schema:Person
218 sg:person.01216535042.29 schema:affiliation grid-institutes:grid.279885.9
219 schema:familyName Luo
220 schema:givenName Yan
221 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01216535042.29
222 rdf:type schema:Person
223 sg:person.01245347217.82 schema:affiliation grid-institutes:grid.279885.9
224 schema:familyName Liu
225 schema:givenName Poching
226 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01245347217.82
227 rdf:type schema:Person
228 sg:person.01247473740.62 schema:affiliation grid-institutes:grid.189504.1
229 schema:familyName Liu
230 schema:givenName Chunyu
231 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01247473740.62
232 rdf:type schema:Person
233 sg:person.01261765152.51 schema:affiliation grid-institutes:grid.189504.1
234 schema:familyName Fetterman
235 schema:givenName Jessica L.
236 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01261765152.51
237 rdf:type schema:Person
238 sg:person.01302706715.35 schema:affiliation grid-institutes:grid.510954.c
239 schema:familyName Levy
240 schema:givenName Daniel
241 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01302706715.35
242 rdf:type schema:Person
243 sg:person.01313052166.05 schema:affiliation grid-institutes:grid.189504.1
244 schema:familyName Vasan
245 schema:givenName Ramachandran S.
246 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313052166.05
247 rdf:type schema:Person
248 sg:person.014660221440.61 schema:affiliation grid-institutes:grid.279885.9
249 schema:familyName Zhu
250 schema:givenName Jun
251 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014660221440.61
252 rdf:type schema:Person
253 sg:pub.10.1007/s00125-009-1510-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032675583
254 https://doi.org/10.1007/s00125-009-1510-9
255 rdf:type schema:CreativeWork
256 sg:pub.10.1038/13779 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040703029
257 https://doi.org/10.1038/13779
258 rdf:type schema:CreativeWork
259 sg:pub.10.1038/nature02517 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049627873
260 https://doi.org/10.1038/nature02517
261 rdf:type schema:CreativeWork
262 sg:pub.10.1038/nature08802 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017257177
263 https://doi.org/10.1038/nature08802
264 rdf:type schema:CreativeWork
265 sg:pub.10.1038/ng1451 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008794782
266 https://doi.org/10.1038/ng1451
267 rdf:type schema:CreativeWork
268 sg:pub.10.1038/nrg1606 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024549229
269 https://doi.org/10.1038/nrg1606
270 rdf:type schema:CreativeWork
271 sg:pub.10.1038/nrg3966 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018152264
272 https://doi.org/10.1038/nrg3966
273 rdf:type schema:CreativeWork
274 sg:pub.10.1038/srep12049 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005834763
275 https://doi.org/10.1038/srep12049
276 rdf:type schema:CreativeWork
277 sg:pub.10.1186/1471-2164-12-464 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006522601
278 https://doi.org/10.1186/1471-2164-12-464
279 rdf:type schema:CreativeWork
280 sg:pub.10.1186/s12862-015-0312-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013568149
281 https://doi.org/10.1186/s12862-015-0312-6
282 rdf:type schema:CreativeWork
283 grid-institutes:grid.189504.1 schema:alternateName Department of Biostatistics, Boston University, Boston, MA, USA
284 School of Medicine, Boston University, Boston, MA, USA
285 schema:name Department of Biostatistics, Boston University, Boston, MA, USA
286 Framingham Heart Study, Framingham, MA, USA
287 Population Sciences Branch, NHLBI/NHI, Bethesda, MD, USA
288 School of Medicine, Boston University, Boston, MA, USA
289 rdf:type schema:Organization
290 grid-institutes:grid.279885.9 schema:alternateName DNA Sequencing and Genomics Core, NHLBI/NIH, Bethesda, MD, USA
291 System Biology Center, NHLBI/NHI, Bethesda, MD, USA
292 schema:name DNA Sequencing and Genomics Core, NHLBI/NIH, Bethesda, MD, USA
293 System Biology Center, NHLBI/NHI, Bethesda, MD, USA
294 rdf:type schema:Organization
295 grid-institutes:grid.510954.c schema:alternateName Framingham Heart Study, Framingham, MA, USA
296 schema:name Framingham Heart Study, Framingham, MA, USA
297 Population Sciences Branch, NHLBI/NHI, Bethesda, MD, USA
298 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...