The disruptive positions in human G-quadruplex motifs are less polymorphic and more conserved than their neutral counterparts
Identifieur interne : 002764 ( Main/Exploration ); précédent : 002763; suivant : 002765The disruptive positions in human G-quadruplex motifs are less polymorphic and more conserved than their neutral counterparts
Auteurs : Sigve Nakken [Norvège] ; Torbj Rn Rognes [Norvège] ; Eivind Hovig [Norvège]Source :
- Nucleic Acids Research [ 0305-1048 ] ; 2009.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , analysis : Guanine.
- chemical , chemistry : DNA.
- Base Sequence, Conserved Sequence, G-Quadruplexes, Genome, Human, Humans, Polymorphism, Single Nucleotide.
Abstract
Specific guanine-rich sequence motifs in the human genome have considerable potential to form four-stranded structures known as G-quadruplexes or G4 DNA. The enrichment of these motifs in key chromosomal regions has suggested a functional role for the G-quadruplex structure in genomic regulation. In this work, we have examined the spectrum of nucleotide substitutions in G4 motifs, and related this spectrum to G4 prevalence. Data collected from the large repository of human SNPs indicates that the core feature of G-quadruplex motifs, 5′-GGG-3′, exhibits specific mutational patterns that preserve the potential for G4 formation. In particular, we find a genome-wide pattern in which sites that disrupt the guanine triplets are more conserved and less polymorphic than their neutral counterparts. This also holds when considering non-CpG sites only. However, the low level of polymorphisms in guanine tracts is not only confined to G4 motifs. A complete mapping of DNA three-mers at guanine polymorphisms indicated that short guanine tracts are the most under-represented sequence context at polymorphic sites. Furthermore, we provide evidence for a strand bias upstream of human genes. Here, a significantly lower rate of G4-disruptive SNPs on the non-template strand supports a higher relative influence of G4 formation on this strand during transcription.
Url:
DOI: 10.1093/nar/gkp590
PubMed: 19617376
PubMed Central: 2761265
Affiliations:
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conserved than their neutral counterparts</title><author><name sortKey="Nakken, Sigve" sort="Nakken, Sigve" uniqKey="Nakken S" first="Sigve" last="Nakken">Sigve Nakken</name><affiliation wicri:level="3"><nlm:aff id="AFF1">Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, NO-0027, Oslo,</nlm:aff><country>Norvège</country><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName><wicri:orgArea>Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, NO-0027</wicri:orgArea></affiliation></author><author><name sortKey="Rognes, Torbj Rn" sort="Rognes, Torbj Rn" uniqKey="Rognes T" first="Torbj Rn" last="Rognes">Torbj Rn Rognes</name><affiliation wicri:level="3"><nlm:aff id="AFF1">Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, NO-0027, Oslo,</nlm:aff><country>Norvège</country><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName><wicri:orgArea>Centre for Molecular Biology and Neuroscience, Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, NO-0027</wicri:orgArea></affiliation><affiliation wicri:level="3"><nlm:aff id="AFF1">Department of Informatics, University of Oslo, PO Box 1080 Blindern, NO-0316, Oslo,</nlm:aff><country>Norvège</country><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName><wicri:orgArea>Department of Informatics, University of Oslo, PO Box 1080 Blindern, NO-0316</wicri:orgArea></affiliation></author><author><name sortKey="Hovig, Eivind" sort="Hovig, Eivind" uniqKey="Hovig E" first="Eivind" last="Hovig">Eivind Hovig</name><affiliation wicri:level="3"><nlm:aff id="AFF1">Department of Informatics, University of Oslo, PO Box 1080 Blindern, NO-0316, Oslo,</nlm:aff><country>Norvège</country><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName><wicri:orgArea>Department of Informatics, University of Oslo, PO Box 1080 Blindern, NO-0316</wicri:orgArea></affiliation><affiliation><nlm:aff wicri:cut=" and" id="AFF1">Department of Tumor Biology, Institute for Cancer Research</nlm:aff><wicri:noCountry code="subfield">Institute for Cancer Research</wicri:noCountry></affiliation><affiliation wicri:level="3"><nlm:aff id="AFF1">Department of Medical Informatics, Oslo University Hospital, Norwegian Radium Hospital, Montebello, NO-0310, Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Department of Medical Informatics, Oslo University Hospital, Norwegian Radium Hospital, Montebello, NO-0310, Oslo</wicri:regionArea><placeName><settlement type="city">Oslo</settlement><region nuts="2">Østlandet</region></placeName></affiliation></author></analytic><series><title level="j">Nucleic Acids Research</title><idno type="ISSN">0305-1048</idno><idno type="eISSN">1362-4962</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Base Sequence</term><term>Conserved Sequence</term><term>DNA (chemistry)</term><term>G-Quadruplexes</term><term>Genome, Human</term><term>Guanine (analysis)</term><term>Humans</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN ()</term><term>G-quadruplexes</term><term>Guanine (analyse)</term><term>Génome humain</term><term>Humains</term><term>Polymorphisme de nucléotide simple</term><term>Séquence conservée</term><term>Séquence nucléotidique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Guanine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>DNA</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Guanine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Base Sequence</term><term>Conserved Sequence</term><term>G-Quadruplexes</term><term>Genome, Human</term><term>Humans</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ADN</term><term>G-quadruplexes</term><term>Génome humain</term><term>Humains</term><term>Polymorphisme de nucléotide simple</term><term>Séquence conservée</term><term>Séquence nucléotidique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Specific guanine-rich sequence motifs in the human genome have considerable potential to form four-stranded structures known as G-quadruplexes or G4 DNA. The enrichment of these motifs in key chromosomal regions has suggested a functional role for the G-quadruplex structure in genomic regulation. In this work, we have examined the spectrum of nucleotide substitutions in G4 motifs, and related this spectrum to G4 prevalence. Data collected from the large repository of human SNPs indicates that the core feature of G-quadruplex motifs, 5′-GGG-3′, exhibits specific mutational patterns that preserve the potential for G4 formation. In particular, we find a genome-wide pattern in which sites that disrupt the guanine triplets are more conserved and less polymorphic than their neutral counterparts. This also holds when considering non-CpG sites only. However, the low level of polymorphisms in guanine tracts is not only confined to G4 motifs. A complete mapping of DNA three-mers at guanine polymorphisms indicated that short guanine tracts are the most under-represented sequence context at polymorphic sites. Furthermore, we provide evidence for a strand bias upstream of human genes. Here, a significantly lower rate of G4-disruptive SNPs on the non-template strand supports a higher relative influence of G4 formation on this strand during transcription.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Sen, D" uniqKey="Sen D">D Sen</name></author><author><name sortKey="Gilbert, W" uniqKey="Gilbert W">W Gilbert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gellert, M" uniqKey="Gellert M">M Gellert</name></author><author><name sortKey="Lipsett, Mn" uniqKey="Lipsett M">MN Lipsett</name></author><author><name sortKey="Davies, Dr" uniqKey="Davies D">DR Davies</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hazel, P" uniqKey="Hazel P">P Hazel</name></author><author><name sortKey="Huppert, J" uniqKey="Huppert J">J Huppert</name></author><author><name sortKey="Balasubramanian, S" uniqKey="Balasubramanian S">S 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Burgers</name></author><author><name sortKey="Kunkel, Ta" uniqKey="Kunkel T">TA Kunkel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kresnak, Mt" uniqKey="Kresnak M">MT Kresnak</name></author><author><name sortKey="Davidson, Rl" uniqKey="Davidson R">RL Davidson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Platzer, M" uniqKey="Platzer M">M Platzer</name></author><author><name sortKey="Hiller, M" uniqKey="Hiller M">M Hiller</name></author><author><name sortKey="Szafranski, K" uniqKey="Szafranski K">K Szafranski</name></author><author><name sortKey="Jahn, N" uniqKey="Jahn N">N Jahn</name></author><author><name sortKey="Hampe, J" uniqKey="Hampe J">J Hampe</name></author><author><name sortKey="Schreiber, S" uniqKey="Schreiber S">S Schreiber</name></author><author><name sortKey="Backofen, R" uniqKey="Backofen R">R Backofen</name></author><author><name sortKey="Huse, K" uniqKey="Huse K">K Huse</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Siva, N" uniqKey="Siva N">N Siva</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Norvège</li></country><region><li>Østlandet</li></region><settlement><li>Oslo</li></settlement></list><tree><country name="Norvège"><region name="Østlandet"><name sortKey="Nakken, Sigve" sort="Nakken, Sigve" uniqKey="Nakken S" first="Sigve" last="Nakken">Sigve Nakken</name></region><name sortKey="Hovig, Eivind" sort="Hovig, Eivind" uniqKey="Hovig E" first="Eivind" last="Hovig">Eivind Hovig</name><name sortKey="Hovig, Eivind" sort="Hovig, Eivind" uniqKey="Hovig E" first="Eivind" last="Hovig">Eivind Hovig</name><name sortKey="Rognes, Torbj Rn" sort="Rognes, Torbj Rn" uniqKey="Rognes T" first="Torbj Rn" last="Rognes">Torbj Rn Rognes</name><name sortKey="Rognes, Torbj Rn" sort="Rognes, Torbj Rn" uniqKey="Rognes T" first="Torbj Rn" last="Rognes">Torbj Rn 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