Identification of novel craniofacial regulatory domains located far upstream of SOX9 and disrupted in Pierre Robin sequence
Identifieur interne : 003935 ( Pmc/Corpus ); précédent : 003934; suivant : 003936Identification of novel craniofacial regulatory domains located far upstream of SOX9 and disrupted in Pierre Robin sequence
Auteurs : Christopher T. Gordon ; Catia Attanasio ; Shipra Bhatia ; Sabina Benko ; Morad Ansari ; Tiong Y. Tan ; Arnold Munnich ; Len A. Pennacchio ; Véronique Abadie ; I. Karen Temple ; Alice Goldenberg ; Veronica Van Heyningen ; Jeanne Amiel ; David Fitzpatrick ; Dirk A. Kleinjan ; Axel Visel ; Stanislas LyonnetSource :
- Human mutation [ 1059-7794 ] ; 2014.
Abstract
Mutations in the coding sequence of
Url:
DOI: 10.1002/humu.22606
PubMed: 24934569
PubMed Central: 4389788
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PMC:4389788Le document en format XML
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Gordon</name><affiliation><nlm:aff id="A1">Université Paris Descartes–Sorbonne Paris Cité, Institut<italic>Imagine</italic>, INSERM U1163, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Attanasio, Catia" sort="Attanasio, Catia" uniqKey="Attanasio C" first="Catia" last="Attanasio">Catia Attanasio</name><affiliation><nlm:aff id="A2">Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Bhatia, Shipra" sort="Bhatia, Shipra" uniqKey="Bhatia S" first="Shipra" last="Bhatia">Shipra Bhatia</name><affiliation><nlm:aff id="A4">MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Benko, Sabina" sort="Benko, Sabina" uniqKey="Benko S" first="Sabina" last="Benko">Sabina Benko</name><affiliation><nlm:aff id="A1">Université Paris Descartes–Sorbonne Paris Cité, Institut<italic>Imagine</italic>, INSERM U1163, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Department of Structural and Chemical Biology, Ichan School of Medicine at Mount Sinai, New York, USA.</nlm:aff></affiliation></author><author><name sortKey="Ansari, Morad" sort="Ansari, Morad" uniqKey="Ansari M" first="Morad" last="Ansari">Morad Ansari</name><affiliation><nlm:aff id="A4">MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Tan, Tiong Y" sort="Tan, Tiong Y" uniqKey="Tan T" first="Tiong Y." last="Tan">Tiong Y. Tan</name><affiliation><nlm:aff id="A6">Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.</nlm:aff></affiliation></author><author><name sortKey="Munnich, Arnold" sort="Munnich, Arnold" uniqKey="Munnich A" first="Arnold" last="Munnich">Arnold Munnich</name><affiliation><nlm:aff id="A1">Université Paris Descartes–Sorbonne Paris Cité, Institut<italic>Imagine</italic>, INSERM U1163, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Hôpital Necker-Enfants Malades AP-HP, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Pennacchio, Len A" sort="Pennacchio, Len A" uniqKey="Pennacchio L" first="Len A." last="Pennacchio">Len A. Pennacchio</name><affiliation><nlm:aff id="A2">Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A8">U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Abadie, Veronique" sort="Abadie, Veronique" uniqKey="Abadie V" first="Véronique" last="Abadie">Véronique Abadie</name><affiliation><nlm:aff id="A9">Service de Pédiatrie Générale, Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Temple, I Karen" sort="Temple, I Karen" uniqKey="Temple I" first="I. Karen" last="Temple">I. Karen Temple</name><affiliation><nlm:aff id="A10">Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Goldenberg, Alice" sort="Goldenberg, Alice" uniqKey="Goldenberg A" first="Alice" last="Goldenberg">Alice Goldenberg</name><affiliation><nlm:aff id="A11">Service de Génétique Médicale, CHU Charles Nicolle, Rouen, France.</nlm:aff></affiliation></author><author><name sortKey="Van Heyningen, Veronica" sort="Van Heyningen, Veronica" uniqKey="Van Heyningen V" first="Veronica" last="Van Heyningen">Veronica Van Heyningen</name><affiliation><nlm:aff id="A4">MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Amiel, Jeanne" sort="Amiel, Jeanne" uniqKey="Amiel J" first="Jeanne" last="Amiel">Jeanne Amiel</name><affiliation><nlm:aff id="A1">Université Paris Descartes–Sorbonne Paris Cité, Institut<italic>Imagine</italic>, INSERM U1163, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Hôpital Necker-Enfants Malades AP-HP, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Fitzpatrick, David" sort="Fitzpatrick, David" uniqKey="Fitzpatrick D" first="David" last="Fitzpatrick">David Fitzpatrick</name><affiliation><nlm:aff id="A4">MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Kleinjan, Dirk A" sort="Kleinjan, Dirk A" uniqKey="Kleinjan D" first="Dirk A." last="Kleinjan">Dirk A. Kleinjan</name><affiliation><nlm:aff id="A4">MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Visel, Axel" sort="Visel, Axel" uniqKey="Visel A" first="Axel" last="Visel">Axel Visel</name><affiliation><nlm:aff id="A2">Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A8">U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A12">School of Natural Sciences, University of California, Merced, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Lyonnet, Stanislas" sort="Lyonnet, Stanislas" uniqKey="Lyonnet S" first="Stanislas" last="Lyonnet">Stanislas Lyonnet</name><affiliation><nlm:aff id="A1">Université Paris Descartes–Sorbonne Paris Cité, Institut<italic>Imagine</italic>, INSERM U1163, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Hôpital Necker-Enfants Malades AP-HP, Paris, France.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24934569</idno><idno type="pmc">4389788</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389788</idno><idno type="RBID">PMC:4389788</idno><idno type="doi">10.1002/humu.22606</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">003935</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003935</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Identification of novel craniofacial regulatory domains located far upstream of <italic>SOX9</italic> and disrupted in Pierre Robin sequence</title><author><name sortKey="Gordon, Christopher T" sort="Gordon, Christopher T" uniqKey="Gordon C" first="Christopher T." last="Gordon">Christopher T. Gordon</name><affiliation><nlm:aff id="A1">Université Paris Descartes–Sorbonne Paris Cité, Institut<italic>Imagine</italic>, INSERM U1163, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Attanasio, Catia" sort="Attanasio, Catia" uniqKey="Attanasio C" first="Catia" last="Attanasio">Catia Attanasio</name><affiliation><nlm:aff id="A2">Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Switzerland.</nlm:aff></affiliation></author><author><name sortKey="Bhatia, Shipra" sort="Bhatia, Shipra" uniqKey="Bhatia S" first="Shipra" last="Bhatia">Shipra Bhatia</name><affiliation><nlm:aff id="A4">MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Benko, Sabina" sort="Benko, Sabina" uniqKey="Benko S" first="Sabina" last="Benko">Sabina Benko</name><affiliation><nlm:aff id="A1">Université Paris Descartes–Sorbonne Paris Cité, Institut<italic>Imagine</italic>, INSERM U1163, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Department of Structural and Chemical Biology, Ichan School of Medicine at Mount Sinai, New York, USA.</nlm:aff></affiliation></author><author><name sortKey="Ansari, Morad" sort="Ansari, Morad" uniqKey="Ansari M" first="Morad" last="Ansari">Morad Ansari</name><affiliation><nlm:aff id="A4">MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Tan, Tiong Y" sort="Tan, Tiong Y" uniqKey="Tan T" first="Tiong Y." last="Tan">Tiong Y. Tan</name><affiliation><nlm:aff id="A6">Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.</nlm:aff></affiliation></author><author><name sortKey="Munnich, Arnold" sort="Munnich, Arnold" uniqKey="Munnich A" first="Arnold" last="Munnich">Arnold Munnich</name><affiliation><nlm:aff id="A1">Université Paris Descartes–Sorbonne Paris Cité, Institut<italic>Imagine</italic>, INSERM U1163, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Hôpital Necker-Enfants Malades AP-HP, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Pennacchio, Len A" sort="Pennacchio, Len A" uniqKey="Pennacchio L" first="Len A." last="Pennacchio">Len A. Pennacchio</name><affiliation><nlm:aff id="A2">Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A8">U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Abadie, Veronique" sort="Abadie, Veronique" uniqKey="Abadie V" first="Véronique" last="Abadie">Véronique Abadie</name><affiliation><nlm:aff id="A9">Service de Pédiatrie Générale, Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Temple, I Karen" sort="Temple, I Karen" uniqKey="Temple I" first="I. Karen" last="Temple">I. Karen Temple</name><affiliation><nlm:aff id="A10">Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Goldenberg, Alice" sort="Goldenberg, Alice" uniqKey="Goldenberg A" first="Alice" last="Goldenberg">Alice Goldenberg</name><affiliation><nlm:aff id="A11">Service de Génétique Médicale, CHU Charles Nicolle, Rouen, France.</nlm:aff></affiliation></author><author><name sortKey="Van Heyningen, Veronica" sort="Van Heyningen, Veronica" uniqKey="Van Heyningen V" first="Veronica" last="Van Heyningen">Veronica Van Heyningen</name><affiliation><nlm:aff id="A4">MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Amiel, Jeanne" sort="Amiel, Jeanne" uniqKey="Amiel J" first="Jeanne" last="Amiel">Jeanne Amiel</name><affiliation><nlm:aff id="A1">Université Paris Descartes–Sorbonne Paris Cité, Institut<italic>Imagine</italic>, INSERM U1163, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Hôpital Necker-Enfants Malades AP-HP, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Fitzpatrick, David" sort="Fitzpatrick, David" uniqKey="Fitzpatrick D" first="David" last="Fitzpatrick">David Fitzpatrick</name><affiliation><nlm:aff id="A4">MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Kleinjan, Dirk A" sort="Kleinjan, Dirk A" uniqKey="Kleinjan D" first="Dirk A." last="Kleinjan">Dirk A. Kleinjan</name><affiliation><nlm:aff id="A4">MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</nlm:aff></affiliation></author><author><name sortKey="Visel, Axel" sort="Visel, Axel" uniqKey="Visel A" first="Axel" last="Visel">Axel Visel</name><affiliation><nlm:aff id="A2">Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A8">U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, USA.</nlm:aff></affiliation><affiliation><nlm:aff id="A12">School of Natural Sciences, University of California, Merced, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Lyonnet, Stanislas" sort="Lyonnet, Stanislas" uniqKey="Lyonnet S" first="Stanislas" last="Lyonnet">Stanislas Lyonnet</name><affiliation><nlm:aff id="A1">Université Paris Descartes–Sorbonne Paris Cité, Institut<italic>Imagine</italic>, INSERM U1163, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Hôpital Necker-Enfants Malades AP-HP, Paris, France.</nlm:aff></affiliation></author></analytic><series><title level="j">Human mutation</title><idno type="ISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Mutations in the coding sequence of <italic>SOX9</italic> cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions and duplications within a ~2 Mb region upstream of <italic>SOX9</italic> can recapitulate the CD-DSD phenotype fully or partially, suggesting the existence of an unusually large cis-regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus for isolated PRS at ~1.2-1.5 Mb upstream of <italic>SOX9</italic> has been previously reported. The craniofacial regulatory potential within this locus, and within the greater genomic domain surrounding <italic>SOX9</italic>, remains poorly defined. We report two novel deletions upstream of <italic>SOX9</italic> in families with PRS, allowing refinement of the regions harbouring candidate craniofacial regulatory elements. In parallel, ChIP-Seq for p300 binding sites in mouse craniofacial tissue led to the identification of several novel craniofacial enhancers at the <italic>SOX9</italic> locus, which were validated in transgenic reporter mice and zebrafish. Notably, some of the functionally validated elements fall within the PRS deletions. These studies suggest that multiple non-coding elements contribute to the craniofacial regulation of <italic>SOX9</italic> expression, and that their disruption results in PRS.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9215429</journal-id><journal-id journal-id-type="pubmed-jr-id">2408</journal-id><journal-id journal-id-type="nlm-ta">Hum Mutat</journal-id><journal-id journal-id-type="iso-abbrev">Hum. Mutat.</journal-id><journal-title-group><journal-title>Human mutation</journal-title></journal-title-group><issn pub-type="ppub">1059-7794</issn><issn pub-type="epub">1098-1004</issn></journal-meta><article-meta><article-id pub-id-type="pmid">24934569</article-id><article-id pub-id-type="pmc">4389788</article-id><article-id pub-id-type="doi">10.1002/humu.22606</article-id><article-id pub-id-type="manuscript">NIHMS675991</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Identification of novel craniofacial regulatory domains located far upstream of <italic>SOX9</italic> and disrupted in Pierre Robin sequence</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gordon</surname><given-names>Christopher T.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="corresp" rid="CR1">#</xref></contrib><contrib contrib-type="author"><name><surname>Attanasio</surname><given-names>Catia</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Bhatia</surname><given-names>Shipra</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Benko</surname><given-names>Sabina</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Ansari</surname><given-names>Morad</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Tan</surname><given-names>Tiong Y.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Munnich</surname><given-names>Arnold</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Pennacchio</surname><given-names>Len A.</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Abadie</surname><given-names>Véronique</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Temple</surname><given-names>I. Karen</given-names></name><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Goldenberg</surname><given-names>Alice</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>van Heyningen</surname><given-names>Veronica</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Amiel</surname><given-names>Jeanne</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>FitzPatrick</surname><given-names>David</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Kleinjan</surname><given-names>Dirk A.</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Visel</surname><given-names>Axel</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Lyonnet</surname><given-names>Stanislas</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="corresp" rid="CR1">#</xref></contrib></contrib-group><aff id="A1"><label>1</label>Université Paris Descartes–Sorbonne Paris Cité, Institut<italic>Imagine</italic>, INSERM U1163, Paris, France.</aff><aff id="A2"><label>2</label>Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.</aff><aff id="A3"><label>3</label>Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Switzerland.</aff><aff id="A4"><label>4</label>MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</aff><aff id="A5"><label>5</label>Department of Structural and Chemical Biology, Ichan School of Medicine at Mount Sinai, New York, USA.</aff><aff id="A6"><label>6</label>Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.</aff><aff id="A7"><label>7</label>Hôpital Necker-Enfants Malades AP-HP, Paris, France.</aff><aff id="A8"><label>8</label>U.S. Department of Energy Joint Genome Institute, Walnut Creek, California, USA.</aff><aff id="A9"><label>9</label>Service de Pédiatrie Générale, Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris, France.</aff><aff id="A10"><label>10</label>Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.</aff><aff id="A11"><label>11</label>Service de Génétique Médicale, CHU Charles Nicolle, Rouen, France.</aff><aff id="A12"><label>12</label>School of Natural Sciences, University of California, Merced, California, USA.</aff><author-notes><corresp id="CR1"><label>#</label> - <bold>Corresponding authors:</bold> CTG and SL INSERM U1163 Institut Imagine, 24 Boulevard du Montparnasse, 75015, Paris France. <email>chris.gordon@inserm.fr</email>, <email>stanislas.lyonnet@inserm.fr</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>1</day><month>4</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>8</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>8</month><year>2015</year></pub-date><volume>35</volume><issue>8</issue><fpage>1011</fpage><lpage>1020</lpage><pmc-comment>elocation-id from pubmed: 10.1002/humu.22606</pmc-comment>
<abstract><p id="P1">Mutations in the coding sequence of <italic>SOX9</italic> cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions and duplications within a ~2 Mb region upstream of <italic>SOX9</italic> can recapitulate the CD-DSD phenotype fully or partially, suggesting the existence of an unusually large cis-regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus for isolated PRS at ~1.2-1.5 Mb upstream of <italic>SOX9</italic> has been previously reported. The craniofacial regulatory potential within this locus, and within the greater genomic domain surrounding <italic>SOX9</italic>, remains poorly defined. We report two novel deletions upstream of <italic>SOX9</italic> in families with PRS, allowing refinement of the regions harbouring candidate craniofacial regulatory elements. In parallel, ChIP-Seq for p300 binding sites in mouse craniofacial tissue led to the identification of several novel craniofacial enhancers at the <italic>SOX9</italic> locus, which were validated in transgenic reporter mice and zebrafish. Notably, some of the functionally validated elements fall within the PRS deletions. These studies suggest that multiple non-coding elements contribute to the craniofacial regulation of <italic>SOX9</italic> expression, and that their disruption results in PRS.</p></abstract><kwd-group><kwd><italic>SOX9</italic></kwd><kwd>craniofacial</kwd><kwd>enhancer</kwd><kwd>Pierre Robin</kwd><kwd>long-range regulation</kwd><kwd>campomelic dysplasia</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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