Genome Scan, Fine-Mapping, and Candidate Gene Analysis of Non-Syndromic Cleft Lip with or without Cleft Palate Reveals Phenotype-Specific Differences in Linkage and Association Results
Identifieur interne : 002E44 ( Pmc/Corpus ); précédent : 002E43; suivant : 002E45Genome Scan, Fine-Mapping, and Candidate Gene Analysis of Non-Syndromic Cleft Lip with or without Cleft Palate Reveals Phenotype-Specific Differences in Linkage and Association Results
Auteurs : Mary L. Marazita ; Andrew C. Lidral ; Jeffrey C. Murray ; L. Leigh Field ; Brion S. Maher ; Toby Goldstein Mchenry ; Margaret E. Cooper ; Manika Govil ; Sandra Daack-Hirsch ; Bridget Riley ; Astanand Jugessur ; Temis Felix ; Lina Morene ; M. Adela Mansilla ; Alexandre R. Vieira ; Kim Doheny ; Elizabeth Pugh ; Consuelo Valencia-Ramirez ; Mauricio Arcos-BurgosSource :
- Human Heredity [ 0001-5652 ] ; 2009.
Abstract
Non-syndromic orofacial clefts, i.e. cleft lip (CL) and cleft palate (CP), are among the most common birth defects. The goal of this study was to identify genomic regions and genes for CL with or without CP (CL/P).
We performed linkage analyses of a 10 cM genome scan in 820 multiplex CL/P families (6,565 individuals). Significant linkage results were followed by association analyses of 1,476 SNPs in candidate genes and regions, utilizing a weighted false discovery rate (wFDR) approach to control for multiple testing and incorporate the genome scan results.
Significant (multipoint HLOD ≥3.2) or genome-wide-significant (HLOD ≥4.02) linkage results were found for regions 1q32, 2p13, 3q27-28, 9q21, 12p11, 14q21-24 and 16q24. SNPs in
These results highlight the importance of careful phenotypic delineation in large samples of families for genetic analyses of complex, heterogeneous traits such as CL/P.
Url:
DOI: 10.1159/000224636
PubMed: 19521098
PubMed Central: 2709160
Links to Exploration step
PMC:2709160Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genome Scan, Fine-Mapping, and Candidate Gene Analysis of Non-Syndromic Cleft Lip with or without Cleft Palate Reveals Phenotype-Specific Differences in Linkage and Association Results</title><author><name sortKey="Marazita, Mary L" sort="Marazita, Mary L" uniqKey="Marazita M" first="Mary L." last="Marazita">Mary L. Marazita</name><affiliation><nlm:aff id="aff1">Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation></author><author><name sortKey="Lidral, Andrew C" sort="Lidral, Andrew C" uniqKey="Lidral A" first="Andrew C." last="Lidral">Andrew C. Lidral</name><affiliation><nlm:aff id="aff5">Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Murray, Jeffrey C" sort="Murray, Jeffrey C" uniqKey="Murray J" first="Jeffrey C." last="Murray">Jeffrey C. Murray</name><affiliation><nlm:aff id="aff6">Department of Pediatrics College of Medicine, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Field, L Leigh" sort="Field, L Leigh" uniqKey="Field L" first="L. Leigh" last="Field">L. Leigh Field</name><affiliation><nlm:aff id="aff9">Department of Medical Genetics, University of British Columbia, and B.C. Research Institute for Children's and Women's Health, Vancouver, BC, Canada</nlm:aff></affiliation></author><author><name sortKey="Maher, Brion S" sort="Maher, Brion S" uniqKey="Maher B" first="Brion S." last="Maher">Brion S. Maher</name><affiliation><nlm:aff id="aff8">Department of Psychiatry, Virginia Commonwealth University, Richmond, Va., USA</nlm:aff></affiliation></author><author><name sortKey="Goldstein Mchenry, Toby" sort="Goldstein Mchenry, Toby" uniqKey="Goldstein Mchenry T" first="Toby" last="Goldstein Mchenry">Toby Goldstein Mchenry</name><affiliation><nlm:aff id="aff1">Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation></author><author><name sortKey="Cooper, Margaret E" sort="Cooper, Margaret E" uniqKey="Cooper M" first="Margaret E." last="Cooper">Margaret E. Cooper</name><affiliation><nlm:aff id="aff1">Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation></author><author><name sortKey="Govil, Manika" sort="Govil, Manika" uniqKey="Govil M" first="Manika" last="Govil">Manika Govil</name><affiliation><nlm:aff id="aff1">Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation></author><author><name sortKey="Daack Hirsch, Sandra" sort="Daack Hirsch, Sandra" uniqKey="Daack Hirsch S" first="Sandra" last="Daack-Hirsch">Sandra Daack-Hirsch</name><affiliation><nlm:aff id="aff7">College of Nursing, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Riley, Bridget" sort="Riley, Bridget" uniqKey="Riley B" first="Bridget" last="Riley">Bridget Riley</name><affiliation><nlm:aff id="aff10">New York University School of Medicine, New York, N.Y., USA</nlm:aff></affiliation></author><author><name sortKey="Jugessur, Astanand" sort="Jugessur, Astanand" uniqKey="Jugessur A" first="Astanand" last="Jugessur">Astanand Jugessur</name><affiliation><nlm:aff id="aff11">Craniofacial Development, Musculoskeletal Disorders, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Felix, Temis" sort="Felix, Temis" uniqKey="Felix T" first="Temis" last="Felix">Temis Felix</name><affiliation><nlm:aff id="aff12">Hospital de Clinicas Porto Allegre-RS, Universidade Federal do Rio Grande do Sul, Brazil</nlm:aff></affiliation></author><author><name sortKey="Morene, Lina" sort="Morene, Lina" uniqKey="Morene L" first="Lina" last="Morene">Lina Morene</name><affiliation><nlm:aff id="aff5">Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Mansilla, M Adela" sort="Mansilla, M Adela" uniqKey="Mansilla M" first="M. Adela" last="Mansilla">M. Adela Mansilla</name><affiliation><nlm:aff id="aff6">Department of Pediatrics College of Medicine, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Vieira, Alexandre R" sort="Vieira, Alexandre R" uniqKey="Vieira A" first="Alexandre R." last="Vieira">Alexandre R. Vieira</name><affiliation><nlm:aff id="aff1">Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Department of Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation></author><author><name sortKey="Doheny, Kim" sort="Doheny, Kim" uniqKey="Doheny K" first="Kim" last="Doheny">Kim Doheny</name><affiliation><nlm:aff id="aff13">Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA</nlm:aff></affiliation></author><author><name sortKey="Pugh, Elizabeth" sort="Pugh, Elizabeth" uniqKey="Pugh E" first="Elizabeth" last="Pugh">Elizabeth Pugh</name><affiliation><nlm:aff id="aff13">Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA</nlm:aff></affiliation></author><author><name sortKey="Valencia Ramirez, Consuelo" sort="Valencia Ramirez, Consuelo" uniqKey="Valencia Ramirez C" first="Consuelo" last="Valencia-Ramirez">Consuelo Valencia-Ramirez</name><affiliation><nlm:aff id="aff14">College of Dentistry, Universidad de Antioquia, Medellin, Colombia, USA</nlm:aff></affiliation></author><author><name sortKey="Arcos Burgos, Mauricio" sort="Arcos Burgos, Mauricio" uniqKey="Arcos Burgos M" first="Mauricio" last="Arcos-Burgos">Mauricio Arcos-Burgos</name><affiliation><nlm:aff id="aff15">Division of Child Psychiatry, Department of Psychiatry and Behavioral Sciences, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla., USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19521098</idno><idno type="pmc">2709160</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709160</idno><idno type="RBID">PMC:2709160</idno><idno type="doi">10.1159/000224636</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">002E44</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E44</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome Scan, Fine-Mapping, and Candidate Gene Analysis of Non-Syndromic Cleft Lip with or without Cleft Palate Reveals Phenotype-Specific Differences in Linkage and Association Results</title><author><name sortKey="Marazita, Mary L" sort="Marazita, Mary L" uniqKey="Marazita M" first="Mary L." last="Marazita">Mary L. Marazita</name><affiliation><nlm:aff id="aff1">Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation></author><author><name sortKey="Lidral, Andrew C" sort="Lidral, Andrew C" uniqKey="Lidral A" first="Andrew C." last="Lidral">Andrew C. Lidral</name><affiliation><nlm:aff id="aff5">Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Murray, Jeffrey C" sort="Murray, Jeffrey C" uniqKey="Murray J" first="Jeffrey C." last="Murray">Jeffrey C. Murray</name><affiliation><nlm:aff id="aff6">Department of Pediatrics College of Medicine, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Field, L Leigh" sort="Field, L Leigh" uniqKey="Field L" first="L. Leigh" last="Field">L. Leigh Field</name><affiliation><nlm:aff id="aff9">Department of Medical Genetics, University of British Columbia, and B.C. Research Institute for Children's and Women's Health, Vancouver, BC, Canada</nlm:aff></affiliation></author><author><name sortKey="Maher, Brion S" sort="Maher, Brion S" uniqKey="Maher B" first="Brion S." last="Maher">Brion S. Maher</name><affiliation><nlm:aff id="aff8">Department of Psychiatry, Virginia Commonwealth University, Richmond, Va., USA</nlm:aff></affiliation></author><author><name sortKey="Goldstein Mchenry, Toby" sort="Goldstein Mchenry, Toby" uniqKey="Goldstein Mchenry T" first="Toby" last="Goldstein Mchenry">Toby Goldstein Mchenry</name><affiliation><nlm:aff id="aff1">Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation></author><author><name sortKey="Cooper, Margaret E" sort="Cooper, Margaret E" uniqKey="Cooper M" first="Margaret E." last="Cooper">Margaret E. Cooper</name><affiliation><nlm:aff id="aff1">Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation></author><author><name sortKey="Govil, Manika" sort="Govil, Manika" uniqKey="Govil M" first="Manika" last="Govil">Manika Govil</name><affiliation><nlm:aff id="aff1">Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation></author><author><name sortKey="Daack Hirsch, Sandra" sort="Daack Hirsch, Sandra" uniqKey="Daack Hirsch S" first="Sandra" last="Daack-Hirsch">Sandra Daack-Hirsch</name><affiliation><nlm:aff id="aff7">College of Nursing, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Riley, Bridget" sort="Riley, Bridget" uniqKey="Riley B" first="Bridget" last="Riley">Bridget Riley</name><affiliation><nlm:aff id="aff10">New York University School of Medicine, New York, N.Y., USA</nlm:aff></affiliation></author><author><name sortKey="Jugessur, Astanand" sort="Jugessur, Astanand" uniqKey="Jugessur A" first="Astanand" last="Jugessur">Astanand Jugessur</name><affiliation><nlm:aff id="aff11">Craniofacial Development, Musculoskeletal Disorders, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia</nlm:aff></affiliation></author><author><name sortKey="Felix, Temis" sort="Felix, Temis" uniqKey="Felix T" first="Temis" last="Felix">Temis Felix</name><affiliation><nlm:aff id="aff12">Hospital de Clinicas Porto Allegre-RS, Universidade Federal do Rio Grande do Sul, Brazil</nlm:aff></affiliation></author><author><name sortKey="Morene, Lina" sort="Morene, Lina" uniqKey="Morene L" first="Lina" last="Morene">Lina Morene</name><affiliation><nlm:aff id="aff5">Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Mansilla, M Adela" sort="Mansilla, M Adela" uniqKey="Mansilla M" first="M. Adela" last="Mansilla">M. Adela Mansilla</name><affiliation><nlm:aff id="aff6">Department of Pediatrics College of Medicine, University of Iowa, Iowa City, Iowa, USA</nlm:aff></affiliation></author><author><name sortKey="Vieira, Alexandre R" sort="Vieira, Alexandre R" uniqKey="Vieira A" first="Alexandre R." last="Vieira">Alexandre R. Vieira</name><affiliation><nlm:aff id="aff1">Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Department of Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</nlm:aff></affiliation></author><author><name sortKey="Doheny, Kim" sort="Doheny, Kim" uniqKey="Doheny K" first="Kim" last="Doheny">Kim Doheny</name><affiliation><nlm:aff id="aff13">Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA</nlm:aff></affiliation></author><author><name sortKey="Pugh, Elizabeth" sort="Pugh, Elizabeth" uniqKey="Pugh E" first="Elizabeth" last="Pugh">Elizabeth Pugh</name><affiliation><nlm:aff id="aff13">Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA</nlm:aff></affiliation></author><author><name sortKey="Valencia Ramirez, Consuelo" sort="Valencia Ramirez, Consuelo" uniqKey="Valencia Ramirez C" first="Consuelo" last="Valencia-Ramirez">Consuelo Valencia-Ramirez</name><affiliation><nlm:aff id="aff14">College of Dentistry, Universidad de Antioquia, Medellin, Colombia, USA</nlm:aff></affiliation></author><author><name sortKey="Arcos Burgos, Mauricio" sort="Arcos Burgos, Mauricio" uniqKey="Arcos Burgos M" first="Mauricio" last="Arcos-Burgos">Mauricio Arcos-Burgos</name><affiliation><nlm:aff id="aff15">Division of Child Psychiatry, Department of Psychiatry and Behavioral Sciences, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla., USA</nlm:aff></affiliation></author></analytic><series><title level="j">Human Heredity</title><idno type="ISSN">0001-5652</idno><idno type="eISSN">1423-0062</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objectives</title><p>Non-syndromic orofacial clefts, i.e. cleft lip (CL) and cleft palate (CP), are among the most common birth defects. The goal of this study was to identify genomic regions and genes for CL with or without CP (CL/P).</p></sec><sec><title>Methods</title><p>We performed linkage analyses of a 10 cM genome scan in 820 multiplex CL/P families (6,565 individuals). Significant linkage results were followed by association analyses of 1,476 SNPs in candidate genes and regions, utilizing a weighted false discovery rate (wFDR) approach to control for multiple testing and incorporate the genome scan results.</p></sec><sec><title>Results</title><p>Significant (multipoint HLOD ≥3.2) or genome-wide-significant (HLOD ≥4.02) linkage results were found for regions 1q32, 2p13, 3q27-28, 9q21, 12p11, 14q21-24 and 16q24. SNPs in <italic>IRF6</italic> (1q32) and in or near <italic>FOXE1</italic> (9q21) reached formal genome-wide wFDR-adjusted significance. Further, results were phenotype dependent in that the <italic>IRF6</italic> region results were most significant for families in which affected individuals have CL alone, and the <italic>FOXE1</italic> region results were most significant in families in which some or all of the affected individuals have CL with CP.</p></sec><sec><title>Conclusions</title><p>These results highlight the importance of careful phenotypic delineation in large samples of families for genetic analyses of complex, heterogeneous traits such as CL/P.</p></sec></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>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Hum Hered</journal-id><journal-id journal-id-type="publisher-id">HHE</journal-id><journal-title-group><journal-title>Human Heredity</journal-title></journal-title-group><issn pub-type="ppub">0001-5652</issn><issn pub-type="epub">1423-0062</issn><publisher><publisher-name>S. Karger AG</publisher-name><publisher-loc>Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">19521098</article-id><article-id pub-id-type="pmc">2709160</article-id><article-id pub-id-type="doi">10.1159/000224636</article-id><article-id pub-id-type="publisher-id">hhe0068-0151</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Paper</subject></subj-group></article-categories><title-group><article-title>Genome Scan, Fine-Mapping, and Candidate Gene Analysis of Non-Syndromic Cleft Lip with or without Cleft Palate Reveals Phenotype-Specific Differences in Linkage and Association Results</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Marazita</surname><given-names>Mary L.</given-names></name><xref ref-type="aff" rid="aff1">a</xref><xref ref-type="aff" rid="aff2">b</xref><xref ref-type="aff" rid="aff3">c</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Lidral</surname><given-names>Andrew C.</given-names></name><xref ref-type="aff" rid="aff5">e</xref></contrib><contrib contrib-type="author"><name><surname>Murray</surname><given-names>Jeffrey C.</given-names></name><xref ref-type="aff" rid="aff6">f</xref></contrib><contrib contrib-type="author"><name><surname>Field</surname><given-names>L.Leigh</given-names></name><xref ref-type="aff" rid="aff9">i</xref></contrib><contrib contrib-type="author"><name><surname>Maher</surname><given-names>Brion S.</given-names></name><xref ref-type="aff" rid="aff8">h</xref></contrib><contrib contrib-type="author"><name><surname>Goldstein McHenry</surname><given-names>Toby</given-names></name><xref ref-type="aff" rid="aff1">a</xref></contrib><contrib contrib-type="author"><name><surname>Cooper</surname><given-names>Margaret E.</given-names></name><xref ref-type="aff" rid="aff1">a</xref></contrib><contrib contrib-type="author"><name><surname>Govil</surname><given-names>Manika</given-names></name><xref ref-type="aff" rid="aff1">a</xref></contrib><contrib contrib-type="author"><name><surname>Daack-Hirsch</surname><given-names>Sandra</given-names></name><xref ref-type="aff" rid="aff7">g</xref></contrib><contrib contrib-type="author"><name><surname>Riley</surname><given-names>Bridget</given-names></name><xref ref-type="aff" rid="aff10">j</xref></contrib><contrib contrib-type="author"><name><surname>Jugessur</surname><given-names>Astanand</given-names></name><xref ref-type="aff" rid="aff11">k</xref></contrib><contrib contrib-type="author"><name><surname>Felix</surname><given-names>Temis</given-names></name><xref ref-type="aff" rid="aff12">l</xref></contrib><contrib contrib-type="author"><name><surname>Morene</surname><given-names>Lina</given-names></name><xref ref-type="aff" rid="aff5">e</xref></contrib><contrib contrib-type="author"><name><surname>Mansilla</surname><given-names>M.Adela</given-names></name><xref ref-type="aff" rid="aff6">f</xref></contrib><contrib contrib-type="author"><name><surname>Vieira</surname><given-names>Alexandre R.</given-names></name><xref ref-type="aff" rid="aff1">a</xref><xref ref-type="aff" rid="aff2">b</xref><xref ref-type="aff" rid="aff4">d</xref></contrib><contrib contrib-type="author"><name><surname>Doheny</surname><given-names>Kim</given-names></name><xref ref-type="aff" rid="aff13">m</xref></contrib><contrib contrib-type="author"><name><surname>Pugh</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="aff13">m</xref></contrib><contrib contrib-type="author"><name><surname>Valencia-Ramirez</surname><given-names>Consuelo</given-names></name><xref ref-type="aff" rid="aff14">n</xref></contrib><contrib contrib-type="author"><name><surname>Arcos-Burgos</surname><given-names>Mauricio</given-names></name><xref ref-type="aff" rid="aff15">o</xref></contrib></contrib-group><aff id="aff1"><sup>a</sup>Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</aff><aff id="aff2"><sup>b</sup>Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa., USA</aff><aff id="aff3"><sup>c</sup>Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</aff><aff id="aff4"><sup>d</sup>Department of Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pa., USA</aff><aff id="aff5"><sup>e</sup>Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, Iowa, USA</aff><aff id="aff6"><sup>f</sup>Department of Pediatrics College of Medicine, University of Iowa, Iowa City, Iowa, USA</aff><aff id="aff7"><sup>g</sup>College of Nursing, University of Iowa, Iowa City, Iowa, USA</aff><aff id="aff8"><sup>h</sup>Department of Psychiatry, Virginia Commonwealth University, Richmond, Va., USA</aff><aff id="aff9"><sup>i</sup>Department of Medical Genetics, University of British Columbia, and B.C. Research Institute for Children's and Women's Health, Vancouver, BC, Canada</aff><aff id="aff10"><sup>j</sup>New York University School of Medicine, New York, N.Y., USA</aff><aff id="aff11"><sup>k</sup>Craniofacial Development, Musculoskeletal Disorders, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia</aff><aff id="aff12"><sup>l</sup>Hospital de Clinicas Porto Allegre-RS, Universidade Federal do Rio Grande do Sul, Brazil</aff><aff id="aff13"><sup>m</sup>Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA</aff><aff id="aff14"><sup>n</sup>College of Dentistry, Universidad de Antioquia, Medellin, Colombia, USA</aff><aff id="aff15"><sup>o</sup>Division of Child Psychiatry, Department of Psychiatry and Behavioral Sciences, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla., USA</aff><author-notes><corresp id="cor1">Mary L. Marazita, PhD, Center for Craniofacial and Dental Genetics, University of Pittsburgh, Suite 500 Bridgeside Point, 100 Technology Dr., Pittsburgh, PA 15219 (USA), Tel. +1 412 648 8380, Fax +1 412 648 8779, E-Mail <email>marazita@pitt.edu</email></corresp></author-notes><pub-date pub-type="ppub"><month>7</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>11</day><month>6</month><year>2009</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>7</month><year>2010</year></pub-date><pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
<volume>68</volume><issue>3</issue><fpage>151</fpage><lpage>170</lpage><history><date date-type="received"><day>02</day><month>12</month><year>2008</year></date><date date-type="accepted"><day>12</day><month>2</month><year>2009</year></date></history><permissions><copyright-statement>Copyright © 2009 by S. Karger AG, Basel</copyright-statement><copyright-year>2009</copyright-year></permissions><abstract><sec><title>Objectives</title><p>Non-syndromic orofacial clefts, i.e. cleft lip (CL) and cleft palate (CP), are among the most common birth defects. The goal of this study was to identify genomic regions and genes for CL with or without CP (CL/P).</p></sec><sec><title>Methods</title><p>We performed linkage analyses of a 10 cM genome scan in 820 multiplex CL/P families (6,565 individuals). Significant linkage results were followed by association analyses of 1,476 SNPs in candidate genes and regions, utilizing a weighted false discovery rate (wFDR) approach to control for multiple testing and incorporate the genome scan results.</p></sec><sec><title>Results</title><p>Significant (multipoint HLOD ≥3.2) or genome-wide-significant (HLOD ≥4.02) linkage results were found for regions 1q32, 2p13, 3q27-28, 9q21, 12p11, 14q21-24 and 16q24. SNPs in <italic>IRF6</italic> (1q32) and in or near <italic>FOXE1</italic> (9q21) reached formal genome-wide wFDR-adjusted significance. Further, results were phenotype dependent in that the <italic>IRF6</italic> region results were most significant for families in which affected individuals have CL alone, and the <italic>FOXE1</italic> region results were most significant in families in which some or all of the affected individuals have CL with CP.</p></sec><sec><title>Conclusions</title><p>These results highlight the importance of careful phenotypic delineation in large samples of families for genetic analyses of complex, heterogeneous traits such as CL/P.</p></sec></abstract><kwd-group><title>Key Words</title><kwd>Cleft lip</kwd><kwd>Cleft palate</kwd><kwd>Linkage</kwd><kwd>Association</kwd><kwd>wFDR</kwd><kwd><italic>IRF6</italic></kwd><kwd><italic>FOXE1</italic></kwd><kwd>Genetics</kwd></kwd-group><counts><fig-count count="4"></fig-count><table-count count="5"></table-count><ref-count count="110"></ref-count><page-count count="20"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002E44 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 002E44 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= LymphedemaV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:2709160
|texte= Genome Scan, Fine-Mapping, and Candidate Gene Analysis of Non-Syndromic Cleft Lip with or without Cleft Palate Reveals Phenotype-Specific Differences in Linkage and Association Results
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:19521098" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a LymphedemaV1
| This area was generated with Dilib version V0.6.31. |  |