{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T03:19:51Z","timestamp":1771298391323,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,3,5]],"date-time":"2013-03-05T00:00:00Z","timestamp":1362441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Following recent genome wide association studies (GWAS), significant genetic associations have been identified for several genes with nonsyndromic cleft lip with or without cleft palate (CL(P)). To replicate two of these GWAS signals, we investigated the role of common and rare variants in the<jats:italic>PAX7<\/jats:italic>and<jats:italic>VAX1<\/jats:italic>genes. TaqMan genotyping was carried out for SNPs in<jats:italic>VAX1<\/jats:italic>and<jats:italic>PAX7<\/jats:italic>and transmission disequilibrium test (TDT) was performed to test for linkage and association in each population. Direct sequencing in and around the<jats:italic>PAX7<\/jats:italic>and<jats:italic>VAX1<\/jats:italic>genes in 1,326 individuals of European and Asian ancestry was done. The TDT analysis showed strong associations with markers in<jats:italic>VAX1<\/jats:italic>(rs7078160,<jats:italic>P<\/jats:italic>\u2009=\u20092.7E\u221206 and rs475202,<jats:italic>P<\/jats:italic>\u2009=\u20090.0002) in a combined sample of Mongolian and Japanese CL(P) case\u2013parent triads. Analyses using parent\u2010of\u2010origin effects showed significant excess transmission of the minor allele from both parents with the effect in the mothers (<jats:italic>P<\/jats:italic>\u2009=\u20096.5E\u221205, OR (transmission)\u2009=\u20091.91) more striking than in the fathers (<jats:italic>P<\/jats:italic>\u2009=\u20090.004, OR (transmission)\u2009=\u20091.67) for<jats:italic>VAX1<\/jats:italic>marker rs7078160 in the combined Mongolian and Japanese samples when all cleft types were combined. The rs6659735 trinucleotide marker in<jats:italic>PAX7<\/jats:italic>was significantly associated with all the US cleft groups combined (<jats:italic>P<\/jats:italic>\u2009=\u20090.007 in all clefts and<jats:italic>P<\/jats:italic>\u2009=\u20090.02 in CL(P)). Eight rare missense mutations found in<jats:italic>PAX7<\/jats:italic>and two rare missense mutations in<jats:italic>VAX1<\/jats:italic>. Our study replicated previous GWAS findings for markers in<jats:italic>VAX1<\/jats:italic>in the Asian population, and identified rare variants in<jats:italic>PAX7<\/jats:italic>and<jats:italic>VAX1<\/jats:italic>that may contribute to the etiology of CL(P). Determining the role of rare variants clearly warrants further investigation. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.35749","type":"journal-article","created":{"date-parts":[[2013,3,6]],"date-time":"2013-03-06T04:33:23Z","timestamp":1362544403000},"page":"965-972","source":"Crossref","is-referenced-by-count":62,"title":["Replication of Genome Wide Association Identified Candidate Genes Confirm the Role of Common and Rare Variants in<scp><i>PAX<\/i><\/scp><i>7<\/i>and<scp><i>VAX<\/i><\/scp><i>1<\/i>in the Etiology of Nonsyndromic CL(P)"],"prefix":"10.1002","volume":"161","author":[{"given":"Azeez","family":"Butali","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City, Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City, Iowa"},{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies School of Dentistry, Aichi\u2010Gakuin University Japan"},{"name":"Faculty of Psychological and Physical Science Aichi\u2010Gakuin University Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret E.","family":"Cooper","sequence":"additional","affiliation":[{"name":"School of Public Health, Johns Hopkins University Baltimore, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela M.","family":"Mansilla","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City, Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Cuenco","sequence":"additional","affiliation":[{"name":"School of Public Health, Johns Hopkins University Baltimore, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth J.","family":"Leslie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City, Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies School of Dentistry, Aichi\u2010Gakuin University Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruyuki","family":"Niimi","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies School of Dentistry, Aichi\u2010Gakuin University Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Faculty of Psychological and Physical Science Aichi\u2010Gakuin University Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gongorjav","family":"Ayanga","sequence":"additional","affiliation":[{"name":"Maternal and Children's Health Research Center Hospital Ulaanbaatar Mongolia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tudevdorj","family":"Erkhembaatar","sequence":"additional","affiliation":[{"name":"Maternal and Children's Health Research Center Hospital Ulaanbaatar Mongolia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroo","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies School of Dentistry, Aichi\u2010Gakuin University Japan"},{"name":"Faculty of Psychological and Physical Science Aichi\u2010Gakuin University Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumiko","family":"Fujiwawa","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies School of Dentistry, Aichi\u2010Gakuin University Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideto","family":"Imura","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies School of Dentistry, Aichi\u2010Gakuin University Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline L.","family":"Petrin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City, Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagato","family":"Natsume","sequence":"additional","affiliation":[{"name":"Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies School of Dentistry, Aichi\u2010Gakuin University Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terri H.","family":"Beaty","sequence":"additional","affiliation":[{"name":"Department of Oral Biology School of Dental Medicine, Center for Craniofacial and Dental 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