Journal article
The PDGF-C regulatory region SNP rs28999109 decreases promoter transcriptional activity and is associated with CL/P
European journal of human genetics : EJHG, Vol.17(6), pp.774-784
2009
DOI: 10.1038/ejhg.2008.245
PMCID: PMC2788748
PMID: 19092777
Abstract
Human linkage and association studies suggest a gene(s) for nonsyndromic cleft lip with or without cleft palate (CL/P) on chromosome 4q31–q32 at or near the platelet-derived growth factor-C (PDGF-C) locus. The mouse Pdgfc−/− knockout shows that PDGF-C is essential for palatogenesis. To evaluate the role of PDGF-C in human clefting, we performed sequence analysis and SNP genotyping using 1048 multiplex CL/P families and 1000 case–control samples from multiple geographic origins. No coding region mutations were identified, but a novel −986 C>T SNP (rs28999109) was significantly associated with CL/P (P=0.01) in cases from Chinese families yielding evidence of linkage to 4q31–q32. Significant or near-significant association was also seen for this and several other PDGF-C SNPs in families from the United States, Spain, India, Turkey, China, and Colombia, whereas no association was seen in families from the Philippines, and Guatemala, and case–controls from Brazil. The −986T allele abolished six overlapping potential transcription regulatory motifs. Transfection assays of PDGF-C promoter reporter constructs show that the −986T allele is associated with a significant decrease (up to 80%) of PDGF-C gene promoter activity. This functional polymorphism acting on a susceptible genetic background may represent a component of human CL/P etiology.
Details
- Title: Subtitle
- The PDGF-C regulatory region SNP rs28999109 decreases promoter transcriptional activity and is associated with CL/P
- Creators
- Sun J CHOI - Human Craniofacial Genetic Section, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United StatesMary L MARAZITA - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesSomnya NARAYANAN - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesMaria Adela Mansilla - Department of Pediatrics, University of Iowa, Iowa City, IA, United StatesJosé M GRANJEIRO - Department of Cell and Molecular Biology, Fluminense Federal University, Niterdi, Rio de Janeiro, BrazilAlexandre R VIEIRA - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesAndrew C LIDRAL - Department of Orthodontics, University of Iowa, Iowa City, IA, United StatesJeffrey C MURRAY - Department of Pediatrics, University of Iowa, Iowa City, IA, United StatesThomas C HART - Human Craniofacial Genetic Section, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United StatesP SUZANNE HART - Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United StatesPawel P SULIMA - Human Craniofacial Genetic Section, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United StatesL. Leigh FIELD - Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, CanadaToby GOLDSTEIN MCHENRY - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesManika GOVIL - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesMargaret E COOPER - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesAriadne LETRA - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesRenato MENEZES - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, United States
- Resource Type
- Journal article
- Publication Details
- European journal of human genetics : EJHG, Vol.17(6), pp.774-784
- DOI
- 10.1038/ejhg.2008.245
- PMID
- 19092777
- PMCID
- PMC2788748
- NLM abbreviation
- Eur J Hum Genet
- ISSN
- 1018-4813
- eISSN
- 1476-5438
- Publisher
- Nature Publishing Group; Basingstoke
- Language
- English
- Date published
- 2009
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Iowa Institute of Human Genetics
- Record Identifier
- 9984025452902771
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