Journal article
Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridization
Journal of medical genetics, Vol.45(2), pp.81-86
02/2008
DOI: 10.1136/jmg.2007.052191
PMCID: PMC3732463
PMID: 17873121
Abstract
Aim and method: We analysed DNA samples isolated from individuals born with cleft lip and cleft palate to identify deletions and duplications of candidate gene loci using array comparative genomic hybridisation (array-CGH).
Results: Of 83 syndromic cases analysed we identified one subject with a previously unknown 2.7 Mb deletion at 22q11.21 coinciding with the DiGeorge syndrome region. Eighteen of the syndromic cases had clinical features of Van der Woude syndrome and deletions were identified in five of these, all of which encompassed the interferon regulatory factor 6 (IRF6) gene. In a series of 104 non-syndromic cases we found one subject with a 3.2 Mb deletion at chromosome 6q25.1-25.2 and another with a 2.2 Mb deletion at 10q26.11-26.13. Analyses of parental DNA demonstrated that the two deletion cases at 22q11.21 and 6q25.1-25.2 were de novo, while the deletion of 10q26.11-26.13 was inherited from the mother, who also has a cleft lip. These deletions appear likely to be causally associated with the phenotypes of the subjects. Estrogen receptor 1 (ESR1) and fibroblast growth factor receptor 2 (FGFR2) genes from the 6q25.1-25.2 and 10q26.11-26.13, respectively, were identified as likely causative genes using a gene prioritization software.
Conclusion: We have shown that array-CGH analysis of DNA samples derived from cleft lip and palate subjects is an efficient and productive method for identifying candidate chromosomal loci and genes, complementing traditional genetic mapping strategies.
Details
- Title: Subtitle
- Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridization
- Creators
- Kazutoyo Osoegawa - Center for Genetics, Children’s Hospital Oakland Research Institute, Children’s Hospital and Research Center Oakland, Oakland CA 94609 USAGery M Vessere - Center for Genetics, Children’s Hospital Oakland Research Institute, Children’s Hospital and Research Center Oakland, Oakland CA 94609 USAKagistia Hana Utami - Center for Genetics, Children’s Hospital Oakland Research Institute, Children’s Hospital and Research Center Oakland, Oakland CA 94609 USAMaria Adela Mansilla - Department of Pediatrics, University of Iowa, Iowa City, IA 52242 USAMarla K Johnson - Department of Pediatrics, University of Iowa, Iowa City, IA 52242 USABridget M Riley - Department of Pediatrics, University of Iowa, Iowa City, IA 52242 USAJamie L’Heureux - Department of Pediatrics, University of Iowa, Iowa City, IA 52242 USARolph Pfundt - Department of Human Genetics, Radboud University Nijmegen Medical Centre, and Nijmegen Center for Molecular Life Sciences, Nijmegen, The NetherlandsJohan Staaf - Department of Oncology, Lund University, SwedenWalter A van der Vliet - Department of Human Genetics, Radboud University Nijmegen Medical Centre, and Nijmegen Center for Molecular Life Sciences, Nijmegen, The NetherlandsAndrew C Lidral - Department of Orthodontics, University of Iowa, Iowa City, IA 52242 USAEric F. P. M Schoenmakers - Department of Human Genetics, Radboud University Nijmegen Medical Centre, and Nijmegen Center for Molecular Life Sciences, Nijmegen, The NetherlandsAke Borg - Department of Oncology, Lund University, SwedenBrian C Schutte - Department of Pediatrics, University of Iowa, Iowa City, IA 52242 USAEdward J Lammer - Center for Genetics, Children’s Hospital Oakland Research Institute, Children’s Hospital and Research Center Oakland, Oakland CA 94609 USAJeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, IA 52242 USAPieter J de Jong - Center for Genetics, Children’s Hospital Oakland Research Institute, Children’s Hospital and Research Center Oakland, Oakland CA 94609 USA
- Resource Type
- Journal article
- Publication Details
- Journal of medical genetics, Vol.45(2), pp.81-86
- DOI
- 10.1136/jmg.2007.052191
- PMID
- 17873121
- PMCID
- PMC3732463
- NLM abbreviation
- J Med Genet
- ISSN
- 0022-2593
- eISSN
- 1468-6244
- Grant note
- R01 DE014667-08 || DE / National Institute of Dental and Craniofacial Research : NIDCR K02 DE015291-05 || DE / National Institute of Dental and Craniofacial Research : NIDCR R37 DE008559-19 || DE / National Institute of Dental and Craniofacial Research : NIDCR K02 DE015291-04 || DE / National Institute of Dental and Craniofacial Research : NIDCR K02 DE015291-03 || DE / National Institute of Dental and Craniofacial Research : NIDCR R37 DE008559-18 || DE / National Institute of Dental and Craniofacial Research : NIDCR R01 DE014667-01 || DE / National Institute of Dental and Craniofacial Research : NIDCR K02 DE015291-02 || DE / National Institute of Dental and Craniofacial Research : NIDCR K02 DE015291-01 || DE / National Institute of Dental and Craniofacial Research : NIDCR R01 DE014667-06 || DE / National Institute of Dental and Craniofacial Research : NIDCR P50 DE016215-04 || DE / National Institute of Dental and Craniofacial Research : NIDCR R01 DE014667-07 || DE / National Institute of Dental and Craniofacial Research : NIDCR R01 DE014667-05 || DE / National Institute of Dental and Craniofacial Research : NIDCR R01 DE014667-04 || DE / National Institute of Dental and Craniofacial Research : NIDCR R01 DE014667-03 || DE / National Institute of Dental and Craniofacial Research : NIDCR R01 DE014667-02 || DE / National Institute of Dental and Craniofacial Research : NIDCR
- Language
- English
- Date published
- 02/2008
- 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
- 9984025409402771
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