Journal article
Identification of Microdeletions in Candidate Genes for Cleft Lip and/or Palate
Birth defects research. A Clinical and molecular teratology, Vol.85(1), pp.42-51
01/2009
DOI: 10.1002/bdra.20571
PMCID: PMC3682790
PMID: 19137569
Abstract
Background: Genome-wide association studies are now used routinely to identify genes implicated in complex traits. The panels used for such analyses can detect single nucleotide polymorphisms and copy number variants, both of which may help to identify small deleted regions of the genome that may contribute to a particular disease.
Methods: We performed a candidate gene analysis involving 1,221 SNPs in 333 candidate genes for orofacial clefting, using 2,823 samples from 725 two- and three-generation families with a proband having cleft lip with or without cleft palate. We used SNP genotyping, DNA sequencing, high-resolution DNA microarray analysis, and long-range PCR to confirm and characterize the deletion events.
Results: This dataset had a high duplicate reproducibility rate (99.98%), high Mendelian consistency rate (99.93%), and low missing data rate (0.55%), which provided a powerful opportunity for deletion detection. Apparent Mendelian inconsistencies between parents and children suggested deletion events in 15 individuals in 11 genomic regions. We confirmed deletions involving CYP1B1, FGF10, SP8, SUMO1, TBX1, TFAP2A, and UGT7A1, including both de novo and familial cases. Deletions of SUMO1, TBX1, and TFAP2A are likely to be etiologic.
Conclusions: These deletions suggest the potential roles of genes or regulatory elements contained within deleted regions in the etiology of clefting. Our analysis took advantage of genotypes from a candidate-gene-based SNP survey and proved to be an efficient analytical approach to interrogate genes potentially involved in clefting. This can serve as a model to find genes playing a role in complex traits in general.
Details
- Title: Subtitle
- Identification of Microdeletions in Candidate Genes for Cleft Lip and/or Palate
- Creators
- Min Shi - Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, MD A3-03, P.O. Box 12233, Research Triangle Park, NC 27709Adrianna Mostowska - Department of Biochemistry and Molecular Biology University of Medical Sciences in 60-781 Poznan, PolandAstanand Jugessur - Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, AustraliaMarla K Johnson - University of Iowa, Carver College of Medicine, Department of Pediatrics, S. Grand Avenue, 2182 ML, Iowa City, Iowa 52242Maria Adela Mansilla - University of Iowa, Carver College of Medicine, Department of Pediatrics, S. Grand Avenue, 2182 ML, Iowa City, Iowa 52242Kaare Christensen - Institute of Public Health, University of Southern Denmark, J.B. Winslows Vej 9, DK-5000 Odense C. DenmarkRolv T Lie - Section for Epidemiology and Medical Statistics, Department of Public Health and Primary Health Care, University of Bergen, Bergen, NorwayAllen J Wilcox - Epidemiology Branch, National Institute of Environmental Health Sciences MD A3-05, PO Box 12233, Research Triangle Park, NC 27709Jeffrey C Murray - University of Iowa, Carver College of Medicine, Department of Pediatrics, S. Grand Avenue, 2182 ML, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Birth defects research. A Clinical and molecular teratology, Vol.85(1), pp.42-51
- DOI
- 10.1002/bdra.20571
- PMID
- 19137569
- PMCID
- PMC3682790
- NLM abbreviation
- Birth Defects Res A Clin Mol Teratol
- ISSN
- 1542-0752
- eISSN
- 1542-0760
- Publisher
- Wiley
- Grant note
- Z99 ES999999 || ES / National Institute of Environmental Health Sciences : NIEHS
- Language
- English
- Date published
- 01/2009
- 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
- 9984025313502771
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