Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Identification of microdeletions in candidate genes for cleft lip and/or palate

Identification of microdeletions in candidate genes for cleft lip and/or palate 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. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Birth Defects Research Part A Wiley

Identification of microdeletions in candidate genes for cleft lip and/or palate

Download PDF
10 pages

Loading next page...
 
/lp/wiley/identification-of-microdeletions-in-candidate-genes-for-cleft-lip-and-59a6ALaHBg

References (25)

Publisher
Wiley
Copyright
Copyright © 2009 Wiley‐Liss, Inc., A Wiley Company
ISSN
1542-0752
eISSN
1542-0760
DOI
10.1002/bdra.20571
pmid
19137569
Publisher site
See Article on Publisher Site

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. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.

Journal

Birth Defects Research Part A – Wiley

Published: Jan 1, 2009

Keywords: cleft lip; cleft palate; microdeletion; SNP; CNV; candidate genes

There are no references for this article.