Title

Candidate gene/loci studies in cleft lip/palate and dental anomalies finds novel susceptibility genes for clefts

Document Type

Article

Peer Reviewed

1

Publication Date

9-1-2008

Journal, Book or Conference Title

Genetics in medicine

NLM Title Abbreviation

Genet Med

PubMed ID

18978678

DOI

10.1097/GIM.0b013e3181833793

Abstract

PURPOSE: We revisited 42 families with two or more cleft-affected siblings who participated in previous studies. Complete dental information was collected to test the hypothesis that dental anomalies are part of the cleft phenotype spectrum, and can provide new opportunities for identification of cleft susceptibility genes. METHODS: Genotypes from 1489 single nucleotide polymorphism markers located in 150 candidate genes/loci were reanalyzed. Two sets of association analyses were carried out. First, we ran the analysis solely on the cleft status. Second, we assigned affection to any cleft or dental anomaly (tooth agenesis, supernumerary teeth, and microdontia) and repeated the analysis. RESULTS: Significant over-transmission was seen for a single nucleotide polymorphism in ankyrin repeat and sterile alpha motif domain containing 6 (rs4742741, 9q22.33; P = 0.0004) when a dental anomaly phenotype was included in the analysis. Significant over-transmission was also seen for a single nucleotide polymorphism in ERBB2 (rs1810132, 17q21.1; P = 0.0006). In the clefts only data, the most significant result was also for ERBB2 (P = 0.0006). Other markers with suggestive P values included interferon regulatory factor 6 and 6q21-q23 loci. In contrast to the above results, suggestive over-transmission of markers in GART, DPF3, and neurexin 3 were seen only when the dental anomaly phenotype was included in the analysis. CONCLUSIONS: These findings support the hypothesis that some loci may contribute to both clefts and congenital dental anomalies. Thus, including dental anomalies information in the genetics analysis of cleft lip and palate will provide new opportunities to map susceptibility loci for clefts.

Keywords

Cleft Lip/genetics, Cleft Palate/genetics, Genome, Human, Genotype, Humans, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide, Tooth Abnormalities/genetics

Published Article/Book Citation

The definitive version was published in Genetics in medicine, 10:9 (2008) pp.668-674. DOI:10.1097/GIM.0b013e3181833793.

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URL

http://ir.uiowa.edu/nursing_pubs/776