Evidence of Linkage Disequilibrium across the Enamelysin Gene Using SNP Genotyping

*3016 Evidence of Linkage Disequilibrium across the Enamelysin Gene Using SNP Genotyping*
T.C. HART¹, B.S. MAHER¹, M.C. GORRY¹, P.M.A. CORBY², M. MELO FILHO³, P.S. HART¹, and W. BRETZ¹, ¹ University of Pittsburgh, PA, USA, ² University of Pittsburgh and Harvard University, PA, USA, ³ Unimontes, Montes Claros, Brazil Objective: Haplotype based linkage disequilibrium (LD) mapping is a powerful and cost-effective method of gene association research for complex diseases. Little is currently known about linkage disequilibrium across genetic intervals containing genes important in tooth development. We are interested in applying LD mapping to the study of early childhood caries to evaluate genes important in enamel development. The goal of this study was to evaluate evidence for linkage disequilibrium across the enamelysin (matrix enamel proteinase) gene. Methods: Caries and dental phenotypes were assessed in Brazilian twins (aged 1.5-7 years). We genotyped 9 SNPs spanning a 48 kb region containing enamelysin in 63 dizygotic twin pairs and their parents. SNPS were selected for high polymorphism information content, and all were diallelic with minor allele frequencies > 0.25. SNPs were genotyped using the ABI 7900 with TAQMAN MGB probes. Progeny genotypes were used to determine parental haplotypes. We used only unambiguously inferred parental haplotypes for our analyses. We also assumed that all haplotypes were independent. We measured linkage disequilibrium (LD) across the 48kb spanned by these nine markers. Results: We find substantial LD (D' 격 0.70) across all but the most proximal and distal SNPs (SNP #1 and SNP #9). There was not substantial LD between the second SNP (SNP 851 (LD < 0.39)) or the eight SNP (SNP 742 (LD < 0.27)) and any other SNP. Interestingly, 90.5% of the 221 unambiguous complete haplotypes consisted of either the 1-1-1-1-1 or 2-2-2-2-2 haplotype across the SNPs 823 Ħ 825. Conclusion: Given the significant LD that spans this genomic region, we conclude that a subset of the markers in this gene will provide adequate statistical power for genetic association studies in this population. This finding has applications for genetic studies of dental phenotypes. Supported by NIH/NIDCR grants DE 12879 and DE 12920.
Seq #304 - Caries Epidemiology in Children 3:45 PM-5:45 PM, Saturday, 28 June 2003 Svenska Massan F4
Back to the Cariology Research Program Back to the 81st General Session of the International Association for Dental Research (June 25-28, 2003)
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