Fine-Mapping of 5q12.1-13.3 Unveils New Genetic Contributors to Caries.
ABSTRACT Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified the interval 5q12.1-5q13.3 as linked to low caries susceptibility in Filipino families. Here we fine-mapped this region in order to identify genetic contributors to caries susceptibility. Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT scores and genotype data of 75 single-nucleotide polymorphisms were evaluated in the Filipino families with the Family-Based Association Test. For replication purposes, a total 1,467 independent subjects from five different populations were analyzed in a case-control format. In the Filipino cohort, statistically significant and borderline associations were found between low caries experience and four genes spanning 13 million base pairs (PART1, ZSWIM6, CCNB1, and BTF3). We were able to replicate these results in some of the populations studied. We detected PART1 and BTF3 expression in whole saliva, and the expression of BTF3 was associated with caries experience. Our results suggest BTF3 may have a functional role in protecting against caries.
Article: Long non-coding RNAs and enhancers.[Show abstract] [Hide abstract]
ABSTRACT: Long non-coding RNAs (ncRNAs) are emerging as important regulatory factors in mammalian genomics. A number of reports within the last 2 years have identified thousands of actively expressed long ncRNA transcripts with distinct properties. The long ncRNAs show differential expression patterns and regulation in a wide variety of cells and tissues, adding significant complexity to the understanding of their biological role. Furthermore, genome-wide studies of transcriptional enhancers based on chromatin modifications and enhancer binding proteins have led to the identification of putative enhancers and provided insight into their tissue-specific regulation of gene expression. In an exciting turn of events, new evidence is indicating that long ncRNAs are associated with enhancer regions and that such non-coding transcription correlate with the increased activity of the neighboring genes. Moreover, additional experiments suggest that enhancer-function can be mediated through a transcribed long ncRNA and that this might be a common function for long ncRNAs. Here, we review recent advances made both in the genome-wide characterization of enhancers and in the identification of new classes of long ncRNAs, and discuss the functional overlap of these two classes of regulatory elements.Current opinion in genetics & development 02/2011; 21(2):194-8. · 8.99 Impact Factor
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ABSTRACT: The 'reared apart' model, eliminating the effect of common environmental factors, is used extensively in twins research. In this study, teeth present (TP), teeth present excluding third molars (TPX3), teeth restored (TR), teeth restored index (TRI), surfaces restored (SR), surfaces restored index (SRI) and surfaces restored or carious (SRCI), were compared in 46 monozygotic (MZ) twin pairs and 22 dizygotic (DZ) twin pairs separated during infancy and raised apart. The dental examination included charting, panoral and bitewing radiographs, study models and a questionnaire. Data were analysed using intraclass correlations (ICC) and analysis of variance (corrected for age and sex). For all characteristics, the MZ pairs showed greater within-pair similarity than DZ pairs. For MZ pairs, the ICC values for the dental characteristics were all statistically significant (p < 0.005): TP, 0.45; TPX3, 0.49; TR, 0.57; TRI, 0.61; SR, 0.46; SRI, 0.67; SRCI, 0.58. For DZ pairs, none of the ICC values reached statistical significance: TP, 0.04; TPX3, 0.11; TR, 0.30; TRI, 0.31; SR, 0.20; SRI, 0.17; SRCI, 0.26. Despite subjects being reared in different environments, receiving different diets and different dental professional care, the MZ findings demonstrated significant genetic variance (45-67%) for the number of teeth present, number of teeth and surfaces restored, and caries present; the DZ data supported this conclusion. These findings provide new evidence for a genetic contribution to dental caries.Archives of Oral Biology 12/1993; 38(11):937-43. · 1.88 Impact Factor
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ABSTRACT: Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.The American Journal of Human Genetics 10/2007; 81(3):559-75. · 10.99 Impact Factor