Taurodontism in dental genetics.
Ontology highlight
ABSTRACT:
SUBMITTER: Chetty M
PROVIDER: S-EPMC8270984 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The development of tooth is a highly complex procedure and mastered by specific genetic programs. Genetic alterations, environmental factors, and developmental timing can disturb the execution of these programs, and result in various dental anomalies like hypodontia/oligodontia, and supernumerary teeth, which are commonly seen in our clinical practice. Advances in molecular research enabled the identification of various genes involved in the pathogenesis of dental anomalies. In the near future, it will help provide a more accurate diagnosis and biological-based treatment for these anomalies. In this article, we present the molecular phenomenon of tooth development and the genetics of various dental anomalies.
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Project description:Developmental genetics research on mice provides a relatively sound understanding of the genes necessary and sufficient to make mammalian teeth. However, mouse dentitions are highly derived compared with human dentitions, complicating the application of these insights to human biology. We used quantitative genetic analyses of data from living nonhuman primates and extensive osteological and paleontological collections to refine our assessment of dental phenotypes so that they better represent how the underlying genetic mechanisms actually influence anatomical variation. We identify ratios that better characterize the output of two dental genetic patterning mechanisms for primate dentitions. These two newly defined phenotypes are heritable with no measurable pleiotropic effects. When we consider how these two phenotypes vary across neontological and paleontological datasets, we find that the major Middle Miocene taxonomic shift in primate diversity is characterized by a shift in these two genetic outputs. Our results build on the mouse model by combining quantitative genetics and paleontology, and thereby elucidate how genetic mechanisms likely underlie major events in primate evolution.
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Project description:Center for Craniofacial and Dental Genetics (CCDG): Genetics of Orofacial Clefts and Related Phenotypes
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Project description:ObjectiveThe aims of this study were to investigate and compare the prevalence of dental caries and the frequency of oral habits, molar relationships and occlusal traits between children of multiple births, and singletons, and to determine the relative contributions of genetics and environmental factors to these parameters by using twin study design.MethodsThe study group consisted of 345 multiple births (34 monozygotic and 122 dizygotic twin pairs, 11 sets of triplets) and 345 singletons between the ages of 2 and 17. The prevalence of dental caries, and the frequency of tooth brushing, the children's oral habits, molar relationships, and occlusal traits were recorded.ResultsThe percentage of children who brushed their teeth more than twice daily was statistically significantly higher in multiple births than in singletons. Higher correlation coefficients were found in dental caries index, except for decayed, filled (df) (2-5 age group) and filled (f) (6-11 age group), in the monozygotic twin pairs compared to those in the dizygotic twin pairs. In children between the ages of 6 and 11 years, mouth breathing, bruxism, lip biting, and pencil biting were higher in singletons than in children of multiple births. There were statistically significant differences between children of multiple births and singletons, with increased overjet in the 2-5 year age group being observed.ConclusionWhen analyzing these parameters, environmental factors must also be investigated. Due to the low incidence of twin births, longitudinal follow-up studies with more twin pairs are necessary to determine whether these results are generalizable.
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Project description:<p>This study provides an opportunity to investigate the genetics of both dental caries and orofacial clefts (OFCs) in one set of families ascertained in Guatemala. This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>), which was developed through the trans-NIH Genes, Environment, and Health Initiative (GEI). Furthermore this study brings together multiple research priorities of the University of Pittsburgh Center for Craniofacial and Dental Genetics (<a href="http://www.ccdg.pitt.edu" target="_blank">www.ccdg.pitt.edu</a>). A genome-wide panel of 610,000 SNPs was genotyped at the Broad Institute to be comparable to our other pertinent GENEVA studies that are also part of dbGaP (dbGaP accession number <a href="http://www.ncbi.nlm.nih.gov/gap?term=phs000095">phs000095</a>, "Dental Caries: Whole Genome Association and Gene x Environment Studies" and dbGaP accession number <a href="http://www.ncbi.nlm.nih.gov/gap?term=phs000094">phs000094</a>, "International Consortium to Identify Genes and Interactions Controlling Oral Clefts"). The goal of this study is to investigate genetic determinants to dental caries and to OFCs in a novel study population. To date, most genetic studies of dental caries have been conducted in Caucasians, and of OFCs in Caucasians and Asians. The Guatemalan population under study is rural and ethnically mixed with a high proportion of Native-South-Americans.</p> <p>Thirty-six Guatemalans from this dataset were also part of the recent GWAS studies of cleft lip and cleft palate (Beaty et al., 2010 and 2011, dbGaP Study Accession: <a href="http://www.ncbi.nlm.nih.gov/gap?term=phs000094">phs000094</a>, "International Consortium to Identify Genes and Interactions Controlling Oral Clefts"). In addition to the families ascertained in Guatemala, some subjects were genotyped with this cohort to augment the data in the parent GENEVA study (Dental Caries: Whole Genome Association and Gene x Environment Studies, dbGaP accession number <a href="http://www.ncbi.nlm.nih.gov/gap?term=phs000095">phs000095</a>), in particular individuals from the IOWA and PITT GENEVA study sites. Their data are available with the parent study.</p> <p>Dental caries (also known as tooth decay) remains the most common chronic disease of childhood, five times more common than asthma and seven times more common than environmental allergies, with more than 40% of children exhibiting caries when they enter kindergarten. In 2005, it was estimated that dental health care costs were approximately $84 billion, of which 60% or about $50 billion were related to treatment of dental caries. The etiology of dental caries has been studied for many years. Multiple factors contribute to a person's risk for caries, including: 1) environmental factors such as diet, oral hygiene, fluoride exposure and the level of colonization of cariogenic bacteria and 2) host factors such as salivary flow, salivary buffering capacity, position of teeth relative to each other, surface characteristics of tooth enamel and depth of occlusal fissures on posterior teeth. In spite of all that is known about this disease, there are still individuals who appear to be more susceptible to caries and those who are extremely resistant, regardless of the environmental risk factors to which they are exposed, implying that genetic factors also play an important role in caries etiology. This conclusion is supported by studies in both humans and animals, with the most compelling evidence coming from studies of twins reared apart in which investigators found significant resemblance within monozygotic (MZ) but not dizygotic (DZ) twin pairs for percentage of teeth and surfaces restored or carious and estimated the genetic contribution to caries as 40%. Other recent studies of twins reared together estimated the heritability for caries, adjusted for age and gender, as ranging from 45-64%. In our study populations of families, we also estimated caries heritability as approximately 54%-70% of variation in primary dentition caries scores and 35%-55% in the permanent dentition (Wang et al., 2010).</p> <p>Orofacial clefts (OFCs), particularly cleft lip with or without cleft palate (CL/P) and isolated cleft palate (CP) are a major public health problem, affecting one in every 500-1000 births worldwide thus representing the most common facial birth defect and one of the most common of all congenital anomalies. CL/P is a major structural birth defect that is notable for significant lifelong morbidity and complex etiology. The extensive psychological, surgical, speech and dental involvement emphasize the importance of understanding the underlying causes of CL/P. Therefore, many research groups have attempted to elucidate the etiology of CL/P, with some recent success by our research group and others (see Beaty et al., 2010, 2011; Dixon et al., 2011). It is clear that CL/P can occur as part of Mendelian syndromes, that certain chromosomal abnormalities include CL/P in the phenotype, and that certain teratogens can increase the risk of having an offspring with CL/P. However, phenotypes of known etiology comprise only a small portion of all individuals with a CL/P or CP, and the major focus of research into OFCs is to develop an understanding of the etiology of nonsyndromic (NS) forms of clefting. A major focus of the University of Pittsburgh CCDG has been to study additional phenotypes within nonsyndromic OFC families in order to identify sub-clinical expressions of OFC risk genes or risk variants, e.g. SNPs (see Weinberg et al., 2006). A detailed oral exam is conducted as part of these extended phenotypic studies, including a dental caries exam.</p> <p>Note that although there are some reports in the literature of higher caries experience in individuals with clefts, the most recent meta-analysis of those literature reports concluded that individuals born with these defects do not have a higher frequency of caries (Hasslöf and Twetman, 2007). Notably, we investigated the association of CL/P and caries in three of our study populations (including part of the Guatemalan population in this GWAS study) and also found no increase in caries rates of CL/P cases versus controls (Jindal et al., 2011).</p> <p>This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>), which was developed through the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to dental caries and oral clefts through large-scale genome-wide association studies of well-characterized Guatemalan families and individuals. Genotyping was performed at the Broad Institute of MIT and Harvard. The study was supported by the National Institute of Dental and Craniofacial Research (NIDCR, U01-DE018903). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.</p>
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