Toby Hughes

Genetic and environmental influences on human dental variation: A critical evaluation of studies involving twins

Utilising data derived from twins and their families, different approaches can be applied to study genetic and environmental influences on human dental variation. The different methods have advantages and limitations and special features of the twinning process are important to consider. Model-fitting approaches have shown that different combinations of additive genetic variance (A), non-additive genetic variance (D), common environmental variance (C), and unique environmental variance (E) contribute to phenotypic variation within the dentition, reflecting different ontogenetic and phylogenetic influences. Epigenetic factors are also proposed as important in explaining differences in the dentitions of monozygotic co-twins. Heritability estimates are high for most tooth size variables, for Carabelli trait and for dental arch dimensions, moderate for intercuspal distances, and low for some occlusal traits. In addition to estimating the contributions of unmeasured genetic and environmental influences to phenotypic variation, structural equation models can also be used to test the effects of measured genetic and environmental factors. Whole-genome linkage analysis, association analysis of putative candidate genes, and whole genome association approaches, now offer exciting opportunities to locate key genes involved in human dental development.

Molar Intercuspal Dimensions: Genetic Input to Phenotypic Variation

Molecular studies indicate that epigenetic events are important in determining how the internal enamel epithelium folds during odontogenesis. Since this process of folding leads to the subsequent arrangement of cusps on molar teeth, we hypothesized that intercuspal distances of human molar teeth would display greater phenotypic variation but lower heritabilities than overall crown diameters. Intercuspal distances and maximum crown diameters were recorded from digitized images of dental casts in 100 monozygotic and 74 dizygotic twin pairs. Intercuspal distances displayed less sexual dimorphism in mean values but greater relative variability and fluctuating asymmetry than overall crown measures. Correlations between intercuspal distances and overall crown measures were low. Models incorporating only environmental effects accounted for observed variation in several intercuspal measures. For those intercuspal variables displaying significant additive genetic variance, estimates of heritability ranged from 43 to 79%, whereas those for overall crown size were higher generally, ranging from 60 to 82%. Our finding of high phenotypic variation in intercuspal distances with only moderate genetic contribution is consistent with substantial epigenetic influence on the progressive folding of the internal enamel epithelium, following formation of the primary and secondary enamel knots.

Genetic, environmental and epigenetic influences on variation in human tooth number, size and shape

The aim of this review is to highlight some key recent developments in studies of tooth number, size and shape that are providing better insights into the roles of genetic, environmental and epigenetic factors in the process of dental development. Advances in molecular genetics are helping to clarify how epigenetic factors influence the spatial and temporal regulation of the complex processes involved in odontogenesis. At the phenotypic level, the development of sophisticated systems for image analysis is enabling new dental phenotypes to be defined. The 2D and 3D data that are generated by these imaging systems can then be analysed with mathematical approaches, such as geometric morphometric analysis. By gathering phenotypic data and DNA from twins, it is now possible to use ‘genome-wide’ association studies and the monozygotic co-twin design to identify important genes in odontogenesis and also to clarify how epigenetic and environmental factors can affect this process. Given that many of the common dental anomalies affecting the human dentition are interrelated, apparently reflecting pleiotropic genetic effects, the discoveries and new directions described in this paper should have important implications for clinical dental practice in the future.

Strong Genetic Control of Emergence of Human Primary Incisors

Our understanding of tooth eruption in humans remains incomplete. We hypothesized that genetic factors contribute significantly to phenotypic variation in the emergence of primary incisors. We applied model-fitting to data from Australian twins to quantify contributions of genetic and environmental factors to variation in timing of the emergence of human primary incisors. There were no significant differences in incisor emergence times between zygosity groups or sexes. Emergence times of maxillary central incisors and mandibular lateral incisors were less variable than those of maxillary lateral incisors and mandibular central incisors. Maxillary lateral incisors displayed significant directional asymmetry, the left side emerging earlier than the right. Variation in timing of the emergence of the primary incisors was under strong genetic control, with a small but significant contribution from the external environment. Estimates of narrow-sense heritability ranged from 82 to 94% in males and 71 to 96% in females.

GENETIC AND PHENOTYPIC RELATIONSHIPS BETWEEN FOOD INTAKE, GROWTH, EFFICIENCY AND BODY COMPOSITION OF MICE POST WEANING AND AT MATURITY

Genetic and phenotypic variation in post-weaning growth, food intake, efficiency and body composition of mice post weaning and at maturity, were examined to determine whether genetic variation in efficiency exists and to predict likely responses to selection for increased food efficiency in post-weaning animals. Genetic variation was found for average daily gain, mid-weight, daily food intake and proportion of body fat both post weaning and at maturity. Residual food intake calculated from phenotypic regression had a heritability of 0·27 (s.e. 0·06) post weaning and 0·24 (s.e. 0·08) at maturity, and was very similar to residual food intake calculated using genetic (co)variances, indicating genetic variation in efficiency exists in post-weaning and mature mice. Although the phenotypic correlation between residual food intake post weaning and at maturity was low (0·29), the genetic correlation was moderate (0·60). This suggests that selection for efficiency in young animals will lead to a correlated improvement in maintenance efficiency of mature animals. Genetic correlation estimates suggest that correlated responses in other traits would include a concomitant decrease in post-weaning food intake, a slight increase in weight at weaning, a slight increase in post-weaning fat proportion and little or no change in post-weaning growth. In mature animals there will be an associated decrease in daily food intake and a slight decrease in mature size and body fat proportion. The results suggest that residual food intake of young animals might be a suitable selection criteria for use in livestock species to improve efficiency in young animals and also in the breeding herd.

Genetic analysis of deciduous tooth size in Australian twins.

Investigations of permanent dental crown size in twins and family groups indicate a high degree of transmissible control, but little is known about the relative contributions of genetic and environmental factors to variation in size of the deciduous (primary) teeth. Here, maximum mesiodistal and buccolingual crown dimensions of maxillary and mandibular primary teeth were measured from dental models of 602 individuals, including 99 monozygous (MZ) twin pairs, 81 dizygous (DZ) same-sex pairs, 41 DZ opposite-sex pairs, and 160 singletons. Data were subjected to univariate genetic analysis with the structural-equation-modelling package, Mx using the normal assumptions of the twin model. A model incorporating additive genetic (A) and unique environmental (E) variation was found to be the most parsimonious for all tooth-size variables. Estimates of heritability for deciduous crown size ranged from 0.62 to 0.91. This study shows that variation in deciduous crown size has a strong genetic component, similar to that observed in the permanent dentition. Further studies are required to determine whether the underlying genetic mechanisms are the same for both deciduous and permanent teeth.

The effect of casein phosphopeptide‐amorphous calcium phosphate on erosive dentine wear

BACKGROUND Erosive tooth wear is a growing concern in clinical dentistry. Our aims were to assess the effect of Tooth Mousse (TM) in managing erosive dentine wear in vitro. METHODS Opposing enamel and dentine specimens from 36 third molar teeth were worn under a load of 100 N for 75 000 cycles in electromechanical tooth wear machines. In experiment 1, TM was applied continuously at the wear interface and the mean dentine wear rate was compared with those of specimens subjected to continuous application of hydrochloric acid (HCl, pH 3.0) and deionized water (DW, pH 6.1) as lubricants. In experiment 2, specimens were subjected to TM application every 1600 cycles at both pH 3.0 and 6.1, and the mean dentine wear rates were compared with those of specimens worn with continuous application of HCl and DW lubricants. RESULTS Dentine wear was reduced significantly with continuous application of TM compared with HCl and DW lubricants. Specimens prepared with continuous TM application displayed smooth wear facets, whereas more pronounced microwear details were observed with HCl and DW lubricants. CONCLUSIONS Both remineralization and lubrication seem to contribute to reduction in dentine wear associated with TM application, although lubrication appears to have a more pronounced effect.

The dentition: the outcomes of morphogenesis leading to variations of tooth number, size and shape

The clinical importance of variations of tooth number, size and shape is seen in many dental disciplines. Early diagnosis allows optimal patient management and treatment planning, with intervention at an appropriate time to prevent complications in development and so reduce later treatment need. Understanding the process of dental morphogenesis and the variations in outcomes is an important contribution to the multidisciplinary clinical team approach to treatment. Tooth number, size and shape are determined during the initiation and morphogenetic stages of odontogenesis. The molecular evidence of repetitive signalling throughout initiation and morphogenesis is reflected clinically in the association of anomalies of number, size and shape. This association has been statistically modelled from epidemiological evidence and confirmed by 2D and 3D measurement of human dental study casts. In individuals with hypodontia, the teeth that are formed are smaller than the population mean and often show reduced and simplified shape. In contrast, in individuals with supernumerary teeth, the other teeth are larger than average and may show an enhanced shape. Clinical observations in humans and studies of laboratory animals gave rise to the concept of morphogenetic fields within the dentition. The findings, which can also be considered as reflecting gene expression territories, have been developed to incorporate field, clone and homeobox theories. The clinical distribution of developmental anomalies tends to follow the pattern of these fields or territories. Improved care for patients with these anomalies will come not only from utilizing a multidisciplinary clinical team but also by expanding the approach to include other relevant scientific disciplines.

Intrauterine Hormone Effects on Tooth Dimensions

The human dentition is a complex adaptive system that is influenced by genetic, epigenetic, and environmental factors. Within this system, is sexual dimorphism related to the growth promotion of the Y chromosome, or to hormonal influences, or both? This study is the first to investigate both primary and permanent tooth sizes in females from opposite-sex dizygotic (DZOS) twin pairs compared with females from dizygotic same-sex (DZSS) and monozygotic (MZ) twin pairs to indicate the influence of intrauterine male hormone, including the initial testosterone surge, on dental development. Serial dental models of the primary, mixed, and permanent dentitions of 134 females from DZOS, DZSS, and MZ twins were examined. Mesiodistal, buccolingual, crown height, and intercuspal dimensions of all primary teeth and selected permanent teeth were determined by image analysis. Univariate and multivariate analyses showed statistically significantly larger crown size in DZOS females in both dentitions, with the crown height dimensions displaying the greatest increase in size. These findings strongly support the Twin Testosterone Transfer (TTT) hypothesis. We propose that the growth-promoting effects of the Y chromosome and intrauterine male hormone levels influence different tooth dimensions and contribute differentially to the sexual dimorphism of human teeth.

Dental phenomics: advancing genotype to phenotype correlations in craniofacial research

The field of dental phenomics provides many opportunities to elucidate the roles of genetic, epigenetic and environmental factors in craniofacial development. To date, research findings have helped to clarify the pathogenesis of many conditions, aiding diagnosis and clinical management. This paper provides an overview of dental phenomics research in some commonly encountered oral diseases in everyday clinical practice, as well as research relating to craniofacial growth and development. Clinically, advances in cariology and periodontology have led to better diagnostic capabilities and treatment provision. In the study of growth and development, important information regarding the varying clinical presentation and pathogenesis of many disorders is now apparent through the accurate quantification of phenotypes. Improvements in two-dimensional (2D) and three-dimensional (3D) imaging and analytical techniques have allowed for accurate dental phenotyping, and efforts are ongoing to apply these in vitro techniques to the in vivo setting. The field of dental phenomics represents an exciting avenue that links research findings to practical application, and collaboration between researcher and clinicians will help advance the field further.