Facial shape and allometry quantitative trait locus intervals in the Diversity Outbred mouse are enriched for known skeletal and facial development genes.
ABSTRACT: The biology of how faces are built and come to differ from one another is complex. Discovering normal variants that contribute to differences in facial morphology is one key to untangling this complexity, with important implications for medicine and evolutionary biology. This study maps quantitative trait loci (QTL) for skeletal facial shape using Diversity Outbred (DO) mice. The DO is a randomly outcrossed population with high heterozygosity that captures the allelic diversity of eight inbred mouse lines from three subspecies. The study uses a sample of 1147 DO animals (the largest sample yet employed for a shape QTL study in mouse), each characterized by 22 three-dimensional landmarks, 56,885 autosomal and X-chromosome markers, and sex and age classifiers. We identified 37 facial shape QTL across 20 shape principal components (PCs) using a mixed effects regression that accounts for kinship among observations. The QTL include some previously identified intervals as well as new regions that expand the list of potential targets for future experimental study. Three QTL characterized shape associations with size (allometry). Median support interval size was 3.5 Mb. Narrowing additional analysis to QTL for the five largest magnitude shape PCs, we found significant overrepresentation of genes with known roles in growth, skeletal and facial development, and sensory organ development. For most intervals, one or more of these genes lies within 0.25 Mb of the QTL's peak. QTL effect sizes were small, with none explaining more than 0.5% of facial shape variation. Thus, our results are consistent with a model of facial diversity that is influenced by key genes in skeletal and facial development and, simultaneously, is highly polygenic.
Project description:The regular collection of 3-dimensional (3D) imaging data is critical to the development and implementation of accurate predictive models of facial skeletal growth. However, repeated exposure to x-ray-based modalities such as cone-beam computed tomography has unknown risks that outweigh many potential benefits, especially in pediatric patients. One solution is to make inferences about the facial skeleton from external 3D surface morphology captured using safe nonionizing imaging modalities alone. However, the degree to which external 3D facial shape is an accurate proxy of skeletal morphology has not been previously quantified. As a first step in validating this approach, we tested the hypothesis that population-level variation in the 3D shape of the face and skeleton significantly covaries.We retrospectively analyzed 3D surface and skeletal morphology from a previously collected cross-sectional cone-beam computed tomography database of nonsurgical orthodontics patients and used geometric morphometrics and multivariate statistics to test the hypothesis that shape variation in external face and internal skeleton covaries.External facial morphology is highly predictive of variation in internal skeletal shape ([Rv] = 0.56, P <0.0001; partial least squares [PLS] 1-13 = 98.7% covariance, P <0.001) and asymmetry (Rv = 0.34, P <0.0001; PLS 1-5 = 90.2% covariance, P <0.001), whereas age-related (r(2) = 0.84, P <0.001) and size-related (r(2) = 0.67, P <0.001) shape variation was also highly correlated.Surface morphology is a reliable source of proxy data for the characterization of skeletal shape variation and thus is particularly valuable in research designs where reducing potential long-term risks associated with radiologic imaging methods is warranted. We propose that longitudinal surface morphology from early childhood through late adolescence can be a valuable source of data that will facilitate the development of personalized craniodental and treatment plans and reduce exposure levels to as low as reasonably achievable.
Project description:Several lines of evidence suggest that facial cues of adiposity may be important for human social interaction. However, tests for quantifiable cues of body mass index (BMI) in the face have examined only a small number of facial proportions and these proportions were found to have relatively low predictive power. Here we employed a data-driven approach in which statistical models were built using principal components (PCs) derived from objectively defined shape and color characteristics in face images. The predictive power of these models was then compared with models based on previously studied facial proportions (perimeter-to-area ratio, width-to-height ratio, and cheek-to-jaw width). Models based on 2D shape-only PCs, color-only PCs, and 2D shape and color PCs combined each performed significantly and substantially better than models based on one or more of the previously studied facial proportions. A non-linear PC model considering both 2D shape and color PCs was the best predictor of BMI. These results highlight the utility of a "bottom-up", data-driven approach for assessing BMI from face images.
Project description:Facial expression is a common channel for the communication of emotion. However, in the case of non-human animals, the analytical methods used to quantify facial expressions can be subjective, relying heavily on extrapolation from human-based systems. Here, we demonstrate how geometric morphometrics can be applied in order to overcome these problems. We used this approach to identify and quantify changes in facial shape associated with pain in a non-human animal species. Our method accommodates individual variability, species-specific facial anatomy, and postural effects. Facial images were captured at four different time points during ovariohysterectomy of domestic short haired cats (n?=?29), with time points corresponding to varying intensities of pain. Images were annotated using landmarks specifically chosen for their relationship with underlying musculature, and relevance to cat-specific facial action units. Landmark data were subjected to normalisation before Principal Components (PCs) were extracted to identify key sources of facial shape variation, relative to pain intensity. A significant relationship between PC scores and a well-validated composite measure of post-operative pain in cats (UNESP-Botucatu MCPS tool) was evident, demonstrating good convergent validity between our geometric face model, and other metrics of pain detection. This study lays the foundation for the automatic, objective detection of emotional expressions in a range of non-human animal species.
Project description:Human facial diversity is substantial, complex, and largely scientifically unexplained. We used spatially dense quasi-landmarks to measure face shape in population samples with mixed West African and European ancestry from three locations (United States, Brazil, and Cape Verde). Using bootstrapped response-based imputation modeling (BRIM), we uncover the relationships between facial variation and the effects of sex, genomic ancestry, and a subset of craniofacial candidate genes. The facial effects of these variables are summarized as response-based imputed predictor (RIP) variables, which are validated using self-reported sex, genomic ancestry, and observer-based facial ratings (femininity and proportional ancestry) and judgments (sex and population group). By jointly modeling sex, genomic ancestry, and genotype, the independent effects of particular alleles on facial features can be uncovered. Results on a set of 20 genes showing significant effects on facial features provide support for this approach as a novel means to identify genes affecting normal-range facial features and for approximating the appearance of a face from genetic markers.
Project description:Wrinkles are uneven concave-convex folds, ridges or creases in skin. Facial wrinkles appear in head, typically increasing along with aging. However in several Chinese indigenous pigs, such as Erhualian pigs, rich facial wrinkles have been generated during the growth stages as one of their breed characteristics. To investigate the genetic basis underlying the development of swine facial wrinkles, we estimated the folding extent of facial wrinkles in a herd of Erhualian pigs (n=332), and then conducted genome-wide association studies and multi-trait meta-analysis for facial wrinkles using 60K porcine chips. We found that facial wrinkles had high heritability estimates of ~0.7 in Erhualian pigs. Notably, only one genome-wide significant QTL was detected at 34.8 Mb on porcine chromosome 7. The most significant SNP rs80983858 located at the 3255-bp downstream of candidate gene GRM4, and the G allele was of benefit to increase facial wrinkles. Evolutionary and selection analyses suggested that the haplotypes containing G allele were under artificial selection, which was consistent with local animal sacrificial custom praying for longevity. Our findings made important clues for further deciphering the molecular mechanism of swine facial wrinkles formation, and shed light on the research of skin wrinkle development in human or other mammals.
Project description:The organization of the bony face is complex, its morphology being influenced in part by the rest of the cranium. Characterizing the facial morphological variation and craniofacial covariation patterns in extant hominids is fundamental to the understanding of their evolutionary history. Numerous studies on hominid facial shape have proposed hypotheses concerning the relationship between the anterior facial shape, facial block orientation and basicranial flexion. In this study we test these hypotheses in a sample of adult specimens belonging to three extant hominid genera (Homo, Pan and Gorilla). Intraspecific variation and covariation patterns are analyzed using geometric morphometric methods and multivariate statistics, such as partial least squared on three-dimensional landmarks coordinates. Our results indicate significant intraspecific covariation between facial shape, facial block orientation and basicranial flexion. Hominids share similar characteristics in the relationship between anterior facial shape and facial block orientation. Modern humans exhibit a specific pattern in the covariation between anterior facial shape and basicranial flexion. This peculiar feature underscores the role of modern humans' highly-flexed basicranium in the overall integration of the cranium. Furthermore, our results are consistent with the hypothesis of a relationship between the reduction of the value of the cranial base angle and a downward rotation of the facial block in modern humans, and to a lesser extent in chimpanzees.
Project description:Acute ethanol overdose can induce dysfunction of cerebellar motor regulation and cerebellar ataxia. In this study, we investigated the effect of ethanol on facial stimulation-evoked inhibitory synaptic responses in cerebellar Purkinje cells (PCs) in urethane-anesthetized mice, using in vivo patch-clamp recordings. Under voltage-clamp conditions, ethanol (300?mM) decreased the amplitude, half-width, rise time and decay time of facial stimulation-evoked outward currents in PCs. The ethanol-induced inhibition of facial stimulation-evoked outward currents was dose-dependent, with an IC50 of 148.5?mM. Notably, the ethanol-induced inhibition of facial stimulation-evoked outward currents were significantly abrogated by cannabinoid receptor 1 (CB1) antagonists, AM251 and O-2050, as well as by the CB1 agonist WIN55212-2. Moreover, the ethanol-induced inhibition of facial stimulation-evoked outward currents was prevented by cerebellar surface perfusion of the PKA inhibitors H-89 and Rp-cAMP, but not by intracellular administration of the PKA inhibitor PKI. Our present results indicate that ethanol inhibits the facial stimulation-evoked outward currents by activating presynaptic CB1 receptors via the PKA signaling pathway. These findings suggest that ethanol overdose impairs sensory information processing, at least in part, by inhibiting GABA release from molecular layer interneurons onto PCs.
Project description:A central issue in biology concerns the presence, timing and nature of phylotypic periods of development, but whether, when and why species exhibit conserved morphologies remains unresolved. Here, we construct a developmental morphospace to show that amniote faces share a period of reduced shape variance and convergent growth trajectories from prominence formation through fusion, after which phenotypic diversity sharply increases. We predict in silico the phenotypic outcomes of unoccupied morphospaces and experimentally validate in vivo that observed convergence is not due to developmental limits on variation but instead from selection against novel trajectories that result in maladaptive facial clefts. These results illustrate how epigenetic factors such as organismal geometry and shape impact facial morphogenesis and alter the locus of adaptive selection to variation in later developmental events.
Project description:UNLABELLED: In principle, to achieve the most natural and harmonious rejuvenation of the face, all changes that result from the aging process should be corrected. Traditionally, soft tissue lifting and redraping have constituted the cornerstone of most facial rejuvenation procedures. Changes in the facial skeleton that occur with aging and their impact on facial appearance have not been well appreciated. Accordingly, failure to address changes in the skeletal foundation of the face may limit the potential benefit of any rejuvenation procedure. Correction of the skeletal framework is increasingly viewed as the new frontier in facial rejuvenation. It currently is clear that certain areas of the facial skeleton undergo resorption with aging. Areas with a strong predisposition to resorption include the midface skeleton, particularly the maxilla including the pyriform region of the nose, the superomedial and inferolateral aspects of the orbital rim, and the prejowl area of the mandible. These areas resorb in a specific and predictable manner with aging. The resultant deficiencies of the skeletal foundation contribute to the stigmata of the aging face. In patients with a congenitally weak skeletal structure, the skeleton may be the primary cause for the manifestations of premature aging. These areas should be specifically examined in patients undergoing facial rejuvenation and addressed to obtain superior aesthetic results. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Project description:OBJECTIVES:Morphological integration, or the tendency for covariation, is commonly seen in complex traits such as the human face. The effects of growth on shape, or allometry, represent a ubiquitous but poorly understood axis of integration. We address the question of to what extent age and measures of size converge on a single pattern of allometry for human facial shape. METHODS:Our study is based on two large cross-sectional cohorts of children, one from Tanzania and the other from the United States (N?=?7,173). We employ 3D facial imaging and geometric morphometrics to relate facial shape to age and anthropometric measures. RESULTS:The two populations differ significantly in facial shape, but the magnitude of this difference is small relative to the variation within each group. Allometric variation for facial shape is similar in both populations, representing a small but significant proportion of total variation in facial shape. Different measures of size are associated with overlapping but statistically distinct aspects of shape variation. Only half of the size-related variation in facial shape can be explained by the first principal component of four size measures and age while the remainder associates distinctly with individual measures. CONCLUSIONS:Allometric variation in the human face is complex and should not be regarded as a singular effect. This finding has important implications for how size is treated in studies of human facial shape and for the developmental basis for allometric variation more generally.