Am. Hoyme, H. E., Kalberg, W. O., Elliott, A. J., Blankenship, J., Buckley, D., Marais, A. S., et al. Res. Furthermore, it is unclear whether the epigenetic profile of lip and palate tissues postnatally are comparable to the same tissues during embryonic development. doi: 10.1136/bmjopen-2013-002910, Djordjevic, J., Zhurov, A. I., and Richmond, S. (2016). Behav. Epigenetic processes include DNA methylation, histone modification and chromatin remodeling, which can affect gene expression by regulating transcription (Jaenisch and Bird, 2003; Bird, 2007; Gibney and Nolan, 2010; Allis and Jenuwein, 2016). JAMA Pediatr. Genet. 371:20150380. doi: 10.1098/rstb.2015.0380, Hennessy, R. J., Baldwin, P. A., Browne, D. J., Kinsella, A., and Waddington, J. L. (2010). (2014). J. Epidemiol. Proc. (2015). doi: 10.1371/journal.pone.0118355, Paternoster, L., Zhurov, A. I., Toma, A. M., Kemp, J. P., Pourcain, B. S., Timpson, N. J., et al. (2016). (2016). (2014). J. Craniomaxillofac. (2011). Three-dimensional assessment of functional change following Class 3 orthognathic correctiona preliminary report. doi: 10.1534/genetics.116.193185, Cousminer, D. L., Berry, D. J, Timpson, N. J., Ang, W., Thiering, E., Byrne, E. M., et al. The fusion between the facial processes depends on a series of events involving cell migration, growth, adhesion, differentiation and apoptosis. For detailed information on the biological basis of individual genes, the reader should refer to the original articles. (2013). Rep. 7:10444. doi: 10.1038/s41598-017-10752-w. Hammond, N. L., Dixon, J., and Dixon, M. J. While the R in Scottish is hardly spoken like there are two Rs, the TH in Irish, on the other hand, sounds like a soft T. Different facial measures have been applied to facial images obtained from a variety of acquisition systems (2D and 3D). A number of Scottish people have a wavy texture to their hair. Sci. Although, it is known that the PAX3 influences the prominence of the bridge of the nose it is more challenging to know to what extent this influences adjacent facial regions in each individual. Mol. The influence of snoring, mouth breathing and apnoea on facial morphology in late childhood: a three-dimensional study. There was reduced facial convexity (SNAI1), obtuse nasolabial angles, more protrusive chins (SNAI1, IRF6, MSX1, MAFB), increased lower facial heights (SNAI1), thinner and more retrusive lips and more protrusive foreheads (ABCA4-ARHGAP29, MAFB) in the nsCL/P relatives compared to controls. The term Gaelic, as a language, applies only to the language of Scotland. Given that their DNA is so close that as of October 2013 it was not yet determined which of Celt or Saxon the House of Oldenburg (Mountbatten) is, A. Illustrated review of the embryology and development of the facial region, part 1: early face and lateral nasal cavities. Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965. Eur. Rep. 5:17788. doi: 10.1038/srep17788, Xuan, Z., Zhongpeng, Y., Yanjun, G., Jiaqi, D., Yuchi, Z., Bing, S., et al. doi: 10.1002/humu.22054, Heike, C. L., Upson, K., Stuhaug, E., and Weinberg, S. M. (2010). B., Manyama, M., Kimwaga, E., Mathayo, J., Larson, J. R., Liberton, D. K., et al. Disruption in early embryological development can lead to wide-ranging effects from subtle neurologic and facial features, which includes asymmetry, to significant impact on facial shape as characterized by a CL/P or in anomalies observed in craniofacial syndromes. Childbirth 14:127. doi: 10.1186/1471-2393-14-127, Le, T. T., Farkas, L. G., Ngim, R. C., Levin, L. S., and Forrest, C. R. (2002). Am. Eur. The timing, vectors and duration of surges in facial growth tend to be different for males and females and between populations contributing to overall facial variation (Kau et al., 2010; Hopman et al., 2014; Richmond R.C. Genetic and facial phenotype data can be used to improve understanding of human history. doi: 10.1136/adc.41.220.613. Genome-wide association study of facial morphology reveals novel associations with FREM1 and PARK2. 40, 3642. WebDiscover the Northern Irish accent. The Irish temperament is world-famous. Curr. (2003). 18, 3348. Development 126, 48734884. Peter Forsberg (hockey player) (Notice how his eyes are higher up. Int. Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders. 80, 359369. Behav. The gene regulatory systems are complex and numerous and detailing these regulatory mechanisms has been the goal of the NIH Roadmap Epigenomics Project whereby next generation sequencing technologies (e.g., ChiP seq) are employed to map DNA methylation, histone modifications, chromatin accessibility in a variety of research media such as, animal models (mouse, chicken, zebrafish, frog, and primates) and stem cells and regulated human fetal tissues (Hochheiser et al., 2011; Roosenboom et al., 2016; Van Otterloo et al., 2016). Birth Defects Res. (2016). doi: 10.1097/01.scs.0000171847.58031.9e, Farkas, L. G., Tompson, B. D., Katic, M. J., and Forrest, C. R. (2002). 115, 299320. However, large-scale population studies are needed to identify more genetic variants not only in the context of facial shape but general body development with particularly attention to puberty. 9:63. doi: 10.1186/s13148-017-0362-2, Shi, M., Wehby, G. L., and Murray, J. C. (2008). MSc thesis, Cardiff University, Cardiff. doi: 10.1016/S0889-5406(94)70038-9, Popat, H., Richmond, S., and Drage, N. A. (2017). Pharmacol. DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis. doi: 10.1073/pnas.0914628107. Arch. Population cohort studies enables researchers to study the environmental, disease and metabolic risk factors and genetic interactions from pre-birth throughout the lifecourse. Traditionally yes they were certainly different in appearance - but there has been so much intermingling the differences have become very blurred. Differences in relative size, shape and spatial arrangement (vertical, horizontal and depth) between the various facial features (e.g., eyes, nose, lips etc.) What are Typical Irish Facial Features? Genet. Genetics 205, 967978. (2018). Department of Human Genetics, Faculty of Medicine, KU Leuven, Belgium, Children's Hospital of Philadelphia, United States. Ideally facial images should be captured at birth, 5, 9, 12, 15, and 18 years of age and repeated every 10 years of age to capture facial features. Impressions of an individuals health are integral to social interactions and judgments are made on the visual appearance of skin, degree of roundness of the face and facial expression (Henderson et al., 2016). 12:e1006149. Orienting the causal relationship between imprecisely measured traits using GWAS summary data. on the growth of the face, for example, remodeling of the facial skeleton, spatial changes of the constituent parts of the facial skeleton through sutures, condylar and nasal cartilages as well as the soft tissues, neural and vascular networks. Large-scale objective phenotyping of 3D facial morphology. doi: 10.1007/s00439-016-1754-7, Lippert, C., Sabatini, R., Maher, M. C., Kang, E. Y., Lee, S., Arikan, O., et al. There are many imaging systems available to capture the external facial surface topography such as photography, lasers, photogrammetry, magnetic resonance Imaging (MRI), computerized tomography (CT), and cone beam computerized tomography (CBCT). Orthod. In a female, the width is roughly the same proportion, but the foot is just longer than the face is high, and the hand is at most 3/4 of the same height. J. Epidemiol. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Pediatrics 138:e20154256. Over the last 6 years there has been significant progress with 9 published GWAS which have identified over 50 loci associated with facial traits (Liu et al., 2012; Paternoster et al., 2012; Adhikari et al., 2016; Cole et al., 2016; Shaffer et al., 2016; Lee et al., 2017; Cha et al., 2018; Claes et al., 2018; Crouch et al., 2018). doi: 10.1038/ejhg.2013.289, Howe, L. J., Lee, M. K., Sharp, G. C., Smith, G. D., St Pourcain, B., Shaffer, J. R., et al. Epigenomics 10, 2742. Confirming genes influencing risk to cleft lip with/without cleft palate in a case-parent trio study. Acad. Another mechanism via which environmental influences can affect facial traits is natural selection, where certain facial traits may have beneficial effects on reproductive fitness. Nat. Front. A systematic review and meta-analyses. Homo 61, 191203. The HIrisPlex-S system for eye, hair and skin colour prediction from DNA: introduction and forensic developmental validation. Morphometrics, 3D imaging, and craniofacial development. Z., Segurel, L., Tung, J. Y., and Hinds, D. A. They both use potatoes, oats, barley, dairy products, lamb, bacon, herring, salmon, scallops, and beef. Nat. The first wave of genetic studies of craniofacial Mendelian traits were based on linkage or candidate gene studies of genetic loci known to be involved in craniofacial development or genetic syndromes affecting the face. Psychol. Nat. 22, 38073817. There is the potential for relationships between medical and facial conditions to be explored using genetic summary data. PLoS Genet. A., Mattern, B. C., Claes, P., McEcoy, B., Hughes, C., and Shriver, M. D. (2017). Lancet Oncol. The US cancer moonshot initiative. (2016). The availability of summary statistics on large GWAS studies will also enable the application of quantitative genetics methods to further investigate the genetic architecture of facial morphology. Scottish is the term referred to peoples who live in Scotland, whereas Irish is the term that is referred to peoples who live in Ireland. 7:10815. doi: 10.1038/ncomms10815, PubMed Abstract | CrossRef Full Text | Google Scholar, Aelion, C. M., Airhihenbuwa, C. O., Alemagno, S., Amler, R. W., Arnett, D. K., Balas, A., et al. DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood. Estimating the sex-specific effects of genes on facial attractiveness and sexual dimorphism. The modifiable nature of epigenetic processes has led to much excitement that these processes may mediate the effect of environmental exposures. (2007). Oral Maxillofac. Similarly, epigenetic processes may mediate the effects of germline genetic variation. 355, 175182. Forensic Sci. Reported shared influences of medical conditions, normal facial variation with associated genes. 1), 101116. Genet. DNA methylation mediates genetic liability to non-syndromic cleft lip/palate. doi: 10.1002/ajpa.20424. 18, 549555. Orthod. A., Guerin, D. J., Litzky, J. F., Chavan, N. R., et al. 268, 3944. doi: 10.1002/rcs.352, Bhatia, S. N., Wright, G. W., and Leighton, B. C. (1979). Front. Plast. Genet. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. (2010). B., Manyama, M., Larson, J. R., Liberton, D. K., Ferrara, T. M., Riccardi, S. L., et al. While each person is unique, people of Scottish descent are generally average or tall in stature and have a thin build. doi: 10.1097/00001665-200403000-00027, Farkas, L. G., Katic, M. J., and Forrest, C. R. (2005). Rev. Acad. Couldn't necessarily say what exactly it is but yeah, but not Genet. Sci. Many of the previously discussed genetic variants associated with facial traits in GWAS reside in non-protein coding regions of the genome with unclear functional relevance. Fine tuning of craniofacial morphology by distant-acting enhancers. Roosenboom, J., Hens, G., Mattern, B. C., Shriver, M. D., and Claes, P. (2016). (1996). Detection and interpretation of shared genetic influences on 42 human traits. Heritability of mandibular cephalometric variables in twins with completed craniofacial growth. AJNR Am. Genet. doi: 10.2174/157015907781695955, Wilde, S., Timpson, A., Kirsanow, K., Kaiser, E., Kayser, M., Unterlnder, M., et al. GWAS may be underestimating and twin and family studies overestimating the levels of heritability. Embryonic features that contribute to facial development. The role of enhancers modifying histones, chromatin states are key for normal range craniofacial development and relative position of the various craniofacial tissues. Your dinner is not Craniofacial epigenetic studies to date have largely focused on orofacial clefts. Surgical procedures are not always simple as often in CL/P patients there is often insufficient tissues available (epidermis/dermis, cartilage and bone with disrupted orientation of muscle fibers). There are words each language use for their own, like wee for the Scottish and aye for the Irish. Dentofacial Orthop. These landmarks are defined by identifiable/describable facial features, e.g., nasion, inner/outer canthi, commissures that can generate Euclidean distances, angles, and ratios (Farkas et al., 2002, 2004, 2005). 2, 179187. Genet. Int. This approach may be appropriate for unique facial characteristics but is more challenging when one or more genes are associated with the variation of facial phenotype (e.g., prominence of the nasal bridge or length of the nose, hair and eye color/tones). There are many published norms for different racial/population groups used to identify individuals who fall within the normal range and identify any facial dysmorphologies. The Ceili Dances consist of quadrilles, reels, jigs and long or round dances. (2014). (2012). Keywords: 3D imaging, admixture, ancestry, facial variation, geometric morphometrics, facial genetics, facial phenotyping, genetic-environmental influences, Citation: Richmond S, Howe LJ, Lewis S, Stergiakouli E and Zhurov A (2018) Facial Genetics: A Brief Overview. The authors would like to thank Dr. Ryan Arathimos (University of Bristol) for advice on a draft of the manuscript. Age prediction using methylation techniques have indicated a mean absolute deviation of 58 years (Xu et al., 2015; Bocklandt et al., 2011; Hamano et al., 2017). These were the most native Irish traditional folk dances. Behav. Am. J. Orthod. 9:e1003375. U.S.A. 115, E676E685. et al., 2015) and Mendelian randomization can provide information on the genetic overlap of facial phenotypes with other genetic traits and the possibility to causally assess the association of risk factors with face development (Smith and Ebrahim, 2003). (2012). In addition, anthropometric masks have been proposed whereby five landmarks are used to crudely orientate the 3D facial shells which are then non-rigidly mapped on to a template which generates about 10,000 quasi landmarks (Claes et al., 2012). J. Hum. A population-based cross-sectional study of the association between facial morphology and cardiometabolic risk factors in adolescence. Parsons, T. E., Downey, C. M., Jirik, F. R., Hallgrimsson, B., and Jamniczky, H. A. PLoS One 11:e0162250. Hum. Genetic interactions or epistasis may also explain the low levels of variance recorded. Normal facial development is dependent on Cranial Neural Crest Cells and correctly spatially positioned and differentiated tissues and structures that influence the shape and morphological features of the face. Oral Pathol. (2016). Dev. For the Scottish, they have Prince Charlie and the Argyle designs. Nature 447:425. doi: 10.1038/nature05918, Relton, C. L., and Davey Smith, G. (2012). Ashique, A. M., Fu, K., and Richman, J. M. (2002). doi: 10.1016/S1470-2045(16)30054-7, Al Ali, A., Richmond, S., Popat, H., Playle, R., Pickles, T., Zhurov, A. I., et al. Genet. Robot 6, 422430. Dev. (2003). Comput. To quantify facial features, landmarks have been traditionally used, taken either directly from the face or derived from photographs or radiographs. Association between prenatal alcohol exposure and craniofacial shape of children at 12 Months of Age. doi: 10.1034/j.1600-0544.2001.040303.x, Carson, E. A. In addition, genetic and environmental factors will have subtle influences on the face. J. Epidemiol. Nature 461, 199205. doi: 10.1038/nature08451, Visscher, P. M., Hill, W. G., and Wray, N. R. (2008). Dentofacial Orthop. J. Med. The growing number of GWAS datasets has allowed exploration of the shared genetic influences on different phenotypes (Bulik-Sullivan B. et al., 2015; Pickrell et al., 2016). Previously published studies that have identified gene-phenotype associations which provides evidence of associations for complex facial traits which can be integrated into prediction models. doi: 10.1073/pnas.1711125114, Little, A. C., Burt, D. M., Penton-Voak, I. S., and Perrett, D. I. Face height (28.8%), width of the eyes (10.4%) and prominence of the nose (6.7%) explained 46% of total facial variance (Toma et al., 2012). doi: 10.1016/j.fsigen.2015.02.003, Keating, B., Bansal, A. T., Walsh, S., Millman, J., Newman, J., Kidd, K., et al. The teeth and faces of twins: providing insights into dentofacial development and oral health for practising oral health professionals. I notice that many folks from the South and Lower Midwest (especially Kentucky, Indiana and Tennessee), where Irish and Scottish ancestry are the most But light eyes and freckles are much more common. The long-term impact of folic acid in pregnancy on offspring DNA methylation: follow-up of the Aberdeen Folic Acid Supplementation Trial (AFAST). 234, 103110. J. Hum. doi: 10.1038/414909a, Leslie, E. J., Carlson, J. C., Shaffer, J. R., Butali, A., Bux, C. J., Castilla, E. E., et al. doi: 10.1093/hmg/ddt104, Cousminer, D. L., Stergiakouli, E., Berry, D. J., Ang, W., Groen-Blokhuis, M. M., Krner, A., et al. Noggin and retinoic acid transform the identity of avian facial prominences. Evol. Heavy metals and placental fetal-maternal barrier: a mini-review on the major concerns. The handling Editor is currently collaborating with author SR and confirms the absence of any other collaboration. J. Hum. Copyright 2018 Richmond, Howe, Lewis, Stergiakouli and Zhurov. doi: 10.1002/ajmg.a.31760. Exploratory genotype-phenotype correlations of facial form and asymmetry in unaffected relatives of children with non-syndromic cleft lip and/or palate. (2015). Generally, most modifiable environmental factors have only subtle effects on the face. doi: 10.1371/journal.pgen.1004724, Hallgrimsson, B., Percival, C. J., Green, R., Young, N. M., Mio, W., and Marcucio, R. (2015). Development 143, 26772688. A genetic atlas of human admixture history. Use of 3-dimensional surface acquisition to study facial morphology in 5 populations. genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. There are words each language use for their own, like wee for the Scottish and aye for the Irish. Sci. Proportionality in Asian and North American Caucasian faces using neoclassical facial canons as criteria. Commun. Curr. Head Face Med. Rep. 7:2441. doi: 10.1038/s41598-017-02721-0. Medical Image Understanding and Analysis. Maternal smoking during pregnancy is associated with mitochondrial DNA methylation. Who is the most beautiful woman in Ireland? Epigenetics refers to mitotically (and perhaps, controversially meiotically) heritable changes in gene expression which are not explained by changes to the DNA base-pair sequence. doi: 10.1097/MJT.0b013e3182583bd1, Jablonski, N. G., and Chaplin, G. (2000). TABLE 1. A spatially-dense regression study of facial form and tissue depth: towards an interactive tool for craniofacial reconstruction. doi: 10.1093/ejo/cjv062, Smith, G. D., and Ebrahim, S. (2003). Indeed, there is evidence to suggest that high levels of prenatal alcohol exposure can influence facial morphology; individuals with fetal alcohol syndrome disorders can present with facial abnormalities (Hoyme et al., 2016) as well as other developmental anomalies such as caudate nucleus asymmetry and reduced mass of the brain (Suttie et al., 2018).
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