EUROCAT. EUROCAT Website Database. 2017. Available from: http://www.eurocat-network.eu/ACCESSPREVALENCEDATA/PrevalenceTables. [cited 2016 Jan 20].
Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet. 2011;12:167–78.
Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC. Cleft lip and palate. Lancet. 2009;374:1773–85.
Wehby GL, Collett BR, Barron S, Romitti P, Ansley T. Children with oral clefts are at greater risk for persistent low achievement in school than classmates. Arch Dis Child. 2015;100:1148–54.
Sharp GC, Stergiakouli E, Sandy J, Relton C. Epigenetics and orofacial clefts: a brief introduction. Cleft Palate Craniofac J. 2017. doi:10.1597/16-124.
Spritz RA. The genetics and epigenetics of orofacial clefts. Curr Opin Pediatr. 2001;13:556–60.
Plamondon JA, Harris MJ, Mager DL, Gagnier L, Juriloff DM. The clf2 gene has an epigenetic role in the multifactorial etiology of cleft lip and palate in the A/WySn mouse strain. Birth Defects Res A Clin Mol Teratol. 2011;91:716–27.
Juriloff DM, Harris MJ, Mager DL, Gagnier L. Epigenetic mechanism causes Wnt9b deficiency and nonsyndromic cleft lip and palate in the A/WySn mouse strain. Birth Defects Res A Clin Mol Teratol. 2014;100:772–88.
Kuriyama M, Udagawa A, Yoshimoto S, Ichinose M, Sato K, Yamazaki K, et al. DNA methylation changes during cleft palate formation induced by retinoic acid in mice. Cleft Palate Craniofac J. 2008;45:545–51.
Seelan RS, Appana SN, Mukhopadhyay P, Warner DR, Brock GN, Pisano MM, et al. Developmental profiles of the murine palatal methylome. Birth Defects Res A Clin Mol Teratol. 2013;97:171–86.
Seelan RS, Mukhopadhyay P, Pisano MM, Greene RM. Developmental epigenetics of the murine secondary palate. ILAR J. 2012;53:240–52.
Seelan RS, Mukhopadhyay P, Warner DR, Webb CL, Pisano M, Greene RM. Epigenetic regulation of Sox4 during palate development. Epigenomics. 2013;5:131–46.
Fraser FC. The genetics of cleft lip and cleft palate. Am J Hum Genet. 1970;22:336–52.
Harville EW, Wilcox AJ, Lie RT, Vindenes H, Abyholm F. Cleft lip and palate versus cleft lip only: are they distinct defects? Am J Epidemiol. 2005;162:448–53.
Hanny KH, de Vries IAC, Haverkamp SJ, Oomen KPQ, Penris WM, Eijkemans MJC, et al. Late detection of cleft palate. Eur J Pediatr. 2016;175:71–80.
Caramaschi D, Sharp GC, Nohr EA, Berryman K, Lewis SJ, Davey Smith G, et al. Exploring a causal role of DNA methylation in the relationship between maternal vitamin B12 during pregnancy and child’s IQ at age 8, cognitive performance and educational attainment: a two-step Mendelian randomization study. Hum Mol Genet. 2017. doi:10.1093/hmg/ddx164.
Stock NM, Humphries K, Pourcain BS, Bailey M, Persson M, Persson M, et al. Opportunities and challenges in establishing a cohort study: an example from cleft lip/palate research in the United Kingdom. Cleft Palate Craniofac J. 2015;108:49–54.
The Cleft Collective. Available from: www.bristol.ac.uk/dental/cleft-collective/. [cited 2017 Mar 13].
McBride WA, McIntyre GT, Carroll K, Mossey PA. Subphenotyping and classification of orofacial clefts: need for orofacial cleft subphenotyping calls for revised classification. Cleft Palate Craniofac J. 2016;53:539–49.
Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14:R115.
Reese SE, Zhao S, Wu MC, Joubert BR, Parr CL, Håberg SE, et al. DNA methylation score as a biomarker in newborns for sustained maternal smoking during pregnancy. Environ Health Perspect. 2016;125(4):760–6.
Joubert BR, Håberg SE, Nilsen RM, Wang X, Vollset SE, Murphy SK, et al. 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ Health Perspect. 2012;120:1425–31.
Leek JT, Johnson WE, Parker HS, Jaffe AE, Storey JD. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012;28:882–3.
Leek JT, Storey JD. Capturing heterogeneity in gene expression studies by surrogate variable analysis. PLoS Genet. 2007;3:1724–35.
R Core Team, R Development Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2012.
Houseman EA, Accomando WP, Koestler DC, Christensen BC, Marsit CJ, Nelson HH, et al. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics. 2012;13:86.
Reinius LE, Acevedo N, Joerink M, Pershagen G, Dahlén SE, Greco D, et al. Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility. PLoS One. 2012;7(7):e41361.
Min JL, Suderman M, Hemani G. Efficient algorithms for analyzing DNA methylation data: meffil. 2017. https://github.com/perishky/meffil.
Fortin J-P, Labbe A, Lemire M, Zanke BW, Hudson TJ, Fertig EJ, et al. Functional normalization of 450k methylation array data improves replication in large cancer studies. Genome Biol. 2014;15:503.
Pedersen BS, Schwartz DA, Yang IV, Kechris KJ. Comb-p: software for combining, analyzing, grouping and correcting spatially correlated P-values. Bioinformatics. 2012;28:2986–8.
Jaffe AE, Murakami P, Lee H, Leek JT, Fallin MD, Feinberg AP, et al. Bump hunting to identify differentially methylated regions in epigenetic epidemiology studies. Int J Epidemiol. 2012;41:200–9.
Simpkin AJ, Suderman M, Gaunt TR, Lyttleton O, McArdle WL, Ring SM, et al. Longitudinal analysis of DNA methylation associated with birth weight and gestational age. Hum Mol Genet. 2015;24:3752–63.
Acevedo N, Reinius LE, Vitezic M, Fortino V, Söderhäll C, Honkanen H, et al. Age-associated DNA methylation changes in immune genes, histone modifiers and chromatin remodeling factors within 5 years after birth in human blood leukocytes. Clin Epigenetics BioMed Central. 2015;7:34.
Bohlin J, Håberg SE, Magnus P, Reese SE, Gjessing HK, Magnus MC, et al. Prediction of gestational age based on genome-wide differentially methylated regions. Genome Biol. 2016;17:207.
Phipson B, Maksimovic J, Oshlack A. missMethyl: an R package for analyzing data from Illumina’s HumanMethylation450 platform. Bioinformatics. 2016;32:286–8.
Piñero J, Bravo À, Queralt-Rosinach N, Gutiérrez-Sacristán A, Deu-Pons J, Centeno E, et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. 2017;45:D833–9. Oxford University Press.
Funato N, Nakamura M. Identification of shared and unique gene families associated with oral clefts. Int J Oral Sci. 2017. doi:10.1038/ijos.2016.56.
Smyth GK. Limma: linear models for microarray data. In: Gentleman R, Carey VSD, Irizarry W, editors. Bioinforma. Comput. Biol. Solut. using R Bioconductor. New York: Springer; 2005. p. 397–420.
Sen A, Heredia N, Senut M-C, Land S, Hollocher K, Lu X, et al. Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren. Sci Rep. 2015;5:14466.
Gao S, Li X, Amendt BA. Understanding the role of Tbx1 as a candidate gene for 22q11.2 deletion syndrome. Curr Allergy Asthma Rep. 2013;13:613–21.
Paranaíba L-M-R, de Aquino S-N, Bufalino A, Martelli-Júnior H, Graner E, Brito L-A, et al. Contribution of polymorphisms in genes associated with craniofacial development to the risk of nonsyndromic cleft lip and/or palate in the Brazilian population. Med Oral Patol Oral Cir Bucal. 2013;18:e414–20.
Funato N, Nakamura M, Richardson JA, Srivastava D, Yanagisawa H. Tbx1 regulates oral epithelial adhesion and palatal development. Hum Mol Genet. 2012;21:2524–37. Oxford University Press.
Chung KS, Park HH, Ting K, Takita H, Apte SS, Kuboki Y, et al. Modulated expression of type X collagen in the Meckel’s cartilage with different developmental fates. Dev Biol. 1995;170:387–96.
Nikopensius T, Jagomägi T, Krjutškov K, Tammekivi V, Saag M, Prane I, et al. Genetic variants in COL2A1, COL11A2, and IRF6 contribute risk to nonsyndromic cleft palate. Birth Defects Res Part A Clin Mol Teratol. 2010;88:748–56. Wiley Subscription Services, Inc., A Wiley Company.
Melkoniemi M, Koillinen H, Männikkö M, Warman ML, Pihlajamaa T, Kääriäinen H, et al. Collagen XI sequence variations in nonsyndromic cleft palate, Robin sequence and micrognathia. Eur J Hum Genet. 2003;11:265–70.
Yu H, Smallwood PM, Wang Y, Vidaltamayo R, Reed R, Nathans J. Frizzled 1 and frizzled 2 genes function in palate, ventricular septum and neural tube closure: general implications for tissue fusion processes. Dev Co Biologists. 2010;137:3707–17.
Beaty TH, Hetmanski JB, Fallin MD, Park JW, Sull JW, McIntosh I, et al. Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations. Hum Genet. 2006;120:501–18.
Jugessur A, Shi M, Gjessing HK, Lie RT, Wilcox AJ, Weinberg CR, et al. Fetal genetic risk of isolated cleft lip only versus isolated cleft lip and palate: a subphenotype analysis using two population-based studies of orofacial clefts in scandinavia. Birth Defects Res Part A Clin Mol Teratol. 2011;91:85–92.
Ludwig KU, Böhmer AC, Bowes J, Nikolić M, Ishorst N, Wyatt N, et al. Imputation of orofacial clefting data identifies novel risk loci and sheds light on the genetic background of cleft lip ± cleft palate and cleft palate only. Hum Mol Genet. 2017;26(4):829–42.
Radhakrishna U. Small players with a big role: microRNAs in pathophysiology of cleft lip and palate. Indian J Hum Genet. 2012;18:272–3. Medknow Publications.
Li J, Zou J, Li Q, Chen L, Gao Y, Yan H, et al. Assessment of differentially expressed plasma microRNAs in nonsyndromic cleft palate and nonsyndromic cleft lip with cleft palate. Oncotarget. 2016;7:86266–79.
Kee N, Wilson N, De Vries M, Bradford D, Key B, Cooper HM. Neogenin and RGMa control neural tube closure and neuroepithelial morphology by regulating cell polarity. J Neurosci. 2008;28:12643–53.
Itoh K, Ossipova O, Sokol SY. GEF-H1 functions in apical constriction and cell intercalations and is essential for vertebrate neural tube closure. J Cell Sci. 2014;127:2542–53.
Taniguchi K, Anderson AE, Melhuish TA, Carlton AL, Manukyan A, Sutherland AE, et al. Genetic and molecular analyses indicate independent effects of TGIFs on nodal and Gli3 in neural tube patterning. Eur J Hum Genet. 2017;25:208–15.
Lu Z-Y, Morales M, Khartulyari S, Mei M, Murphy KM, Stanislawska-Sachadyn A, et al. Genetic and biochemical determinants of serum concentrations of monocyte chemoattractant protein-1, a potential neural tube defect risk factor. Birth Defects Res Part A Clin Mol Teratol. 2008;82:736–41.
Joosten PHLJ, Toepoel M, Mariman ECM, Van Zoelen EJJ. Promoter haplotype combinations of the platelet-derived growth factor alpha-receptor gene predispose to human neural tube defects. Nat Genet. 2001;27:215–7.
Opitz JM, Gilbert EF. CNS anomalies and the midline as a ‘developmental field’. Am J Med Genet. 1982;12:443–55.
Czeizel. Schisis-association. Am J Med Genet. 1981;10:25–35.
Greene NDE, Copp AJ. Neural tube defects. Annu Rev Neurosci. 2014;37:221–42.
Copp AJ, Stanier P, Greene NDE. Neural tube defects: recent advances, unsolved questions, and controversies. Lancet Neurol. 2013;12:799–810.
Kousa YA, Mansour TA, Seada H, Matoo S, Schutte BC. Shared molecular networks in orofacial and neural tube development. Birth Defects Res Part A Clin Mol Teratol. 2016;109(2):169–79.
Dick KJ, Nelson CP, Tsaprouni L, Sandling JK, Aïssi D, Wahl S, et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet. 2014;383:1990–8.
Richmond RC, Sharp GC, Ward ME, Fraser A, Lyttleton O, McArdle WL, et al. DNA methylation and BMI: investigating identified methylation sites at HIF3A in a causal framework. Diabetes. 2016;65:1231–44.
Joubert BR, den Dekker HT, Felix JF, Bohlin J, Ligthart S, Beckett E, et al. Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns. Nat Commun. 2016;7:10577.
Lee H, Jaffe AE, Feinberg JI, Tryggvadottir R, Brown S, Montano C, et al. DNA methylation shows genome-wide association of NFIX, RAPGEF2 and MSRB3 with gestational age at birth. Int J Epidemiol. 2012;41:188–99.
Jakobsen LP, Borup R, Vestergaard J, Larsen LA, Lage K, Maroun LL, et al. Expression analyses of human cleft palate tissue suggest a role for osteopontin and immune related factors in palatal development. Exp Mol Med. 2009;41:77. Nature Publishing Group.
Walker RF, Liu JS, Peters BA, Ritz BR, Wu T, Ophoff RA, et al. Epigenetic age analysis of children who seem to evade aging. Aging. 2015;7:334–9.
Simpkin AJ, Hemani G, Suderman M, Gaunt TR, Lyttleton O, McArdle WL, et al. Prenatal and early life influences on epigenetic age in children: a study of mother-offspring pairs from two cohort studies. Hum Mol Genet. 2015;25:191–201.
Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23:R89–98.
Davey Smith G, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:1–22.
Barrow JR, Capecchi MR. Compensatory defects associated with mutations in Hoxa1 restore normal palatogenesis to Hoxa2 mutants. Development. 1999;126:5011–26.
Gendron-Maguire M, Mallo M, Zhang M, Gridley T. Hoxa-2 mutant mice exhibit homeotic transformation of skeletal elements derived from cranial neural crest. Cell. 1993;75:1317–31.
Letra A, Menezes R, Govil M, Fonseca RF, McHenry T, Granjeiro JM, et al. Follow-up association studies of chromosome region 9q and nonsyndromic cleft lip/palate. Am J Med Genet Part A. 2010;152A:1701–10.
Rattanasopha S, Tongkobpetch S, Srichomthong C, Siriwan P, Suphapeetiporn K, Shotelersuk V. PDGFRa mutations in humans with isolated cleft palate. Eur J Hum Genet. 2012;20:1058–62.
Letra A, Menezes R, Cooper ME, Fonseca RF, Tropp S, Govil M, et al. CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate. Cleft Palate Craniofac J. 2011;48:363–70. Allen Press Publishing Services.
Rainger J, van Beusekom E, Ramsay JK, McKie L, Al-Gazali L, Pallotta R, et al. Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice. PLoS Genet. 2011;7:e1002114.
Avila JR, Jezewski PA, Vieira AR, Orioli IM, Castilla EE, Christensen K, et al. PVRL1 variants contribute to non-syndromic cleft lip and palate in multiple populations. Am J Med Genet A. 2006;140:2562–70.
Machida J, Félix TM, Murray JC, Yoshiura K, Tanemura M, Kamamoto M, et al. Searching for genes for cleft lip and/or palate based on breakpoint analysis of a balanced translocation t(9;17)(q32;q12). Cleft Palate-Craniofacial J. 2009;46:532–40.