scholarly journals DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for Non-syndromic Cleft Lip and Palate

2021 ◽  
Vol 9 ◽  
Author(s):  
Juan I. Young ◽  
Susan Slifer ◽  
Jacqueline T. Hecht ◽  
Susan H. Blanton
Keyword(s):  
Dna Methylation ◽  
Candidate Genes ◽  
Dna Sequences ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Differential Methylation ◽  
Potential Contribution ◽  
Hippo Signaling ◽  
Mz Twins

Non-syndromic cleft lip with or without cleft palate (NSCLP) is the most common craniofacial birth defect. The etiology of NSCLP is complex with multiple genes and environmental factors playing causal roles. Although studies have identified numerous genetic markers associated with NSCLP, the role of epigenetic variation remains relatively unexplored. Because of their identical DNA sequences, monozygotic (MZ) twins discordant for NSCLP are an ideal model for examining the potential contribution of DNA methylation to non-syndromic orofacial clefting. In this study, we compared the patterns of whole genome DNA methylation in six MZ twin pairs discordant for NSCLP. Differentially methylated positions (DMPs) and regions (DMRs) were identified in NSCLP candidate genes, including differential methylation in MAFB and ZEB2 in two independent MZ twin pairs. In addition to DNA methylation differences in NSCLP candidate genes, we found common differential methylation in genes belonging to the Hippo signaling pathway, implicating this mechanosensory pathway in the etiology of NSCLP. The results of this novel approach using MZ twins discordant for NSCLP suggests that differential methylation is one mechanism contributing to NSCLP, meriting future studies on the role of DNA methylation in familial and sporadic NSCLP.

scholarly journals Discordant MZ Twins With Cleft Lip and Palate: A Model for Identifying Genes in Complex Traits

2005 ◽  
Vol 8 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Maria Adela Mansilla ◽  
Jane Kimani ◽  
Laura E. Mitchell ◽  
Kaare Christensen ◽  
Dorret I. Boomsma ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Candidate Genes ◽  
Dna Sequences ◽  
Complex Traits ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Somatic Mosaicism ◽  
Interactive Effects ◽  
Sequence Comparisons ◽  
Mz Twins

AbstractMonozygotic (MZ) twins may be discordant for complex traits due to differential environmental exposure in utero, epigenetic variability in imprinting, X chromosome inactivation, or stochastic effects. Occasionally MZ twins may be discordant for chromosomal and single gene disorders due to somatic mosaicism. For complex traits, which are due to the interactive effects of multiple genes and environmental factors, the affected twin of a discordant MZ pair offers the possibility for identifying somatic mutations in candidate genes. DNA sequencing of candidate genes in discordant MZ twins can identify those rare etiologic mutational events responsible for the different phenotypes since the confounding effects of common single nucleotide polymorphisms are eliminated, as DNA sequences should be identical in MZ pairs. In this report we describe the extensive DNA sequencing of 18 candidate genes in a sample of MZ and dizygotic (DZ) twins with nonsyndromic cleft lip with or without cleft palate. We were unable to identify any somatic differences in approximately 34 Kb of DNA sequenced in 13 MZ pairs, for a total of approximately 900 Kb of sequence comparisons, supporting the hypothesis that nonetiologic posttwinning mutations are rare. While no etiologic variants were identified in this study, sequence comparisons of discordant MZ twins can serve as a tool for identifying etiologic mutations in clefting and other complex traits.

scholarly journals Current concepts in genetics of nonsyndromic clefts

2009 ◽  
Vol 42 (01) ◽  
pp. 068-081
Author(s):  
Jyotsna Murthy ◽  
L. V. K. S. Bhaskar
Keyword(s):  
Candidate Genes ◽  
Statistical Power ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Genetic Disorder ◽  
Cell Signalling ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Complex Genetic Disorder

ABSTRACTNonsyndromic cleft lip and palate is a complex genetic disorder with variable phenotype, largely attributed to the interactions of the environment and multiple genes, each potentially having certain effects. Numerous genes have been reported in studies demonstrating associations and/or linkage of the cleft lip and palate phenotypes to alleles of microsatellite markers and single nucleotide polymorphisms within specific genes that regulate transcription factors, growth factors, cell signalling and detoxification metabolisms. Although the studies reporting these observations are compelling, most of them lack statistical power. This review compiles the evidence that supports linkage and associations to the various genetic loci and candidate genes. Whereas significant progress has been made in the field of cleft lip and palate genetics in the past decade, the role of the genes and genetic variations within the numerous candidate genes that have been found to associate with the expression of the orofacial cleft phenotype remain to be determined.

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

Dental Findings in Parents of Children with Cleft Lip and Palate

1996 ◽  
Vol 33 (5) ◽  
pp. 436-439 ◽  
Author(s):  
Peter J. Anderson ◽  
Anthony L.H., Moss
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Normal Population ◽  
Permanent Teeth ◽  
Dental Anomalies ◽  
Facial Skeleton ◽  
Missing Teeth ◽  
Congenitally Missing Teeth ◽  
Congenitally Missing

The incidence of dental abnormalities in the cleft lip and palate population has been reported to be much higher than in the normal population. The role of genes in the production of a cleft lip and palate, and dental anomalies is thought to be complex, with autosomal dominant, recessive, and x-linked genes all playing a role. Noncleft parents can carry some of the cleft lip and palate genes, which produce clinically subtle manifestations in their facial skeleton. The purpose of this study was to look for evidence of increased dental anomalies in the non-cleft parents of cleft lip and palate children. The dentitions of the parents of 60 children with different types of cleft lip and palate were examined prospectively to see whether or not they exhibited features found more readily in the cleft lip and palate rather than did the normal population. Their dentitions were studied to record the following dental features: congenitally missing teeth, supernumerary teeth, or morphologic changes of the crowns of the permanent teeth. The number and position of any frenal attachments were also recorded. The results of this study did not show any differences in incidence of dental anomalies from the noncleft population. There was no evidence to support the hypothesis that congenital absence of lateral incisors is a microform of cleft lip and palate. Further, these results also failed to reveal any consistent pattern in the number and position of frenal attachments.

scholarly journals The important role of MDM2, RPL5, and TP53 in mycophenolic acid-induced cleft lip and palate

Medicine ◽  
2021 ◽  
Vol 100 (21) ◽  
pp. e26101
Author(s):  
Yangyang Lin ◽  
Tao Song ◽  
Elsa M. Ronde ◽  
Gang Ma ◽  
Huiqin Cui ◽  
...  
Keyword(s):  
Mycophenolic Acid ◽  
Cleft Lip ◽  
Cleft Lip And Palate

scholarly journals ROLE OF A PEDODONTIST IN CLEFT LIP AND CLEFT PALATE REHABILITATION - AN OVERVIEW

2021 ◽  
Vol 9 (07) ◽  
pp. 882-906
Author(s):  
Payel Basu ◽  
◽  
Rani Somani ◽  
Deepti Jawa ◽  
Shipra Jaidka ◽  
...  
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Multidisciplinary Care ◽  
Vital Role ◽  
Pediatric Dentist ◽  
Orofacial Region ◽  
The Right ◽  
Potential Area

Cleft lip and palate is one of the most common congenital anomalies requiring multidisciplinary care. Such anomaly is associated with many problems such as impaired feeding, defective speech, hearing difficulties, malocclusion, dental abnormalities, gross facial deformity as well severe psychological problems. Cleft of the lip and palate is one of the complex conditions that occur at a functionally potential area in the orofacial region and also at such a crucial time that strategic interventions at the right age by the concerned specialists becomes the need of the hour. Pediatric dentist is an integral part of the cleft rehabilitative process right from the neonatal period upto the phase of permanent dentition. Being well versed with a childs growth and development, both physical and mental, a Pedodontist helps in restoring function and esthetics in a cleft child, in a most empathetic way. This article describes the enormous challenges faced by these innocent souls and the vital role played by a Pedodontist, to provide comprehensive cleft care, be it preventive, restorative, or interventional care, in order to achieve the best possible outcome and meaningfully improve their quality of life.

The Role of 2D/3D/4D Ultrasound in the Prenatal Assessment of Cleft Lip and Palate

2017 ◽  
pp. 43-59 ◽  
Author(s):  
Pilar Martínez-Ten ◽  
Waldo Sepulveda ◽  
Amy E. Wong ◽  
Gabriele Tonni
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
4D Ultrasound

Role of nostril retainers after rhinoseptoplasties in cleft lip and palate patients

2019 ◽  
Vol 48 ◽  
pp. 14-15
Author(s):  
A.L. Ivanov ◽  
V.A. Pavlovich ◽  
E.I. Reshetnyak ◽  
V.A. Gorbonosov ◽  
D.Y. Anashkina
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate

scholarly journals Bisphenol a Exposure, DNA Methylation, and Asthma in Children

2020 ◽  
Vol 17 (1) ◽  
pp. 298 ◽  
Author(s):  
Chia-Feng Yang ◽  
Wilfried J. J. Karmaus ◽  
Chen-Chang Yang ◽  
Mei-Lien Chen ◽  
I-Jen Wang
Keyword(s):  
Dna Methylation ◽  
Bisphenol A ◽  
Candidate Genes ◽  
Promoter Methylation ◽  
Childhood Asthma ◽  
Methylation Status ◽  
Differential Methylation ◽  
Study Cohort ◽  
Blood Samples ◽  
Asthma In Children

Epidemiological studies have reported the relationship between bisphenol A (BPA) exposure and increased prevalence of asthma, but the mechanisms remain unclear. Here, we investigated whether BPA exposure and DNA methylation related to asthma in children. We collected urinary and blood samples from 228 children (Childhood Environment and Allergic Diseases Study cohort) aged 3 years. Thirty-three candidate genes potentially interacting with BPA exposure were selected from a toxicogenomics database. DNA methylation was measured in 22 blood samples with top-high and bottom-low exposures of BPA. Candidate genes with differential methylation levels were validated by qPCR and promoter associated CpG islands have been investigated. Correlations between the methylation percentage and BPA exposure and asthma were analyzed. According to our findings, MAPK1 showed differential methylation and was further investigated in 228 children. Adjusting for confounders, urinary BPA glucuronide (BPAG) level inversely correlated with MAPK1 promoter methylation (β = −0.539, p = 0.010). For the logistic regression analysis, MAPK1 methylation status was dichotomized into higher methylated and lower methylated groups with cut off continuous variable of median of promoter methylation percentage (50%) while performing the analysis. MAPK1 methylation was lower in children with asthma than in children without asthma (mean ± SD; 69.82 ± 5.88% vs. 79.82 ± 5.56%) (p = 0.001). Mediation analysis suggested that MAPK1 methylation acts as a mediation variable between BPA exposure and asthma. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation.

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