A genome-wide scan for loci predisposing to non-syndromic cleft lip with or without cleft palate in two large Syrian families

2003 ◽  
Vol 123A (2) ◽  
pp. 140-147 ◽  
Author(s):  
Diego F. Wyszynski ◽  
Hasan Albacha-Hejazi ◽  
Mohammed Aldirani ◽  
Moustafa Hammod ◽  
Hikmat Shkair ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Scan

scholarly journals Erratum: A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4

2010 ◽  
Vol 42 (8) ◽  
pp. 727-727 ◽  
Author(s):  
Terri H Beaty ◽  
Jeffrey C Murray ◽  
Mary L Marazita ◽  
Ronald G Munger ◽  
Ingo Ruczinski Jacqueline B Hetmanski ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Association Study ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Risk Variants ◽  
Genome Wide ◽  
A Genome

scholarly journals Identification of Copy Number Variation Among Nonsyndromic Cleft Lip and or Without Cleft Palate With Hypodontia: A Genome-Wide Association Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Norliana Ghazali ◽  
Normastura Abd Rahman ◽  
Azlina Ahmad ◽  
Sarina Sulong ◽  
Thirumulu Ponnuraj Kannan
Keyword(s):  
Copy Number Variation ◽  
Cleft Palate ◽  
Copy Number ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Quantitative Polymerase Chain Reaction ◽  
Copy Number Variations ◽  
Genome Wide ◽  
A Genome ◽  
Number Variation

Nonsyndromic cleft lip and or without cleft palate (NSCL/P) with the hypodontia is a common developmental abnormality in humans and animals. This study identified the genetic aberration involved in both NSCL/P and hypodontia pathogenesis. A cross-sectional study using genome-wide study copy number variation-targeted CytoScan 750K array carried out on salivary samples from 61 NSCL/P and 20 noncleft with and without hypodontia Malay subjects aged 7–13 years old. Copy number variations (CNVs) of SKI and fragile histidine triad (FHIT) were identified in NSCL/P and noncleft children using quantitative polymerase chain reaction (qPCR) as a validation analysis. Copy number calculated (CNC) for each gene determined with Applied Biosystems CopyCaller Software v2.0. The six significant CNVs included gains (12q14.3, 15q26.3, 1p36.32, and 1p36.33) and losses (3p14.2 and 4q13.2) in NSCL/P with hypodontia patients compared with the NSCL/P only. The genes located in these regions encoded LEMD3, IGF1R, TP73, SKI, FHIT, and UGT2β15. There were a significant gain and loss of both SKI and FHIT copy number in NSCL/P with hypodontia compared with the noncleft group (p < 0.05). The results supported that CNVs significantly furnish to the development of NSCL/P with hypodontia.

scholarly journals Genome-Wide Scan for Parent-of-Origin Effects in a sub-Saharan African Cohort With Nonsyndromic Cleft Lip and/or Cleft Palate (CL/P)

2021 ◽  
pp. 105566562110363
Author(s):  
Lord J. J. Gowans ◽  
Carissa L. Comnick ◽  
Peter A. Mossey ◽  
Mekonen A. Eshete ◽  
Wasiu L. Adeyemo ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Association Studies ◽  
African Ancestry ◽  
Parental Origin ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
A Genome ◽  
Parent Of Origin ◽  
Origin Effects

Objective Nonsyndromic cleft lip and/or cleft palate (NSCL/P) have multifactorial etiology where genetic factors, gene–environment interactions, stochastic factors, gene–gene interactions, and parent-of-origin effects (POEs) play cardinal roles. POEs arise when the parental origin of alleles differentially impacts the phenotype of the offspring. The aim of this study was to identify POEs that can increase risk for NSCL/P in humans using a genome-wide dataset. Methods The samples (174 case-parent trios from Ghana, Ethiopia, and Nigeria) included in this study were from the African only genome wide association studies (GWAS) that was published in 2019. Genotyping of individual DNA using over 2 million multiethnic and African ancestry-specific single-nucleotide polymorphisms from the Illumina Multi-Ethnic Genotyping Array v2 15070954 A2 (genome build GRCh37/hg19) was done at the Center for Inherited Diseases Research. After quality control checks, PLINK was employed to carry out POE analysis employing the pooled subphenotypes of NSCL/P. Results We observed possible hints of POEs at a cluster of genes at a 1 mega base pair window at the major histocompatibility complex class 1 locus on chromosome 6, as well as at other loci encompassing candidate genes such as ASB18, ANKEF1, AGAP1, GABRD, HHAT, CCT7, DNMT3A, EPHA7, FOXO3, lncRNAs, microRNA, antisense RNAs, ZNRD1, ZFAT, and ZBTB16. Conclusion Findings from our study suggest that some loci may increase the risk for NSCL/P through POEs. Additional studies are required to confirm these suggestive loci in NSCL/P etiology.

scholarly journals Non-Syndromic Cleft Lip with or without Cleft Palate: Genome-Wide Association Study in Europeans Identifies a Suggestive Risk Locus at 16p12.1 and Supports SH3PXD2A as a Clefting Susceptibility Gene

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1023 ◽  
Author(s):  
Iris ALM van Rooij ◽  
Kerstin U Ludwig ◽  
Julia Welzenbach ◽  
Nina Ishorst ◽  
Michelle Thonissen ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Association Study ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Small Sample ◽  
Genome Wide Association ◽  
P Value ◽  
Genome Wide ◽  
A Genome

Non-syndromic cleft lip with or without cleft palate (nsCL/P) ranks among the most common human congenital malformations, and has a multifactorial background in which both exogenous and genetic risk factors act in concert. The present report describes a genome-wide association study (GWAS) involving a total of 285 nsCL/P patients and 1212 controls from the Netherlands and Belgium. Twenty of the 40 previously reported nsC/LP susceptibility loci were replicated, which underlined the validity of this sample. SNV-based analysis of the data identified an as yet unreported suggestive locus at chromosome 16p12.1 (p-value of the lead SNV: 4.17 × 10−7). This association was replicated in two of three patient/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized SH3PXD2A at chromosome 10q24.33 as a candidate gene for nsCL/P. To date, support for this gene as a cleft gene has been restricted to data from zebrafish and a knockout mouse model. The present GWAS was the first to implicate SH3PXD2A in non-syndromic cleft formation in humans. In summary, although performed in a relatively small sample, the present GWAS generated novel insights into nsCL/P etiology.

scholarly journals A genome-wide linkage scan for cleft lip and cleft palate identifies a novel locus on 8p11-23

2007 ◽  
Vol 143A (8) ◽  
pp. 846-852 ◽  
Author(s):  
B.M. Riley ◽  
R.E. Schultz ◽  
M.E. Cooper ◽  
T. Goldstein-McHenry ◽  
S. Daack-Hirsch ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Genome Wide ◽  
A Genome

A Genome-Wide Association Study Identifies a Locus for Nonsyndromic Cleft Lip with or without Cleft Palate on 8q24

2009 ◽  
Vol 155 (6) ◽  
pp. 909-913 ◽  
Author(s):  
Struan F.A. Grant ◽  
Kai Wang ◽  
Haitao Zhang ◽  
Wendy Glaberson ◽  
Kiran Annaiah ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Association Study ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4

2010 ◽  
Vol 42 (6) ◽  
pp. 525-529 ◽  
Author(s):  
Terri H Beaty ◽  
Jeffrey C Murray ◽  
Mary L Marazita ◽  
Ronald G Munger ◽  
Ingo Ruczinski ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Association Study ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Risk Variants ◽  
Genome Wide ◽  
A Genome

scholarly journals A genome-wide scan of cleft lip triads identifies parent-of-origin interaction effects between ANK3 and maternal smoking, and between ARHGEF10 and alcohol consumption

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 960 ◽  
Author(s):  
Øystein Ariansen Haaland ◽  
Julia Romanowska ◽  
Miriam Gjerdevik ◽  
Rolv Terje Lie ◽  
Håkon Kristian Gjessing ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Environmental Exposures ◽  
Future Research ◽  
Maternal Cigarette Smoking ◽  
Genome Wide ◽  
A Genome ◽  
Parent Of Origin ◽  
Genetic And Environmental Factors

Background: Although both genetic and environmental factors have been reported to influence the risk of isolated cleft lip with or without cleft palate (CL/P), the exact mechanisms behind CL/P are still largely unaccounted for. We recently developed new methods to identify parent-of-origin (PoO) interactions with environmental exposures (PoOxE) and applied them to families with children born with isolated cleft palate only. Here, we used the same genome-wide association study (GWAS) dataset and methodology to screen for PoOxE effects in the larger sample of CL/P triads. Methods: Genotypes from 1594 complete triads and 314 dyads (1908 nuclear families in total) with CL/P were available for the current analyses. Of these families, 1024 were Asian, 825 were European and 59 had other ancestries. After quality control, 341,191 SNPs remained from the original 569,244. The exposures were maternal cigarette smoking, use of alcohol, and use of vitamin supplements in the periconceptional period. The methodology applied in the analyses is implemented in the R-package Haplin. Results: Among Europeans, there was evidence of a PoOxSmoke effect for ANK3 with three SNPs (rs3793861, q=0.20, p=2.6e-6; rs7087489, q=0.20, p=3.1e-6; rs4310561, q=0.67, p=4.0e-5) and a PoOxAlcohol effect for ARHGEF10 with two SNPs (rs2294035, q=0.32, p=2.9e-6; rs4876274, q=0.76, p=1.3e-5). Conclusion: Our results indicate that the detected PoOxE effects have a plausible biological basis, and thus warrant replication in other independent cleft samples. Our demonstration of the feasibility of identifying complex interactions between relevant environmental exposures and PoO effects offers new avenues for future research aimed at unravelling  the complex etiology of cleft lip defects.

Sign in / Sign up

Export Citation Format

Share Document