Association of the GABRB3 Gene with Nonsyndromic Oral Clefts

2008 ◽  
Vol 45 (3) ◽  
pp. 261-266 ◽  
Author(s):  
Hiroki Inoue ◽  
Shuji Kayano ◽  
Yoko Aoki ◽  
Shigeo Kure ◽  
Atsushi Yamada ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Cleft Palate ◽  
Cleft Lip ◽  
Case Control ◽  
Dinucleotide Repeat ◽  
Aminobutyric Acid ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Oral Clefts

Objective: Nonsyndromic oral clefts are common craniofacial anomalies classified into two subgroups: cleft lip with or without cleft palate and isolated cleft palate. Nonsyndromic oral clefts are multifactorial diseases, with both genetic and environmental factors involved in their pathogenesis. The inhibitory neurotransmitter, γ-aminobutyric acid plays a role in normal embryonic, and particularly facial, development and γ-aminobutyric acid receptor type A β-3 subunit (GABRB3) knockout mice have been shown to have cleft palate. The GABRB3 gene is therefore a strong candidate gene for nonsyndromic oral clefts. We investigated here whether genetic variations of the GABRB3 gene affect the risk for nonsyndromic oral clefts. Method: In this case-control study, a total of 178 Japanese patients with cleft lip with or without cleft palate and 374 unrelated controls were recruited and were genotyped for six single nucleotide polymorphisms and a dinucleotide repeat marker of the GABRB3 gene. Results: None of the single nucleotide polymorphisms showed complete linkage disequilibrium with other single nucleotide polymorphisms. In a case-control association study with the six-locus haplotype of the gene, TGTGCT haplotype frequency in patients with cleft lip with or without cleft palate was significantly higher than in the controls (corrected p value = .029). None of the alleles of the dinucleotide repeat marker showed significant association with cleft lip with or without cleft palate. Conclusions: Our data suggest that the GABRB3 gene is involved in the pathogenesis of cleft lip with or without cleft palate in the Japanese population.

A Mutation in RYK is a Genetic Factor for Nonsyndromic Cleft Lip and Palate

2006 ◽  
Vol 43 (3) ◽  
pp. 310-316 ◽  
Author(s):  
Akira Watanabe ◽  
Sadanori Akita ◽  
Nguyen Thi Duc Tin ◽  
Nagato Natsume ◽  
Yoko Nakano ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Cleft Palate ◽  
Missense Mutation ◽  
Cleft Lip ◽  
Case Control Study ◽  
Case Control ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Transmission Disequilibrium ◽  
Control Study

Objective The RYK, EPHB2, and EPHB3 genes are attractive candidates for cleft lip and/or palate and cleft palate only pathogenesis. Both the Ryk-deficient mouse and Ephb2/Ephb3 (genes for interaction molecules with RYK) double-mutant mouse show cleft palate. Setting Mutation searches for RYK, EPHB2, and EPHB3 were carried out in a large number of Japanese and Vietnamese patients with cleft lip and/or palate and cleft palate only. Case-control study and transmission disequilibrium tests were performed also, using three single nucleotide polymorphisms within a linkage disequilibrium block in RYK. Seven haplotypes were constructed from the single nucleotide polymorphisms. Results A missense mutation, 1355G>A (Y452C), in RYK was identified in one Vietnamese patient with cleft lip and/or palate. This mutation was not found among 1646 Vietnamese, Japanese, and Caucasians, including 354 cleft lip and/ or palate and cleft palate only patients. Colony formation assay using NIH3T3 cells transfected with mutant cDNA revealed that mutant RYK had significantly reduced protein activity, compared with those with wild-type RYK, implying that the transformation ability of RYK is depleted by this mutation. Although a case-control study and transmission disequilibrium tests on three individual single nucleotide polymorphisms provided no evidence for association with oral clefts, a case-control study on one rare haplotype suggested a positive association in Japanese patients with cleft lip and/or palate and cleft palate only. No mutations in EPHB2 and EPHB3 were found in any patients examined. Conclusion The findings suggested that a missense mutation, 1355G>A, and one rare single nucleotide polymorphisms haplotype may play a role in the development of cleft lip and/or palate in the Vietnamese, and cleft lip and/ or palate and cleft palate only in the Japanese.

Association of single nucleotide polymorphisms in WNT genes with the risk of nonsyndromic cleft lip with or without cleft palate

2018 ◽  
Vol 58 (4) ◽  
pp. 130-135 ◽  
Author(s):  
Houshang Rafighdoost ◽  
Mohammad Hashemi ◽  
Hossein Asadi ◽  
Gholamreza Bahari
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Cleft Palate ◽  
Cleft Lip ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Association of Single Nucleotide Polymorphisms on Locus 18q21.1 in the Etiology of Nonsyndromic Cleft Lip Palate (NSCLP) in Indian Multiplex Families

2021 ◽  
Vol 08 (01) ◽  
pp. 024-031
Author(s):  
Praveen Kumar Neela ◽  
Gosla Srinivas Reddy ◽  
Akhter Husain ◽  
Vasavi Mohan ◽  
Sravya Thumoju ◽  
...  
Keyword(s):  
High Risk ◽  
Single Nucleotide Polymorphisms ◽  
Cleft Lip ◽  
Genetic Research ◽  
P Value ◽  
Allelic Association ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Cleft Lip Palate ◽  
Multiplex Families

Abstract Background Cleft lip palate (CLP) is a common congenital anomaly with multifactorial etiology. Many polymorphisms at different loci on multiple chromosomes were reported to be involved in its etiology. Genetic research on a single multigenerational American family reported 18q21.1 locus as a high-risk locus for nonsyndromic CLP (NSCLP). However, its association in multiple multiplex families and Indian population is not analyzed for its association in NSCLP. Aim This study was aimed to evaluate whether high-risk single nucleotide polymorphisms (SNPs) on chromosome 18q21.1 are involved in the etiology of NSCLP in multiplex Indian families. Materials and Methods Twenty multigenerational families affected by NSCLP were selected for the study after following inclusion and exclusion criteria. Genomic DNA was isolated from the affected and unaffected members of these 20 multiplex families and sent for genetic analysis. High-risk polymorphisms, such as rs6507872 and rs8091995 of CTIF, rs17715416, rs17713847 and rs183559995 of MYO5B, rs78950893 of SMAD7, rs1450425 of LOXHD1, and rs6507992 of SKA1 candidate genes on the 18q21.1 locus, were analyzed. SNP genotyping was done using the MassARRAY method. Statistical analysis of the genomic data was done by PLINK. Results Polymorphisms followed the Hardy–Weinberg equilibrium. In the allelic association, all the polymorphisms had a p-value more than 0.05. The odds ratio was not more than 1.6 for all the SNPs. Conclusion High-risk polymorphisms, such as rs6507872 and rs8091995 of CTIF, rs17715416, rs17713847 and rs183559995 of MYO5B, rs78950893 of SMAD7, rs1450425 of LOXHD1, and rs6507992 of SKA1 in the locus 18q21.1, are not associated with NSCLP in Indian multiplex families.

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