Objective:To explore the relationship between the polymorphisms in gene FGFR1,FGF10,FGF18 and the nonsyndromic cleft lip with or without cleft palate (NS CLP) in Chinese population. Methods:Genomic DNA was isolated fr...Objective:To explore the relationship between the polymorphisms in gene FGFR1,FGF10,FGF18 and the nonsyndromic cleft lip with or without cleft palate (NS CLP) in Chinese population. Methods:Genomic DNA was isolated from peripheral lymphocytes of 75 patients with NS CLP and their parents and 75 unimpaired healthy children. The polymorphisms in FGFR1 gene rs13317,p.E467K,p.M369I and p.S393S,FGF10 gene rs1448037 and FGF18 gene rs4043716 were detected by applying three-dimensional (3-D) polyacrylamide gel microarray technology. The data were performed using statistical analysis:the genotype frequenc+y and allele frequency between patients with NSCL/P and control subjects were performed. Haplotype relative risk (HRR),family based association test (FBAT),and transmission disequilibrium test (TDT) in nuclear family were performed. Results:There were no polymorphism in FGFR1 gene p.E467K,p.M369I and p.S393S site,the corresponding base was all G. The polymorphisms of rs13317 and rs1448037 were detected and their genotype frequency and allele frequency showed no significant difference between 75 patients with NSCL/P and 75 normal children. TDT,HRR and FBAT were also no significant differences. The genotype frequency of gene FGF18 rs4043716 showed significant difference,but allele frequency were no significant difference. TDT,HRR and FBAT were also no significant difference. Conclusion:Our studies suggest an association between gene FGF18 rs4043716 and the NS CLP in Chinese population,and no association among gene FGFR1 rs13317,p.E467K,p.M369I,p.S393S and gene FGF10 rs1448037.展开更多
Background The receptor tyrosine kinase-like orphan receptor 2 （ROR2） gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non ...Background The receptor tyrosine kinase-like orphan receptor 2 （ROR2） gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans.The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts.Methods Here we tested 38 eligible single-nucleotide polymorphisms （SNPs） in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland.Family Based Association Test was used to test for deviation from Mendelian inheritance.Plink software was used to test potential parent of origin effect.Possible maternally mediated in utero effects were assessed using the TRlad Multi-Marker approach under an assumption of mating symmetry in the population.Results Significant evidence of linkage and association was shown for 3 SNPs （rs7858435,rs10820914 and rs3905385） among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests.P values for these 3 SNPs equaled to 0.000068,0.000115 and 0.000464 respectively which were all less than the significance level （0.05/38=0.0013） adjusted by strict Bonferroni correction.Relevant odds ratios for the risk allele were 3.42 （1.80-6.50）,3.45 （1.75-6.67） and 2.94 （1.56-5.56）,respectively.Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate.Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups.Conclusion Our results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.展开更多
文摘目的探讨全反式维甲酸(at RA)对小鼠胚胎腭突中骨形态发生蛋白受体2(BMPR2)表达的影响。方法通过at RA灌胃的方法建立at RA诱导的小鼠腭裂模型,取妊娠15 d(GD15)和17 d的(GD17)的胚胎腭部进行苏木精-伊红染色,并用免疫组织化学及逆转录聚合酶链式反应技术检测BMPR2在胚胎腭部的表达。结果 at RA诱导小鼠形成体积较小的畸形腭突和明显的中缝腭裂畸形。BMPR2在GD15和GD17正常胚胎腭部有高水平的阳性表达,但在腭裂胚胎腭部的表达水平明显减弱。正常胚胎腭部Bmpr2 m RNA在GD15和GD17的表达水平均明显高于腭裂胚胎(P<0.05)。结论 at RA可导致小鼠胚胎腭突发育不良形成腭裂,并显著下调BMPR2表达水平,从而影响腭部发育的正常分子调控过程。
基金Supported by the Medical Technology Development Foundation of Jiangsu Provincial Health Bureau of China(H200513)~~
文摘Objective:To explore the relationship between the polymorphisms in gene FGFR1,FGF10,FGF18 and the nonsyndromic cleft lip with or without cleft palate (NS CLP) in Chinese population. Methods:Genomic DNA was isolated from peripheral lymphocytes of 75 patients with NS CLP and their parents and 75 unimpaired healthy children. The polymorphisms in FGFR1 gene rs13317,p.E467K,p.M369I and p.S393S,FGF10 gene rs1448037 and FGF18 gene rs4043716 were detected by applying three-dimensional (3-D) polyacrylamide gel microarray technology. The data were performed using statistical analysis:the genotype frequenc+y and allele frequency between patients with NSCL/P and control subjects were performed. Haplotype relative risk (HRR),family based association test (FBAT),and transmission disequilibrium test (TDT) in nuclear family were performed. Results:There were no polymorphism in FGFR1 gene p.E467K,p.M369I and p.S393S site,the corresponding base was all G. The polymorphisms of rs13317 and rs1448037 were detected and their genotype frequency and allele frequency showed no significant difference between 75 patients with NSCL/P and 75 normal children. TDT,HRR and FBAT were also no significant differences. The genotype frequency of gene FGF18 rs4043716 showed significant difference,but allele frequency were no significant difference. TDT,HRR and FBAT were also no significant difference. Conclusion:Our studies suggest an association between gene FGF18 rs4043716 and the NS CLP in Chinese population,and no association among gene FGFR1 rs13317,p.E467K,p.M369I,p.S393S and gene FGF10 rs1448037.
文摘Background The receptor tyrosine kinase-like orphan receptor 2 （ROR2） gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans.The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts.Methods Here we tested 38 eligible single-nucleotide polymorphisms （SNPs） in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland.Family Based Association Test was used to test for deviation from Mendelian inheritance.Plink software was used to test potential parent of origin effect.Possible maternally mediated in utero effects were assessed using the TRlad Multi-Marker approach under an assumption of mating symmetry in the population.Results Significant evidence of linkage and association was shown for 3 SNPs （rs7858435,rs10820914 and rs3905385） among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests.P values for these 3 SNPs equaled to 0.000068,0.000115 and 0.000464 respectively which were all less than the significance level （0.05/38=0.0013） adjusted by strict Bonferroni correction.Relevant odds ratios for the risk allele were 3.42 （1.80-6.50）,3.45 （1.75-6.67） and 2.94 （1.56-5.56）,respectively.Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate.Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups.Conclusion Our results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.
