[Association study on microsatellite polymorphisms of MSX1 gene and nonsyndromic cleft lip and palate].
ABSTRACT To investigate muscle segment homeobox 1 (MSX1) microsatellite marker distribution and the relationship between MSX1 gene and the genetic susceptibility of nonsyndromic cleft lip and palate (NSCLP) in Hunan Hans.
One microsatellite DNA marker CA repeat in MSX1 intron region was used as genetic markers. The genotypes of 129 patients with NSCLP and 108 controls were analyzed by the techniques of polymerase chain reaction (PCR) and denaturing polyacrylamide gel electrophoresis (PAGE). Then case-control study was used to conduct association analysis.
The allele frequencies of the CA repeat microsatellite DNA in Hunan Han normal population were in good agreement with Hardy-Weinberg equilibrium. The polymorphism information content and heterozygosity of CA repeat microsatellite DNA were 0.50 and 0.50 respectively. The allele CA4 frequency in CL/P and CPO group was significantly higher than that of normal controls (P<0.05). The genotype CA4,4 frequency was significantly higher in CL/P and CPO group than that in normal controls (P<0.05).
The microsatellite DNA marker CA repeat in MSX1 is a good genetic marker. MSX1 gene is significantly associated with NSCLP in Hunan Hans.
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ABSTRACT: We revisited 42 families with two or more cleft-affected siblings who participated in previous studies. Complete dental information was collected to test the hypothesis that dental anomalies are part of the cleft phenotype spectrum, and can provide new opportunities for identification of cleft susceptibility genes. Genotypes from 1489 single nucleotide polymorphism markers located in 150 candidate genes/loci were reanalyzed. Two sets of association analyses were carried out. First, we ran the analysis solely on the cleft status. Second, we assigned affection to any cleft or dental anomaly (tooth agenesis, supernumerary teeth, and microdontia) and repeated the analysis. Significant over-transmission was seen for a single nucleotide polymorphism in ankyrin repeat and sterile alpha motif domain containing 6 (rs4742741, 9q22.33; P = 0.0004) when a dental anomaly phenotype was included in the analysis. Significant over-transmission was also seen for a single nucleotide polymorphism in ERBB2 (rs1810132, 17q21.1; P = 0.0006). In the clefts only data, the most significant result was also for ERBB2 (P = 0.0006). Other markers with suggestive P values included interferon regulatory factor 6 and 6q21-q23 loci. In contrast to the above results, suggestive over-transmission of markers in GART, DPF3, and neurexin 3 were seen only when the dental anomaly phenotype was included in the analysis. These findings support the hypothesis that some loci may contribute to both clefts and congenital dental anomalies. Thus, including dental anomalies information in the genetics analysis of cleft lip and palate will provide new opportunities to map susceptibility loci for clefts.Genetics in medicine: official journal of the American College of Medical Genetics 10/2008; 10(9):668-74. · 3.92 Impact Factor
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ABSTRACT: Based on association and sequencing studies, investigators have postulated muscle segment homeobox 1 (MSX1) as a strong candidate gene involved in the causation of nonsyndromic cleft lip with or without cleft palate (NSCLP). Parent-of-origin effects have been suggested for some NSCLP candidate genes but not for MSX1. The aims of the present study were to test for allele/haplotype associations applying the transmission disequilibrium test (TDT) and the transmission asymmetry test (TAT) to evaluate the possible parent-of-origin effects of MSX1 in Chilean patients with NSCLP. We analyzed five SNPs (rs6446693/c.-425G>T/c.-35G>A/rs3775261/rs12532) located from 6.3 kb upstream to 3' UTR in a sample of 150 unrelated NSCLP case-parent trios. Four haplotypes showed overtransmission from parents to affected progeny, but individual SNPs did not. Two haplotypes presented allele combination C-G-A-G (P = 0.035) and two T-G-C-A (P = 0.044) (SNP order rs6446693/c.-35G>A/rs3775261/rs12532). The rs12532 A allele had a 2.08-fold increase in the risk of NSCLP when inherited from the father (95% CI: 1.10-4.02; P = 0.025), but not from the mother. These results could indicate epigenetic control by imprinting in the role of MSX1 in NSCLP. Different authors have proposed that some genes that play a role in NSCLP depend on parental origin. Our findings and those previously reported by our group show that a variety of factors appears to be involved in the association between MSX1 and NSCLP. The full mechanism of MSX1 in the development of NSCLP has not been fully understood.American Journal of Medical Genetics Part A 08/2010; 152A(8):2011-6. · 2.30 Impact Factor
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ABSTRACT: Nonsyndromic oral clefts (NSOC) are the most common craniofacial birth defects in humans. The etiology of NSOC is complex, involving both genetic and environmental factors. Several genes that play a role in cellular proliferation, differentiation, and apoptosis have been associated with clefting. For example, variations in the homeobox gene family member MSX1, including a CA repeat located within its single intron, may play a role in clefting. The aim of this study was to investigate the association between MSX1 CA repeat polymorphism and NSOC in a Southern Brazilian population using a case-parent triad design. We studied 182 nuclear families with NSOC recruited from the Hospital de Clínicas de Porto Alegre in Southern Brazil. The polymorphic region was amplified by the polymerase chain reaction and analyzed by using an automated sequencer. Among the 182 families studied, four different alleles were observed, at frequencies of 0.057 (175 bp), 0.169 (173 bp), 0.096 (171 bp) and 0.67 (169 bp). A transmission disequilibrium test with a family-based association test (FBAT) software program was used for analysis. FBAT analysis showed overtransmission of the 169 bp allele in NSOC (P=0.0005). These results suggest that the CA repeat polymorphism of the MSX1 gene may play a role in risk of NSOC in populations from Southern Brazil.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 07/2013; · 1.08 Impact Factor