Linkage evidence and methylation at 2q region in nonsyndromic cleft lip and/or palate of Malay population

Abstract

Introduction: Nonsyndromic cleft lip and/or palate (NSCLP) occurs as a result of multifactorial determinants, involving both genetic and environmental factors. Several candidate genes associated with NSCLP have been discovered through genetic approach, but there is paucity of studies focusing on epigenetic determinants in NSCLP. We are interested to reveal linkage evidence of SATB2 at 2q region in large-extended NSCLP families of Malay population and its methylation activity in causing cleft formation. Materials and Methods: Eight large-extended families were included in this study. Microarray analysis was carried out and genome-wide linkage was determined using GeneHunter Multipoint Linkage Analysis v2.1r5. SATB2 methylation was tested on 100 NSCLP patients by DNA sequencing. Results: Genome-wide linkage analysis has revealed significant nonparametric linkage score and suggestive logarithm of the odds (LOD) score at 2q region in family 50 and family 100. Genome-wide heterogeneity LOD score of 2.63 and α =0.122 were found in total families at 2q33.1-q35 region. Significant copy number loss (P < 0.05) in NSCLP family compared with the normal control supports the linkage evidence of SATB2 in those families with positive linkage. Epigenetic testing found SATB2 unmethylation at DNA promoter region. Discussion: Linkage evidence and significant low copy number of SATB2 in NSCLP family of Malay population confirmed that genetic factors play a major role in causing cleft defects. SATB2 unmethylation could not support the epigenetic occurrence in causing craniofacial deformities. Conclusions: Linkage evidence and significant low copy number of SATB2 in NSCLP family of Malay population confirmed that genetic factors play a major role in causing cleft defects. SATB2 unmethylation could not support the epigenetic occurrence in causing craniofacial deformities.