👤 A Namipashaki

Nonsyndromic oral clefting (NSOC) is although one of the most common congenital disorders worldwide, its underlying molecular basis remains elusive. This process has been hindered by the overwhelmingly high level of heterogeneity observed. Given that hitherto multiple loci and genes have been associated with NSOC, and that complex diseases are usually polygenic and show a considerable level of missing heritability, we used a systems genetics approach to reconstruct the NSOC network by integrating human-based physical and regulatory interactome with whole-transcriptome microarray data. We show that the network component contains 53% (23/43) of the curated NSOC-implicated gene set and displays a highly significant propinquity (P < 0.0001) between genes implicated at the genomic level and those differentially expressed at the transcriptome level. In addition, we identified bona fide candidate genes based on topological features and dysregulation (e.g. ANGPTL4), and similarly prioritised genes at GWA loci (e.g. MYC and CREBBP), thus providing further insight into the underlying heterogeneity of NSOC. Gene ontology analysis results were consistent with the NSOC network being associated with embryonic organ morphogenesis and also hinted at an aetiological overlap between NSOC and cancer. We therefore recommend this approach to be applied to other heterogeneous complex diseases to not only provide a molecular framework to unify genes which may seem as disparate entities linked to the same disease, but to also predict and prioritise candidate genes for further validation, thus addressing the missing heritability. Show less

In a recent study, a genome-wide scan has identified C771G (His241Gln) polymorphism of MLX interacting protein like (MLXIPL) gene that is associated with the level of plasma triglycerides. Since, no study has been reported on the association between MLXIPL gene and non-alcoholic fatty liver disease (NAFLD), we aimed to identify a connection between this genetic variation and NAFLD. Two hundred and thirteen patients with NAFLD and 252 healthy controls were entered into this study. MLXIPL genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Our study showed that the single nucleotide polymorphism (SNP) of MLXIPL is significantly associated with NAFLD. Significant differences between cases and controls were observed for MLXIPL genotype frequencies (p<0.002). The frequency of C allele of MLXIPL in patient group was higher than the control group (68.30% vs. 51.59%, respectively; p<0.05). C771G polymorphism in the MLXIPL gene potentially plays a significant role in pathophysiology of non-alcoholic fatty liver disease. Further research is needed to confirm this finding. Show less