Systems biological approach to investigate the lack of familial link between Down's Syndrome & Neural Tube Disorders

Systems Biology involves the study of the interactions of biological systems and ultimately their functions. Down''s syndrome (DS)is one of the most common genetic disorders which are caused by complete, or occasionally partial, triplication of chromosome 21,characterized by cognitive and language dysfunction coupled with sensory and neuromotor deficits. Neural Tube Disorders(NTDs) are a group of congenital malformations of the central nervous system and neighboring structures related to defectiveneural tube closure during the first trimester of pregnancy usually occurring between days 18-29 of gestation. Several studies in thepast have provided considerable evidence that abnormal folate and methyl metabolism are associated with onset of DS & NTDs.There is a possible common etiological pathway for both NTDs and Down''s syndrome. But, various research studies over the yearshave indicated very little evidence for familial link between the two disorders. Our research aimed at the gene expression profilingof microarray datasets pertaining to the two disorders to identify genes whose expression levels are significantly altered in theseconditions. The genes which were 1.5 fold unregulated and having a p-value <0.05 were filtered out and gene interaction networkwere constructed for both NTDs and DS. The top ranked dense clique for both the disorders were recognized and overrepresentation analysis was carried out for each of the constituent genes. The comprehensive manual analysis of these genes yieldsa hypothetical understanding of the lack of familial link between DS and NTDs. There were no genes involved with folic acidpresent in the dense cliques. Only – CBL, EGFR genes were commonly present, which makes the allelic variants of these genes –good candidates for future studies regarding the familial link between DS and NTDs.

Abbreviations

NTD - Neural Tube Disorders, DS - Down''s Syndrome, MTHFR - Methylenetetrahydrofolate reductase, MTRR– 5 - methyltetrahydrofolate-homocysteine methyltransferase reductase.