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

Abstract

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 defective neural tube closure during the first trimester of pregnancy usually occurring between days 18-29 of gestation. Several studies in the past 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 years have indicated very little evidence for familial link between the two disorders. Our research aimed at the gene expression profiling of microarray datasets pertaining to the two disorders to identify genes whose expression levels are significantly altered in these conditions. The genes which were 1.5 fold unregulated and having a p-value <0.05 were filtered out and gene interaction network were constructed for both NTDs and DS. The top ranked dense clique for both the disorders were recognized and over representation analysis was carried out for each of the constituent genes. The comprehensive manual analysis of these genes yields a hypothetical understanding of the lack of familial link between DS and NTDs. There were no genes involved with folic acid present 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.AbbreviationsNTD - Neural Tube Disorders, DS - Down's Syndrome, MTHFR - Methylenetetrahydrofolate reductase, MTRR– 5 - methyltetrahydrofolate-homocysteine methyltransferase reductase.

Deciphering the cross-talking of human competitive endogenous RNAs in K562 chronic myelogenous leukemia cell line

“…Transcripts present in the dense clique are the most interconnected, hence, belong to the center of the etiological pathway underlying any disease. 50…”

Women with Methylenetetrahydrofolate Reductase Gene Polymorphism and the Need for Proper Periconceptional Folate Supplementation

“…DS results from an over-expression of three extra copies of the gene on chromosome 21 causing failure of normal chromosomal separation during meiosis [21,51,52]. DS affects approximately 1 in 1000 to 1100 live births worldwide and 1 out of every 700 newborns in the US [53,54]. An important risk factor for DS is advanced maternal age at the time of conception [51,52].…”

“…Women who are 35 years or older are more at an increased risk of having a child with DS, however DS children have been born to younger mothers [55][56][57][58]. Studies have shown that mothers of children with DS have abnormal folate metabolism, high homocysteine and hypomethylation similar to NTDs, which result in abnormal gene expression and chromosomal segregation [20,50,53,59].…”