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

,Pk Ragunath,Pa Abhinand

doi:10.6026/97320630009610

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

, Pk Ragunath + Show 1 more

Open Access

https://doi.org/10.6026/97320630009610

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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.

Highlights

Epsilon toxin secreted by Clostridium perfringens types B and D has been directly implicated as the causative agent of fatal enterotoxemia in domestic animals
The pMMBltb.Etx40-62 from E. coli DH5α cells was transferred to the Vibrio cholerae JBK70 cells essentially as described earlier [12]
Epitope analysis plays an important role in the development of effective vaccine and diagnostic tools for different infections

Summary

Introduction

Epsilon toxin secreted by Clostridium perfringens types B and D has been directly implicated as the causative agent of fatal enterotoxemia in domestic animals. One of the B cell epitopes of epsilon toxin comprising the region (amino acids 40-62) was identified as a promising antigenic determinant. This Etx epitope (Etx40-62) was cloned and expressed as a translational fusion with B-subunit of heat labile enterotoxin (LTB) of E. coli in a secretory expression system. The rLTB.Etx fusion protein can be evaluated as a potential vaccine candidate against C. perfringens. Of these, Overfeeding of domestic animals leads to an imbalance in gut the Clostridium perfringens type D is a major causative organism microflora and an anaerobic environment that is highly. Large amounts of epsilon toxin produced by the pathogen gets absorbed by the gut mucosa and results in severe vascular damage [3, 4] and lesions in various major organs viz. brain, heart, lung and kidney [5, 6]

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