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Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method
Published on: September 16, 2017
Genetic characterization and evolutionary inference of TNF-alpha through computational analysis
Gauri Awasthi1, Suchita Singh, A P Dash
1National Institute of Malaria Research, Delhi, India.
Tumor Necrosis Factor-alpha (TNF-alpha) exhibits dual roles in malaria, with high doses causing severe disease and low doses offering protection. Evolutionary analysis of the TNF-alpha gene suggests its unique role in this dualistic pathogenicity.
Area of Science:
- Evolutionary biology
- Immunology
- Genetics
Background:
- Tumor Necrosis Factor-alpha (TNF-alpha) is a key human cytokine with a complex role in malaria pathogenicity.
- High concentrations of TNF-alpha are linked to cerebral malaria, while lower concentrations are protective against severe malaria.
Purpose of the Study:
- To investigate the evolutionary aspects of the dualistic nature of the human TNF-alpha gene in malaria pathogenicity.
- To perform a detailed characterization of the TNF-alpha gene across various mammalian and avian taxa.
Main Methods:
- Comparative analysis of nucleotide length variations, intron/exon sizes, and base composition of the TNF-alpha gene in seven taxa.
- Phylogenetic analysis of TNF-alpha gene sequences.
- Alignment of amino acid sequences and comparison of coding/non-coding nucleotide variations between TNF-alpha and TNF-beta in selected mammalian taxa.
Main Results:
- Phylogenetic analysis clustered humans, chimpanzees, and rhesus monkeys together, separate from rats/mice, with chickens forming a distinct branch.
- Amino acid sequences showed minor differences between humans and chimpanzees, and greater differences with rhesus monkeys.
- Comparisons indicated that the TNF-alpha gene, not TNF-beta, plays a role in the dualistic nature of malaria pathogenicity.
Conclusions:
- The study provides insights into the evolutionary patterns of the TNF-alpha gene.
- Evidence suggests the TNF-alpha gene, specifically, is responsible for its dual role in malaria pathogenicity, distinguishing it from its duplicate, TNF-beta.
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