In-SilicoAnalysis of Deleterious Mutations in Serum Amyloid A3 Gene in Goats

Abstract

Serum amyloid A3 (SAA3) protein found within caprine mammary epithelial cells is said to be important in disease conditions and tissue remodeling. The present investigation aimed at identifying deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in SAA3 gene of goats using an in silico assay. Amino acid sequence data of the protein were retrieved from the National Centre for Biotechnology Information (NCBI) website and aligned to obtain amino acid substitutions. Bioinformatics prediction tools used for the detection of deleterious nsSNPs were PROVEAN, SIFT, PolyPhe-2 and PANTHER. A total of eleven nsSNPs were obtained, out of which two variants (R123G and G126D) were predicted to be deleterious by three out of the four algorithms. The mutants were also found to decrease protein stability. Further confirmatory analysis however, revealed that variant R123G was highly deleterious as there were marked differences between it and the native protein in terms of total free energy, stabilizing residues, ordered and disordered regions of protein and secondary structure prediction. Similarly, Cmutant (a combination of R123G and G126D mutations) was also found to distort SAA3 protein structural landscape and function. The present deleterious nsSNPs when validated using wet lab experimental protocols could be important biological markers for disease detection and therapy in goats.