In silico Analysis of Single Nucleotide Polymorphism in INHA Gene of Sheep and Goats

Inhibin A (INHA) a member of the transforming growth factor-β (TGF-β) family has been implicated in the negative feedback control mechanism of the pituitary follicle stimulating hormone (FSH). Inhibin has been reported to be associated with litter size, milk yield, fertility and reproductive traits in ruminants.

A total of ten amino acid sequences (four sheep and six goats) were downloaded from the National Centre for Biotechnology Information database (http://www.ncbi.nlm.nih.gov/snp). The amino acid sequence alignment was carried out using ClustalW algorithm of Molecular Evolutionary Genetic Analysis software version 6.0. The functional effects of eighteen (18) amino acid substitutions of INHA gene in each of sheep and goats were predicted computationally using Polyphen-2, PROVEAN and SIFT algorithms while INHA gene functions and interactions with associated genes were investigated using GeneMANIA. Variants that were consensually predicted to be deleterious by the three algorithms utilised were referred to as ‘Cmutant’ and ‘Dmutant’ in sheep and goats, respectively. The MutPred was further used to determine the tolerance degree for each amino acid substitution of both the ‘Cmutant’ and ‘Dmutant’.

GeneMANIA revealed 20 genes that co-localised, co-expressed with, play functionally similar role or has physical or genetic interaction with INHA gene. Out of the studied eighteen (18) amino acid substitutions; there was a consensus by SIFT, PROVEAN and PolyPhen-2 algorithms in the prediction of variants C99R, C264D, L237T and F14C as being deleterious in sheep and variants D77F, L190K, R223D, L240N, C322T and P326C in goats. In goats, MutPred revealed that variants R223D and D77F were not harmful while, L190K, R223D, L240N and P326C mutations were observed to be highly harmful. In sheep, the ‘Dmutants’ (C99R, C264D, F14C and L237T) were predicted to be highly harmful. The obtained findings would be useful in planning research aiming at exploring the association between INHA gene variants and economically important traits of small ruminants.