Polymorphism of prion protein gene (PRNP) in Nigerian sheep

Abstract

Polymorphism of the prion protein gene (PRNP) gene determines an animal's susceptibility to scrapie. Three polymorphisms at codons 136, 154, and 171 have been linked to classical scrapie susceptibility, although many variants of PRNP have been reported. However, no study has investigated scrapie susceptibility in Nigerian sheep from the drier agro-climate zones. In this study, we aimed to identify PRNP polymorphism in nucleotide sequences of 126 Nigerian sheep by comparing them with public available studies on scrapie-affected sheep. Further, we deployed Polyphen-2, PROVEAN, and AMYCO analyses to determine the structure changes produced by the non-synonymous SNPs. Nineteen (19) SNPs were found in Nigerian sheep with 14 being non-synonymous. Interestingly, one novel SNP (T718C) was identified. There was a significant difference (P < 0.05) in the allele frequencies of PRNP codon 154 between sheep in Italy and Nigeria. Based on the prediction by Polyphen-2, R154H was probably damaging while H171Q was benign. Contrarily, all SNPs were neutral via PROVEAN analysis while two haplotypes (HYKK and HDKK) had similar amyloid propensity of PRNP with resistance haplotype in Nigerian sheep. Our study provides valuable information that could be possibly adopted in programs targeted at breeding for scrapie resistance in sheep from tropical regions.

Keywords: Nigeria; polymorphism; prion protein gene; scrapie; sheep; susceptibility.

Figure 1.

Comparisons of the allele frequencies of PRNP codons 154 and 240 in Central and Southern Italy, Chinese and Nigerian sheep. (a) Comparisons of the allele frequency of the PRNP codon 154 between Central and Southern Italy, Chinese sheep and Nigerian sheep [30,63] (b) Comparisons of the allele frequency of PRNP codon 240 between Chinese and Nigerian sheep [30].

Figure 2.

Prediction of amyloid propensity of sheep prion protein according to nonsynonymous SNPs. AMYCO predicted amyloid propensity as values from 0.0 to 1.0. The AMYCO scores<0.45 and>0.78 indicated low and high aggregation propensities of the protein, respectively. ‘HYNN’ indicates haplotype of serine allele at the codon 139, serine allele at the codon 146, histidine allele at the codon 154, and Isoleucine allele at the codon 193. ‘HYKK’ indicates haplotype of Arginine allele at the codon 139, asparagine allele at the codon 146, arginine allele at the codon 154, and threonine allele at the codon 193. ‘HDKK’ indicates haplotype of arginine allele at the codon 139, asparagine allele at the codon 146, histidine allele at the codon 154, and threonine allele at the codon 193. ‘RYNN’ indicates haplotype of arginine allele at the codon 139, asparagine allele at the codon 146, arginine allele at the codon 154, and isoleucine allele at the codon 193.