Genetic Resistance to Prion Diseases

Abstract

Prions are abnormal isoforms of the host-encoded cellular prion proteins which are misfolding in its three-dimensional structure acquire pathogenicity. Prions cause transmissible spongiform encephalopathy (TSEs) in humans and some animal species including sheep, goats, catle, cat, deer and elk. TSEs, also called "prion diseases," cause irreversible neurodegeneration in the central nervous system and are always fatal. Cellular prion proteins are encoded by prion protein gene (PRNP) in mammals; moreover, it is known that the variations in the PRNP gene have inluence on the resistance and/or incubation period of the TSEs. It is well-documented that after exposure to the pathogenic prions, development of some TSEs depend on the host PRNP genotype, for example, scrapie in sheep, bovine spongiform encephalopathy (BSE) in catle, Creuzfeldt-Jakob disease (CJD) and kuru in humans, as well. In this chapter, genetic resistance to prion diseases will be reviewed.Keywords: TSE, prion disease, PRNP, genetic resistance IntroductionIt is known that conformational changes in prion protein cause Creuzfeldt-Jakob disease (CJD) in humans, scrapie disease in sheep and goats [1,2], bovine spongiform encephalopathy (BSE) in catle, feline spongiform encephalopathy in cat, and wasting disease in deer and elk.Polymorphisms inside the prion protein-coding gene (PRNP) in humans and also in some mammalian species have been appeared to impact disease susceptibility and pathologies [3]. In human population, kuru and CJD are profoundly related with polymorphism in codon 129. All CDJ afected individuals are known to be homozygous for methionine amino acid in codon 129 while at the same codon heterozygote individuals seem most resistant to kuru [4,5]. Also, it is known that there is a high correlation between the polymorphisms in codons © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.136, 154, and 171 of the PRNP gene and the level of susceptibility to scrapie in sheep [3,6,7]. In catle, numerous studies were carried out for discovering a relationship amongst BSE and polymorphisms in catle genome [8][9][10][11][12]. The studies about BSE-afected animals in Germany and USA represented the inluence of PRNP promoter polymorphisms on BSE susceptibility in catle [13,14]. The impacts of insertion-deletion (indel) polymorphisms within a location 1.6 kbp upstream of exon 1 and inside intron 1 (23-bp and 12-bp, respectively) on BSE susceptibility are determined by further analyses in catle [15][16][17]. Despite the fact that catle with the -/-23 bp promoter genotype and the -/12 bp intron 1 genotype have both been signiicantly connected with BSE, it could not be reached any consensus on which genotype is most identiied with BSE [13,15,16,18]. In addition, indel polymorphisms that afect the sensitivity o...