Current understanding of PrnP Genetics: A tool for Molecular Assisted Selection in Sheep Populations (A review)

Abstract

Scrapie is a neurodegenerative prion disease of sheep, goats and mouflons, belonging to the group of transmissible spongiform encephalopathies (TSEs), which affects humans as well. Even though classical scrapie has been known for over 250 years, the 1985 BSE crisis related to the advent of new forms of the Creutzfeldt-Jakob disease (vCJD) in humans imposed the implementation of rapid coercive legal measures of prevention, control and eradication of TSEs. According to the prion hypothesis, the transmissible agent is the pathological isoform (PrP Sc ) of cellular prion protein (PrP C ). Specific polymorphisms of the gene that encodes cell prion protein (PrnP) in sheep have been associated with resistance / natural susceptibility to the development and progression of the disease. Combinations of alleles at three adjacent codons (136 [A/V], 154 [H/R], 171 [H/Q/R]) underpin the classification of 15 possible genotypes in risk classes, applicable in selection schemes where the maximum resistance is conferred by ARR allele, and the minimum by the VRQ allele. Although, after applying these programmes, the genetic structure of sheep populations has changed favourably, genotype association studies showed that no genotype is completely resistant to the infection, including homozygote ARR / ARR. With the discovery of atypical scrapie (Nor98), it became evident that the connection between the genetics of prion protein gene polymorphisms and susceptibility to the disease must be re-evaluated individually for each breed. In scrapie monitoring and control programmes, three diagnostic categories of the disease are observed: classical scrapie, atypical scrapie and BSE scrapie in small ruminant. This review shows the chronology of progress in the fight for the eradication of TSEs in sheep, 30 years after the BSE epidemic outburst, focusing especially on the link between the molecular diagnostic forms and the genetics of the disease.

Variasi Genotipe dan Alel Gen PIT1|HinfI pada Sapi Perah Friesian Holstein Lokal di Boyolali Jawa Tengah

“…Posisi SNP terletak pada ENSBTAT00000056643.3:c.828G>A (www.ensembl.org) dengan kode akses varian rs134303957 (Ahmadi et al, 2015;Hunt et al, 2018). Lebih lanjut, Cosier and Croitoriu (2012); Ahmadi et al (2015) melaporkan bahwa mutasi pada PIT1|HinfI terjadi akibat substitusi transisi yang tidak menyebabkan perubahan asam amino (synonymous) pada urutan 276 yaitu pada asam amino leusin ENSBTAP00000050905.2:p.Leu276= (www.ensembl.org). Variasi genotipe dan alel gen PIT1 telah dilaporkan oleh beberapa penelitian sebelumnya (Tabel 3).…”

Detecting animal by-product intake using stable isotope ratio mass spectrometry (IRMS)

“…This unique challenge requires the development of novel assays to explore prion protein complexes (Sobrova et al, 2012). Currently diagnostic tests for PDs can only be performed when animals show symptoms or postmortem (Leal et al, 2015;Cosier and Daraban, 2016).…”