Disease relevance of PRNP

• We isolated blood samples from 222 sheep representing the eight main local sheep breeds in the Xinjiang Autonomous Region, the territory with the most abundant local sheep breeds in China, to identify the PRNP polymorphisms and to determine whether these breeds were at risk for developing scrapie [1].
• Oral contamination with bovine spongiform encephalopathy (BSE) agent in susceptible PRNP genotype sheep results in widespread distribution of prion in the host [2].
• Susceptibility to this neurodegenerative disease is controlled mainly by point mutations at the PRNP locus [3].
• Polymorphisms in the prion protein gene (PRNP) in humans and sheep correlate with susceptibility to transmissible spongiform encephalopathies (TSEs) [4].

Psychiatry related information on PRNP

• These data imply that homozygosity for Q-171 codons is necessary but not sufficient for the development of natural scrapie, echo reports of recessive manifestation, and parallel over-representation of PRNP codon 129 homozygotes in Creutzfeldt-Jakob disease of humans [5].

High impact information on PRNP

• Similar genetic differences exist in sheep, in which PRNP polymorphisms modify the susceptibility to scrapie [6].
• In intestinal lymph nodes, expression levels differed between the different PRNP genotypes [6].
• However, the known coding polymorphisms within the bovine PRNP gene have little or no effect on bovine spongiform encephalopathy (BSE) susceptibility in cattle [6].
• In prion diseases the lethal evolution is associated with formation of PrP(Sc), a misfolded and amyloid form of the normal cellular prion protein PrP [7].
• Detailed RNA-transcription and protein-expression analysis of one PRNP+/- goat showed that one allele of the caprine PRNP gene had been disrupted functionally [8].

Biological context of PRNP

• The haplotype encoding amino acid residues A, R, and Q at codons 136, 154, and 171, respectively, was observed on nine larger haplotypes spanning PRNP from the promoter region to the 3' untranslated region [9].
• Single nucleotide polymorphisms (SNPs) and haplotype alleles within the prion gene (PRNP) coding sequence of domestic sheep (Ovis aries) are associated with genetic predisposition to scrapie, a transmissible spongiform encephalopathy disease of sheep [9].
• The haplotype structure within the 20-kbp region of PRNP identified in this study is important for higher-resolution analysis of genetics contributions to scrapie susceptibility [9].
• Four sequence tagged sites (i.e., STS or amplicons) totaling 3869 bp and spanning 20 kbp of genomic PRNP sequence were sequenced in a diverse panel of 90 sires representing ten popular U.S. breeds of sheep [9].
• This report describes regions of linkage disequilibrium (LD) throughout the PRNP gene region in U.S. sheep and provides a genetic framework for identifying additional PRNP determinants associated with scrapie resistance [9].

Anatomical context of PRNP

• Haplotypes of the 3 PRNP codons were determined for each sheep, and breed of origin of each gamete was predicted by genotyping 6 microsatellite markers flanking the PRNP locus [10].
• One possibility for the lack of PrP(Sc) accumulation in brains and lymph nodes of scrapie-exposed sheep with 171RR PRNP genetics is because of fewer PrPc-positive myeloid-derived cells available for conversion of PrPc to PrP(Sc) [11].
• Using flow cytometric analysis, statistically fewer PrPc-positive microglia and monocytes were observed from sheep with 171RR PRNP genetics than from sheep with 171QQ PRNP genetics (P<0.05) [11].
• Further search of PrP(C)-interacting molecules and detailed studies using Prnp(-/-) mice and various type of Prnp(-/-) cell lines under various conditions are the prerequisites in elucidating PrP functions [12].

Associations of PRNP with chemical compounds

• A new PRNP polymorphism encoding either glycine (G) or arginine (R) at codon 85 as well as eight previously reported polymorphisms at codons 101, 112, 127, 141, 146, 154, 171, and 189 in other sheep breeds were detected [1].
• A study of the effect of trimethylamine N-oxide on the stability of two recombinant forms of the prion protein PrP, an ovine full-length and a human truncated form, is here reported [13].
• Four single nucleotide polymorphisms (G11A, G615C, G684A, T726G) in the ORF of the porcine PRNP gene were found, and the G-->C nucleotide substitution resulted in a serine to asparaginate amino acid substitution at codon 4 [14].

Regulatory relationships of PRNP

• Polymorphisms of the prion protein gene PRNP have been shown to influence the susceptibility/resistance to prion infections in human and sheep [15].

Analytical, diagnostic and therapeutic context of PRNP

• METHODS: A dual fluorescent multiprobe assay consisting of 2 closed tube PCR reactions containing respectively 4 and 3 dual-labelled fluorescent ASO probes for the detection in real-time of the 7 allelic variants of sheep PRNP mentioned above [16].
• Here, five live PRNP+/- goats cloned by gene targeting are reported [8].

References