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Insertion or deletion of single copy of octapeptide repeat (OR) in human PrP protein are considered as polymorphism, while of insertions of more numbers of OR and deletion of two copies of OR are associated with genetic prion diseases.Here, we reported a 58-year-old female patient who displayed clinical manifestations of Parkinson's disease (PD) but contained deletion mutation of single copy of OR in one PRNP allele. The patient complained involuntary tremor of left upper limb for 18 months and her symptoms aggravation for 6 months at the time referring to Chinese National CJD surveillance system. The tremor was pronounced at rest, exacerbated by stress and disappear during sleep. Her symptoms were partially relieved after receiving medicament for PD. Neurological examination recorded involuntary movement of left hand and gear-like muscle tension of left upper limb. Coordination movement reported positive of Romberg sign and unstable in heel-keen test. EEG recorded a mild abnormality, but without periodic sharp wave complexes (PSWC). MRI showed a mild write matter demyelination. CSF protein 14-3-3 was negative. PRNP sequencing revealed heterozygosity of single copy deletion on ORs (R1-2-3-4/R1-2-2-3-4).No family history of neurodegenerative disease was recorded. Such case with a single copy of OR deletion in PRNP displaying the feature of PD is rarely reported in Chinese mainland.

Human genetic prion diseases (gPrDs) are directly associated with mutations and insertions in the PRNP (Prion Protein) gene. We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020. Nineteen different subtypes were identified and gPrDs accounted for 10.9% of all diagnosed PrDs within the same period. Some subtypes of gPrDs showed a degree of geographic association. The age at onset of Chinese gPrDs peaked in the 50-59 year group. Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI) cases usually displayed clinical symptoms earlier than genetic Creutzfeldt-Jakob disease (gCJD) patients with point mutations. A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients. None of the E196A gCJD patients reported a family history. The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD (sCJD). EEG examination was not sensitive for gPrDs. sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients. CSF 14-3-3 positivity was frequently detected in gCJD patients. Increased CSF tau was found in more than half of FFI and T188K gCJD cases, and an even higher proportion of E196A and E200K gCJD patients. 63.6% of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC. GSS and FFI cases had longer durations than most subtypes of gCJD. This is one of the largest studies of gPrDs in East Asians, and the illness profile of Chinese gPrDs is clearly distinct. Extremely high proportions of T188K and E196A occur among Chinese gPrDs; these mutations are rarely reported in Caucasians and Japanese., (© 2021. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Objective: To identify the features of Chinese genetic prion diseases., Methods: Suspected Creutzfeldt-Jakob disease (CJD) cases that were reported under CJD surveillance were diagnosed and subtyped using the diagnostic criteria issued by the WHO. The general information concerning the patient, their clinical, MRI and EEG data, and the results of CSF 14-3-3 and PRNP sequencing were carefully collected from the database of the national CJD surveillance program and analyzed using the SPSS 11.5 statistical software program., Results: Since 2006, 69 patients were diagnosed with genetic prion diseases and as having 15 different mutations. The median age of the 69 patients at disease onset was 53.5 years, varying from 19 to 80 years. The majority of patients displaying clinical symptoms were in the 50-59 years of age. FFI, T188K gCJD and E200K were the three most common subtypes. The disease appeared in the family histories of 43.48% of the patients. The clinical manifestations varied considerably among the various diseases. Patients who carried mutations in the N-terminus displayed a younger age of onset, were CSF 14-3-3 negative, had a family history of the condition, and experienced a longer duration of the condition. The clinical courses of T188K were significantly shorter than those of FFI and E200K gCJD, while the symptoms in the FFI group appeared at a younger age and for a longer duration. Moreover, the time intervals between the initial neurologist visit to the final diagnosis were similar among patients with FFI, T188K gCJD, E200K gCJD and other diseases., Conclusion: The features of Chinese genetic prion diseases are different from those seen in Europe and other Asian countries.

Here, polymorphisms of the ovine prion protein gene were analyzed in 486 Chinese sheep from 16 main local breeds. Polymorphisms R or H at codons 154 and four polymorphisms at codon 171 encoding Q, R, H, or K were identified. The A/V polymorphism at codon 136 was not observed, and all sheep were homozygous for A at this position. In addition, ten polymorphisms at codons 21, 101, 112, 127, 138, 141, 143, 146, 153 and 189 were detected. The predominant Q allele occurred at codon 171, with a high frequency of 88.68 %, implying a risk of scrapie in China.

Prion diseases are a group of human and animal neurodegenerative disorders caused by the deposition of an abnormal isoform prion protein (PrP(Sc)) encoded by a single copy prion protein gene (PRNP). Prion disease has been reported in many herbivores but not in Equus and the species barrier might be playing a role in resistance of these species to the disease. Therefore, analysis of genotype of prion protein (PrP) in these species may help understand the transmission of the disease. Xiji donkey is a rare species of Equus not widely reared in Ningxia, China, for service, food and medicine, but its PRNP has not been studied. Based on the reported PrP sequence in GenBank we designed primers and amplified, cloned and sequenced the PRNP of Xiji donkey. The sequence analysis showed that the Xiji donkey PRNP was consisted of an open reading frame of 768 nucleotides encoding 256 amino acids. Amino acid residues unique to donkey as compared with some Equus animals, mink, cow, sheep, human, dog, sika deer, rabbit and hamster were identified. The results showed that the amino acid sequence of Xiji donkey PrP starts with the consensus sequence MVKSH, with almost identical amino acid sequence to the PrP of other Equus species in this study. Amino acid sequence analysis showed high identity within species and close relation to the PRNP of sika deer, sheep, dog, camel, cow, mink, rabbit and hamster with 83.1-99.7% identity. The results provided the PRNP data for an additional Equus species, which should be useful to the study of the prion disease pathogenesis, resistance and cross species transmission., (© 2013 Elsevier B.V. All rights reserved.)

Fatal familial insomnia (FFI) is a special subtype of genetic human prion diseases that is caused by the D178N mutation of the prion protein gene (PRNP). According to the surveillance data from 2006, FFI accounts for about half of all genetic prion disease cases in China. In this study, global expression patterns of the thalamus and parietal cortex from three patients with FFI were analyzed by Affymetrix Human Genome U133+ 2.0 chip. A total of 1,314 genes in the thalamus and 332 ones in the parietal lobe were determined to be differentially expressed genes (DEGs). The percentage of upregulated DEGs is much less in the thalamus (19.3 %) than that in the parietal lobe (42.8 %). Moreover, 255 of those DEGs showed the same altering tendencies in both tested regions, including 99 upregulated and 156 downregulated ones. The reliability of the results was confirmed by the real-time RT-PCR assays. There were 1,152 and 531 biological processes affected in the thalamus and the parietal lobe, respectively, as well as 391 overlapping ones in both regions. The most significantly changed molecular functions included transcription and DNA-dependent regulation of transcription, RNA splicing, mitochondrial electron transport, etc. The changed functions in the thalamus contained more numbers of DEGs than parietal lobe. According to KEGG classification, there were 167 and 115 different pathways changed in the thalamus and the parietal lobe, respectively, while 102 were changed in both. Interestingly, the top three changed pathways in the three groups mentioned above were Parkinson's disease, Alzheimer's disease, and oxidative phosphorylation. These results demonstrate the greater damage in the thalamus than in the parietal lobe during FFI pathogenesis, which is consistent with previous pathological observations. This study aims to describe the global expression profiles in various brain regions of FFI while proposing useful clues for understanding the pathogenesis of FFI and selecting potential biomarkers for diagnostic and therapeutic tools.

Polymorphism of the prion protein gene (PRNP) is usually associated with scrapie susceptibility or resistance. To determine the variability of PRNP in Chinese indigenous goat breeds, we isolated genomic DNA from goat blood and amplified and sequenced the coding region of the gene. We identified 10 polymorphic sites that gave rise to 28 haplotypes. Clear frequency differences were found between northern and southern breeds and confirmed by genetic distance analysis, except for the Tangshan dairy goat. Phylogeographic analysis supported the idea that northern and southern breeds might be considered separate clusters, except for the Tangshan dairy goat. The finding of significant differences in allele distribution in northern and southern goats, especially if involved in modulating resistance/susceptibility, needs to be carefully considered for the feasibility of selection plans for resistance to scrapie.

Eight cases of rare genetic Creutzfeldt-Jakob disease (gCJD) with a mutation T188K in PRNP have been identified and diagnosed genetically in China since 2006. Among the eight cases, the median age of disease onset was 58years old (ranging from 39 to 76years old). Progressive dementia and pyramidal or extrapyramidal dysfunction appeared in all cases and lasted during the entire clinical course. Myoclonus and visual or cerebellar disturbances were also frequently observed. The median duration of disease was 3months. Cerebral MRI findings revealed high caudate and putamen signals in four out of eight cases. CSF in six out of eight patients tested positive for the 14-3-3 protein. Only one case showed periodic sharp-waves (PSW) in EEG. Most cases lacked a family history of associated diseases, though one patient's mother died of a neurologic disorder without a definite diagnosis. Our data reveal that Chinese T188K gCJD cases have clinical characteristics similar to that of sporadic CJD (sCJD). Compared with other inherited prion disease-associated mutations in China, the genetic frequencies of T188K in PRNP of Han-Chinese are relatively high., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In this study, a novel 28-bp insertion-deletion (indel) polymorphism (AJ298878:g.47836-47853insCCTCAGACACTGAGTCTCCCCAACAGCA) was found in goat prion protein (PRNP) gene in 2373 goats from 13 Chinese native breeds. The frequencies of allele "ins" varied from 0.500 to 1.000 in different breeds. The establishment of association of the 28-bp indel polymorphism with production traits was performed in Inner Mongolia white cashmere (IMWC) and Xinong Sannen dairy (XNSN) breeds. Two significant associations between this polymorphism and 1-year-old body mass (P = 0.011) and average body mass (P = 0.024) were observed in IMWC breed, as well as wool thickness of 3-year-olds (P < 0.001). Furthermore, the novel 28-bp indel polymorphism was significantly associated with total solids in the evening (%) (P = 0.009) and milk yield (P = 0.016) in XNSN breed. These findings suggested that the 28-bp indel polymorphism was a potential DNA marker for eliminating or selecting preferred individuals in relation to production traits in goat marker-assisted selection breeding while carrying out preventing scrapie project.

Anti-scrapie breeding programs have been initiated to screen for scrapie-resistant sheep based on ovine prion protein gene (PRNP) genotypes at codons 136, 154 and 171 in many countries, especially European Union member states. However, investigation of sheep PRNP genotypes is limited in China, despite the large number of sheep breeds. We analyzed 432 sheep of five different breeds from farms in northwestern China, using PCR-single-strand conformational polymorphism analysis (PCR-SSCP); the corresponding haplotypes of different PRNP alleles were cloned. PRNP allele genotyping was done by amplification refractory mutation system-PCR (ARMS-PCR), according to the haplotype clones of each PRNP allele. The validity of ARMS-PCR was checked by PCR-SSCP. Another 325 unknown PRNP genotypes of other sheep breeds were analyzed according to the established ARMS-PCR. Genotype frequencies of 757 sheep were analyzed with these two methods to evaluate susceptibility to scrapie in northwestern China. Relevant mutations were also detected at other sites. Both methods were effective for ovine PRNP allele genotyping, and the results of the analysis completely coincided. Scrapie-resistant genotypes were found to be uncommon, indicating a high risk for ovine scrapie in northwest China. In addition to codons 136, 154 and 171, we found numerous new mutations; nearly half of them were previously unreported. These sheep populations have a high degree of polymorphism at the PRNP locus.

The key point, which is related to the susceptibility of prion diseases in animals, has been proved to be the prion protein gene (PRNP). However, animals, especially sheep and goats, with the same PRNP genotype are not equally susceptible to the diseases. The finding of SPRN (shadow of prion protein homology) provides a new aspect to understand the diseases as protein of SPRN (Shadoo) has similar neuroprotective function and conserved hydrophobic core with prion protein (PrP). Researchers have made some efforts to demonstrate the relationship between SPRN and PRNP. Stewart's work has shown that SPRN contained an alanine-rich sequence, which is homologous to a hydrophobic core with amyloidgenic characteristics in PrP. Here our work shows that the sheep of Inner Mongolia in China have several haplotypes with the similar results of Stewart and Daude's. However we find a new haplotype in a Sunite sheep, which is not reported by others.

In this study, genetic variability at codon 42 within prion protein (PRNP) gene and its associations with production traits were investigated in 2002 goats from four Chinese domestic breeds. The frequencies of allele "A" ranged from 0.353 to 0.562 in analyzed goat breeds with Hardy-Weinberg equilibrium (P > 0.05) except Xinong Sannen (XNSN) dairy breed. The establishment of relationships between different genotypes and growth traits was performed in Inner Mongolia white Cashmere (IMWC) breed and revealed an association of the polymorphism with body weight at 7-year-old goats (P = 0.033). The individuals with genotype GG showed heavier body weight than those with genotype AA. Moreover, association analysis detected two significant associations between different genotypes and cashmere yield and fiber length in IMWC breed (P = 0.009, P = 0.048, respectively). In addition, three significant associations of different genotypes with density of milk (a.m. and p.m.), solids-not-fat of milk (P = 0.013, P = 0.009 and P = 0.002), respectively, were found in XNSN breed. Genotype GG had better milk quality than others. These findings suggested that the polymorphism of codon 42 within PRNP was a useful DNA marker for eliminating or selecting excellent individuals in relation to production traits in marker-assist selection breeding of goat.

The resistance or susceptibility of sheep to scrapie is associated with polymorphisms of the prion protein gene (PRNP), particularly, single nucleotide polymorphisms (SNPs) in amino acid positions 136, 154 and 171. The prion protein (PrP) gene sequence and the deduced amino acid alignment of prion protein in Tan sheep, a local Chinese sheep breed traditionally raised in Ningxia, northwestern China, were determined and variability of the PrP amino acids sequence was analyzed in this study. The PrP nucleic acids and amino acids sequences of 112 Tan sheep were highly homogenous, although polymorphism of the PrP gene was detected at several sites, particularly codons 106, 154, and 171. The analysis of both sequences revealed that the most predominant allele at codons 136, 154 and 171 in Tan sheep was ARQ, which was known to be associated with high susceptibility to scrapie in sheep. The result suggests that Tan sheep is potentially susceptible to scrapie. Our findings provide valuable information for future breeding projects to scrapie resistance in Tan sheep., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Two insertion/deletion (indel) polymorphisms of the prion protein gene (PRNP), a 23-bp indel in the putative promoter region and a 12-bp indel within intron I, are associated with the susceptibility to bovine spongiform encephalopathy (BSE) in cattle. In the present study, the polymorphism frequencies of the two indels in four main beef cattle breeds (Hereford, Simmental, Black Angus, and Mongolian) from North China were studied. The results showed that the frequencies of deletion genotypes and alleles of 23- and 12-bp indels were lower, whereas the frequencies of insertion genotypes and alleles of the two indels were higher in Mongolian cattle than in the other three cattle breeds. In Mongolian cattle, the 23-bp insertion / 12-bp insertion was the major haplotype, whereas in Hereford, Simmental, and Black Angus cattle, the 23-bp deletion / 12-bp deletion was the major haplotype. These results demonstrated that Mongolian cattle could be more resistant to BSE, compared with the other three cattle breeds, because of its relatively low frequencies of deletion genotypes and alleles of 23- and 12-bp indel polymorphisms. Thus, this race could be important for selective breeding to improve resistance against BSE in this area.

It is well known that scrapie is a fatal, neurodegenerative disease in sheep and goat, which belongs to the group of transmissible spongiform encephalopathies (TSEs) or prion diseases. It has been confirmed that the polymorphisms of prion protein gene (PRNP) at codons 136, 154, and 171 have strong relationship with scrapie in sheep. In the present study, nine polymorphisms of PRNP at codons 136, 154, and 171 and other six loci (at codons 101, 112, 127, 137, 138, and 152) were detected in 180 Chinese Hu sheep. All the alleles at codons 136, 154, and 171 have been identified and resulted in three new genotypes. The frequencies of predominant alleles were 85% (A136), 99.40% (R154), and 37.78% (Q171), respectively. The predominant haplotype ARQ has a relatively high frequency of 57.77%. The frequencies of dominant genotypes of ARR/ARQ and ARQ/ARQ were 30 and 26.67%, respectively. Three new found genotypes named ARQ/TRK, ARQ/TRR, and TRR/TRQ had the same lower frequencies (0.56%). The relationship of PRNP genotype with scrapie risk and litter size showed that the predominant genotypes are corresponded to the risk score of R(1) (1.67%), R(2) (32.22%), and R(3) (42.22%). Just at the first parity, the individuals with ARH/ARH genotype had significantly larger litter size than the mean value and those with ARQ/ARQ and ARR/ARQ genotypes. In short, this study provided preliminary information about alleles and genotypes of PRNP in Chinese Hu sheep. It could be concluded that Hu sheep has a low susceptibility to natural scrapie, and the predominant PRNP genotype at least has no significant effect on litter size.

Prion protein (PRNP) gene has been located at position q17 of chromosome 13 in cattle. The polymorphisms of PRNP gene might be associated with BSE susceptibility. In the present work, we investigated the polymorphisms of PRNP gene, including SNP in exon 3, 23-bp indel in promoter region, 12-bp indel in intron 1 in 2 Chinese indigenous cattle breeds of northeast China. Eighty-six animals from Yanbian (34) and Chinese Red Steppes (52) were genotyped at PRNP locus by analyzing genomic DNA. A total of 4 single nucleotide polymorphism (SNP) sites were revealed in the PRNP gene exon 3 of the 2 cattle breeds investigated. Three of these SNPs were non-synonymous mutations that resulted in the amino acid exchanges (K119N, S154N, and M177V), and one is silent nucleotide substitutions (A234G). The two amino acid mutations of S154N and M177V were detected only in Yanbian with a very low frequency (0.0147), and they appears to be absent in Chinese Red Steppes. The average gene heterozygosity (He), effective allele numbers (Ne), Shannon's information index (I) and polymorphism information content (PIC) were 0.3088, 1.5013, 0.3814 and 0.2000 in Yanbian, respectively, being relatively higher than that of Chinese Red Steppes (0.2885, 1.4985, 0.3462 and 0.1873, respectively). In 23-bp indel and 12-bp indel loci, three different genotypes were identified in both Yanbian and Chinese Red Steppes breeds. Based 23- and 12-bp indels, four haplotypes was constructed in the 2 Chinese cattle breeds, of which the 23-bp (-)/12-bp (-) was main haplotypes accounting for more than 50% of the total in both Yanbian and Chinese Red Steppes breeds. These results might be useful in understanding the genetic characteristics of PRNP gene in Chinese indigenous cattle breeds.

Susceptibility to natural scrapie in sheep is associated with polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene. To assess the risk of scrapie in sheep raised in China, DNA from 30 sheep of two breeds was isolated, amplified and sequenced for the PrP gene. The ovine PrP gene was found to be highly homogenous. The genotype associated with high susceptibility to scrapie (VRQ) was absent, whereas that associated with the resistance (ARR) was present in 6.7% of sheep examined. ARK was also rare (6.7%). ARQ that is associated with an intermediate susceptibility was the genotype observed in the most of sheep examined (86.6%). These data suggest that Chinese sheep of Mongolian sheep breed are susceptible to scrapie.

Scrapie is a fatal and infectious neurodegenerating disease. The polymorphism in the prion protein (PRNP) gene is linked to the development of clinical signs of scrapie. The most important polymorphism appears to be at codons at 136(V/A), 154(H/R), and 171(H/Q/R). In this study, we investigated the polymorphisms at these codons in 746 individuals among ten sheep breeds (i.e., ALeTai, BaShiBai, BaYinBuLuKe, Celehei, DuoLang, He Tian, Chinese Merino, German Merino, Texel, and Suffolk sheep) in Xinjiang in order to evaluate the relative susceptibility of sheep to scrapie. A total of 8 alleles (i.e., ARQ, ARR, ARH, ARK, VRQ, AHR, AHQ and AHH) were observed. The alleles ARQ and ARR were found in all of the breeds with the highest frequency for allele ARQ. Allele ARH was found in eight breeds except for Suffolk and German Merino, while the ARK was only identified in ALeTai, BaShiBai, BaYinBuLuKe, and DuoLang native sheeps. The alleles VRQ, AHR, AHQ and AHH were detected exclusively in Chinese Merino with extremely low frequencies. Moreover, the genotypes contained by the eight alleles were also determined subsequently. A total of thirteen genotypes, such as ARQ/ARQ, ARQ/ARK, ARR/ARR, ARH/ARH, ARQ/ARR, ARH/ARQ, ARH/ARR, ARK/ARK, ARH/ARK, ARQ/VRQ, ARQ/AHQ, ARQ/AHR and ARH/AHH were detected. The genotype ARQ/ARQ with moderate susceptibility was found with the highest frequency among the ten breeds, whereas the genotype ARR/ARR with highest resistance to scrapie was merely identified in BaYinBuLuKe, Celehei, Chinese Merino, Texel and German Merino sheep, which had very low frequencies. In addition, the genotype VRQ/ARQ with high susceptibility was first variant reported in Chinese Merino sheep. Our data, therefore, indicate that the general genetic resistance of dominating sheep breeds in Xinjiang to scrapie was considerably low.

Objective: To investigate epidemiological, clinical and genetic features of the first Chinese case of Creutzfeldt-Jakob disease (CJD ) with mutation of E200K in PRNP., Methods: The general epidemiological and clinical data were collected; CSF 14-3-3 protein was analyzed by Western blot; The PRNP was amplified by PCR and analyzed., Results: A missense mutation in codon 200 (E200K) of the PRNP was identified in this patient; CSF 14-3-3 protein was positive; sleep disturbance was the initial sign and the other symptoms gradually appeared, including memory loss, dizziness and ataxia., Conclusion: The CJD patient who was first reported in China has a missense mutation in codon 200 (E200K) of the PRNP, and the codon 129 is a methionine homozygous genotype.

Polymorphisms in four regions of the bovine prion protein gene (PRNP) confer susceptibility to bovine spongiform encephalopathy (BSE). These polymorphisms include a 23-bp insertion/deletion (indel) in the promoter region, a 12-bp indel in intron 1, an octapeptide repeat or 24-bp indel in the open reading frame, and a single nucleotide polymorphism (SNP) in the coding region. In this study, we investigated the frequency distributions of genotypes, alleles, and haplotypes at these indel sites in 349 native Chinese cattle and sequence variants in 50 samples. Our results showed that cattle in southern China have low frequencies of the 12-bp deletion allele and the 23-bp deletion / 12-bp deletion haplotype, which have been suggested to be relevant to BSE susceptibility. Interestingly, a significant difference was observed between BSE-affected cattle and healthy Chinese cattle in the 12-bp indel polymorphism. A total of 14 SNPs were discovered in the coding region of PRNP in Chinese cattle. Three of these SNPs were associated with amino acid changes (K3T, P54S, and S154N). The E211K substitution that was recently reported in the US atypical BSE case was not detected in this study.

Polymorphisms of the prion protein gene (Prnp), especially the amino acid residue alterations at codons 136, 154, and 174, in sheep have been found to be associated with susceptibility to scrapie disease. We investigated Prnp polymorphisms in three local sheep breeds in Inner Mongolia, China. Blood samples were collected from 46 Ujumqin, 34 Sunite, and 22 Mongolian sheep. The genetic DNA of blood samples was extracted, amplified and sequenced, and amino acid alignment was determined. Polymorphisms were detected at 8 codons, among which M157I, Q220H, and R223K have not been previously reported. The frequency of the amino acid residues ARQ/ARQ at codons 136, 154, and 171, respectively, which is associated with medium-high susceptibility to scrapie, was 74.5%, and the frequency of scrapie-resistant genotype ARR/ARR was 7.9%. The highly susceptible genotype VRQ/VRQ at these codons as not detected from the tested sheep. Of the three sheep breeds, Ujumqin sheep had the highest frequency (15.2%) of scrapie-resistant amino acid sequence, ARR/ARR at codons 136, 154, and 171, respectively, accounting for 87.5% sheep that carry these polymorphisms. Our findings are of special importance for both live sheep export and sheep breeding.

The polymorphism of the PRNP gene plays a key role in susceptibility to prion disease. Scrapie is a neurodegenerative disease affecting sheep and goats and belongs to the group of prion diseases. We isolated DNA from 333 goat samples representing the main local goat breeds in six provinces in China to identify PRNP polymorphisms and to determine whether these breeds were at risk for developing scrapie. Two novel amino acid polymorphisms (R211G and T219I) and a novel silent mutation at codon 125 as well as nine previously reported polymorphisms were observed. Twenty-eight alleles and forty-nine different genotypes were obtained. The codon 142M associated with resistance of goat scrapie was not found in this study. The codon 143R was relatively rare. The codon 222K, a potentially useful candidate site for selecting for scrapie resistance, was also rare in indigenous Chinese goats. These results could provide some useful data for assessing the risk of scrapie in Chinese indigenous goats.

Amino acid polymorphisms of the prion protein (PrP) gene (PRNP), particularly those occurring at codons 136, 154, and 171 have a significant influence on scrapie pathogenesis in many sheep breeds. 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. 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. Interestingly, the alanine (A)/V polymorphism at codon 136 was not observed in this study, all sheep being homozygous for A at this position. While the previously identified polymorphism of argine (R) or histidine (H) at codon 154 was detected, the H polymorphism was rare (2.25%). Four polymorphisms at codon 171 encoding glutamine (Q), R, H, or lysine (K) were detected. The predominant ARQ allele occurred at a high frequency of 77.48%, suggesting an increased risk of scrapie in Xinjiang Autonomous Region.

Prion diseases (transmissible spongiform encephalopathies, TSE), as a group of fatal neurodegenerative diseases, have affected humans and a variety of other mammals. Although no natural TSE have been documented in pigs, appropriate precautions need to be taken to prevent the iatrogenic spread of prion disease through pig-to-human xenotransplantation. Polymorphisms within the open reading frame (ORF) of the single-copy gene of prion protein (PRNP) are associated with susceptibility to scrapie in sheep and variant Creutzfeldt-Jacob disease in humans. We screened polymorphisms in the PRNP gene of 64 China Experimental Minipigs and Beijing Large White pigs. Our findings suggest that the porcine PRNP gene is highly homogenous. The amino acid sequences of the mature prion protein of all samples tested were identical. 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. We conclude that pigs raised under specific pathogen-free conditions, with the exclusion of rendered mammalian material for at least two generations, will have little risk of being infected with a TSE, and even less possibility of transmitting prion disease to humans through xenotransplantation.

Background: An amino acid polymorphism for Met to Val has been identified at PrP codon 129 from different human races. In this study,the characteristics of polymorphism of PRNP 129th amino acid in Han and Uighur Chinese have been investigated., Methods: Human DNAs were extracted from peripheral lymphocytes and PrP gene fragments were amplified with a specific PCR protocol. The distribution of 129th amino acid in PRNP was determined by a PCR-RFLP and the results were analyzed with software SAS for Windows 6.12., Results: The frequencies of the allele 129 Met and 129 Val were 97.0% and 3.0% in Han Chinese, whereas 91.4% and 8.6% in Uighur Chinese. The frequency of 129 M/M phenotypes in Han Chinese was significantly higher than that in Uighur Chinese (P=0.0490). Comparing the phenotype distributions of codon 129 of Han Chinese with that of Japanese and Caucasian, there was significant difference with Caucasian (P=0.0005),but there was no difference with Japanese (P=0.5040)., Conclusions: The polymorphism of 129th amino acid in PRNP of Han Chinese is similar to Japanese, but different from Uighur Chinese.

A point mutation at codon 210 (GTT to ATT) of the prion protein gene on chromosome 20 was found in a 48-year-old CJD-affected woman of a Chinese family. This affected woman had an early onset and long-duration form of CJD. Serial magnetic resonance image (MRI) analysis of this woman showed severe brain atrophy, prominent diffuse white matter degeneration, and subsequent mineralization of basal ganglia and thalamus. MR spectroscopy (1H) analysis elucidated the absence of peaks of choline, creatine and N-acetylaspartate. Using polymerase chain reaction and single-strand conformational polymorphism (PCR-SSCP) techniques, presymptomatic diagnosis of the second son of this woman showed that he has a similar codon mutation of prion gene as his mother.