Identification of polymorphisms in the ovine <i>Shadow of prion protein</i> (<i>SPRN</i>) gene and assessment of their effect on promoter activity and susceptibility for classical scrapie

Lampo, Evelyne; Duchateau, Luc; Schepens, B.; Poucke, Mario Van; Saelens, Xavier; Erkens, Tim; Zeveren, Alex Van; Peelman, Luc

doi:10.1111/j.1365-2052.2009.01984.x

Cited by 18 publications

(22 citation statements)

References 45 publications

(43 reference statements)

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“…Using the Promoter Scan program, the forward strand spanning g.1176 to g.1426 was predicted as the putative promoter region for both the cattle and buffalo sequences. Conversely, Lampo et al had suggested the ovine SPRN promoter to be located in a more 5′ distant region, spanning g.739–1259 [26] (similar to bovine SPRN g.845–1407). Based upon this information, we first constructed the pGL3Basic reporter plasmid containing the fragment g.808–1691 to cover both possibilities.…”

Section: Resultsmentioning

confidence: 99%

Comparative Analysis of the Shadoo Gene between Cattle and Buffalo Reveals Significant Differences

Zhao

Liu

et al. 2012

PLoS ONE

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BackgroundWhile prions play a central role in the pathogenesis of transmissible spongiform encephalopathies, the biology of these proteins and the pathophysiology of these diseases remain largely unknown. Since no case of bovine spongiform encephalopathy (BSE) has ever been reported in buffalo despite their phylogenetic proximity to cattle, genetic differences may be driving the different susceptibilities of these two species to BSE. We thus hypothesized that differences in expression of the most recently identified member of the prion family or Shadoo (SPRN) gene may relate to these species-specific differences.Principal FindingsWe first analyzed and compared the polymorphisms of the SPRN gene (∼4.4 kb), including the putative promoter, coding and 3′ regions, and further verified the entire ORF and putative promoter. This yielded a total of 117 fixed differences, remarkably: 1) a 12-bp insertion/deletion polymorphism in the hydrophobic domain of the cattle but not buffalo gene, introducing a four amino acid expansion/contraction in a series of 5 tandem Ala/Gly-containing repeats; 2) two fixed missense mutations (102Ser→Gly and 119Thr→Ala), and three missense mutations (92Pro>Thr/Met, 122Thr>Ile and 139Arg>Trp) in the coding region presenting different (P<0.05) genotypic and allelic frequency distributions between cattle and buffalo; and, 3) functional luciferase-reporter experiments for the predicted promoter region, consistent with a significantly higher activity in buffalo than cattle. Supporting these findings, immunoblotting revealed higher relative expression levels of Sho protein in cerebrum from buffalo than from cattle. In addition, for cattle, highest Sho expression was detected in obex, as compared to cerebrum or cerebellum.SignificanceOur findings support Sho as a non-PrP specific marker for prion infections, with obex as the best tissue source for the detection of Sho in TSE rapid tests. Moreover, these discoveries may prove advantageous for further understanding the biology of prion diseases.

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Section: Resultsmentioning

confidence: 99%

Comparative Analysis of the Shadoo Gene between Cattle and Buffalo Reveals Significant Differences

Zhao

Liu

et al. 2012

PLoS ONE

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“…In humans, frame shift mutations induced by a single base pair insertion at codon 46 of the SPRN gene were found in two variant CJD patients 20 . In sheep, two alanine-deletion polymorphisms located in the hydrophobic region of the Sho protein showed significantly different genetic distributions between scrapie-affected animals and healthy animal 24 . In goats, an indel polymorphism (602_606insCTCCC) in the 3′ untranslated region (UTR) was related to scrapie susceptibility 20 .…”

Section: Introductionmentioning

confidence: 97%

Scrapie susceptibility-associated indel polymorphism of shadow of prion protein gene (SPRN) in Korean native black goats

Kim

Jeong

2019

Sci Rep

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Prion diseases in sheep and goats are called scrapie and belong to a group of transmissible spongiform encephalopathies (TSEs) caused by the abnormal misfolding of the prion protein encoded by the prion protein gene (PRNP). The shadow of the prion protein gene (SPRN) is the only prion gene family member that shows a protein expression profile similar to that of the PRNP gene in the central nervous system. In addition, genetic susceptibility of the SPRN gene has been reported in variant Creutzfeldt–Jakob disease (CJD), bovine spongiform encephalopathy (BSE) and scrapie. However, genetic studies of the SPRN gene have not been carried out in Korean native black goats. Here, we investigated the genotype and allele frequencies of SPRN polymorphisms in 213 Korean native black goats and compared these polymorphisms with those previously reported for scrapie-affected animals. We found a total of 6 polymorphisms including 1 nonsynonymous single nucleotide polymorphism (SNP) and 1 synonymous SNP in the open reading frame (ORF) region and 3 SNPs and 1 indel polymorphism (c.495_496insCTCCC) in the 3′ untranslated region (UTR) by direct DNA sequencing. A significant difference in the allele frequency of the c.495_496insCTCCC indel polymorphism was found between the Italian scrapie-affected goats and the Korean native black goats (P < 0.001). Furthermore, there was a significant difference in the allele frequencies of the c.495_496insCTCCC indel polymorphism between Italian healthy goats and Korean native black goats (P < 0.001). To evaluate the biological impact of the novel nonsynonymous SNP c.416G > A (Arg139Gln), we carried out PROVEAN analysis. PROVEAN predicted the SNP as ‘Neutral’ with a score of −0.297. To the best of our knowledge, this is the first genetic study of the SPRN gene in Korean native black goats.

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“…In humans, the null allele of the SPRN gene showed association with variant CJD 25 . In sheep, a polymorphism causing a deletion of two alanines was related to the susceptibility for scrapie 26 . In goats, an insertion/deletion polymorphism located on the 3′ UTR was associated with the susceptibility for scrapie 27 .…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of shadow of prion protein gene (SPRN) in Korean native cattle (Hanwoo) and Holstein cattle

Kim

Won

et al. 2020

Sci Rep

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Bovine spongiform encephalopathy (BSE) is a fatal infectious neurodegenerative disease caused by the accumulation of pathogenic prion protein (PrPSc) in the central nervous system (CNS), particularly in the brain. In a recent study, the shadow of prion protein (Sho), encoded by the shadow of prion protein (SPRN) gene, accelerates the progression of prion diseases, and a 12-bp insertion/deletion polymorphism in the coding region of the SPRN gene is associated with susceptibility to atypical BSE-affected Polish cattle. To date, the genetic study of the SPRN gene in Korean cattle has not been performed. In this study, we investigated the genotype and allele frequencies of SPRN polymorphisms in 235 Hanwoo and 212 Holstein cattle and analyzed the linkage disequilibrium (LD) and haplotypes of SPRN polymorphisms. In addition, we compared the distribution of the 12-bp insertion/deletion polymorphism between atypical BSE-diagnosed Polish cattle and Korean cattle to evaluate the susceptibility of atypical BSE. Furthermore, we estimated a deleterious effect of polymorphisms on the Sho protein using PROVEAN. We found a total of seven polymorphisms, including one novel single nucleotide polymorphism (SNP), c.231G>A. We also found significantly different distributions of genotype, allele and haplotype frequencies of seven polymorphisms between Hanwoo and Korean Holstein cattle. In addition, all polymorphisms showed strong LDs among the seven polymorphisms. Interestingly, Hanwoo cattle showed more potential susceptible distribution in the genotype and allele frequencies of the 12-bp insertion/deletion polymorphisms of the SPRN gene than Holstein cattle. Finally, using PROVEAN, we found one novel deleterious nonsynonymous SNP to Sho protein, c.110G>C (G37A). To the best of our knowledge, this is the first study of the SPRN gene in Korean cattle.

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Identification of polymorphisms in the ovine Shadow of prion protein (SPRN) gene and assessment of their effect on promoter activity and susceptibility for classical scrapie

Cited by 18 publications

References 45 publications

Comparative Analysis of the Shadoo Gene between Cattle and Buffalo Reveals Significant Differences

Comparative Analysis of the Shadoo Gene between Cattle and Buffalo Reveals Significant Differences

Scrapie susceptibility-associated indel polymorphism of shadow of prion protein gene (SPRN) in Korean native black goats

Polymorphisms of shadow of prion protein gene (SPRN) in Korean native cattle (Hanwoo) and Holstein cattle

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