scholarly journals Ribosomal protein SA and its pseudogenes in ruminants: an extremely conserved gene family

2013 ◽  
Vol 58 (No. 2) ◽  
pp. 79-90 ◽  
Author(s):  
A. Van den Broeke ◽  
M. Van Poucke ◽  
A. Van Zeveren ◽  
L.J. Peelman
Keyword(s):  
Gene Family ◽  
Ribosomal Protein ◽  
In Silico ◽  
Prion Diseases ◽  
Bovine Genome ◽  
Laminin Receptor ◽  
Transmissible Spongiform Encephalopathies ◽  
Coding Region ◽  
Structural Mutations ◽  
Flanking Regions

The ribosomal protein SA (RPSA), also known as 37-kDa laminin receptor precursor/67-kDa laminin receptor (LRP/LR), has been identified as a multifunctional protein, playing an important role in multiple pathologies like cancer and prion diseases. Since RPSA is involved in the binding and internalization of the prion protein, mutations in the ovine RPSA gene, influencing the RPSA-PrP<sup>C</sup>/PrP<sup>Sc </sup>binding, can potentially play a part in the resistance to prion diseases. Our goal was to further characterize the complex RPSA gene family and to detect structural mutations which can play a role in this disease. In a prior study, 11 ovine pseudogenes were detected experimentally. As the whole genome shotgun ovine genome became accessible, an in silico genome-wide screening was performed and 37 new pseudogenes (36 processed and one semi-processed pseudogene) were detected, bringing the total to 48 ovine RPSA pseudogenes. Additionally, the complete bovine genome was screened in silico and 56 pseudogenes were identified. Once these sequences were known, it was possible to analyze the presence of mutations in the coding sequence and exon-flanking regions of the ovine functional full-length RPSA gene without the interference of pseudogenic sequences. Nineteen mutations were found: one in the 5&rsquo; UTR, a silent one in the coding region, and seventeen in the exon-flanking regions, including an interesting mutation in the SNORA62 gene, localized in intron 4 of RPSA, leading to potential ribosomal defects. Structural mutations of the RPSA gene can be ruled out to play a role in transmissible spongiform encephalopathies but regulatory mutations still can have an effect on these diseases.

In Silico Analysis of HSP70 Gene Family in Bovine Genome

2020 ◽  
Author(s):  
Kabita Tripathy ◽  
Monika Sodhi ◽  
R. S. Kataria ◽  
Meenu Chopra ◽  
Manishi Mukesh
Keyword(s):  
Gene Family ◽  
In Silico ◽  
Bovine Genome ◽  
In Silico Analysis ◽  
Hsp70 Gene ◽  
Silico Analysis

Characterization of the porcine multicopy ribosomal protein SA/37-kDa laminin receptor gene family

Gene ◽  
2007 ◽  
Vol 395 (1-2) ◽  
pp. 135-143 ◽  
Author(s):  
Christoph Knorr ◽  
Christian Beuermann ◽  
Julia Beck ◽  
Bertram Brenig
Keyword(s):  
Gene Family ◽  
Ribosomal Protein ◽  
Receptor Gene ◽  
Laminin Receptor ◽  
Receptor Gene Family

scholarly journals Backbone NMR assignments of the C-terminal domain of the human prion protein and its disease‐associated T183A variant

2021 ◽  
Vol 15 (1) ◽  
pp. 193-196
Author(s):  
Máximo Sanz-Hernández ◽  
Alfonso De Simone
Keyword(s):  
Prion Protein ◽  
Nmr Assignments ◽  
Chemical Shifts ◽  
Prion Diseases ◽  
Random Coil ◽  
Transmissible Spongiform Encephalopathies ◽  
Globular Domain ◽  
Structural Elements ◽  
Spongiform Encephalopathies ◽  
Human Prion Protein

AbstractTransmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders associated with the misfolding and aggregation of the human prion protein (huPrP). Despite efforts into investigating the process of huPrP aggregation, the mechanisms triggering its misfolding remain elusive. A number of TSE-associated mutations of huPrP have been identified, but their role at the onset and progression of prion diseases is unclear. Here we report the NMR assignments of the C-terminal globular domain of the wild type huPrP and the pathological mutant T183A. The differences in chemical shifts between the two variants reveal conformational alterations in some structural elements of the mutant, whereas the analyses of secondary shifts and random coil index provide indications on the putative mechanisms of misfolding of T183A huPrP.

scholarly journals The 67-kDa laminin receptor originated from a ribosomal protein that acquired a dual function during evolution

1998 ◽  
Vol 15 (8) ◽  
pp. 1017-1025 ◽  
Author(s):  
E. Ardini ◽  
G. Pesole ◽  
E. Tagliabue ◽  
A. Magnifico ◽  
V. Castronovo ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Laminin Receptor ◽  
Dual Function

scholarly journals Human prion diseases: surgical lessons learned from iatrogenic prion transmission

2016 ◽  
Vol 41 (1) ◽  
pp. E10 ◽  
Author(s):  
David J. Bonda ◽  
Sunil Manjila ◽  
Prachi Mehndiratta ◽  
Fahd Khan ◽  
Benjamin R. Miller ◽  
...  
Keyword(s):  
Prion Disease ◽  
Disease Transmission ◽  
Prion Diseases ◽  
The United States ◽  
Lessons Learned ◽  
World Health ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Prion Transmission ◽  
Iatrogenic Transmission

The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood “infectious protein” has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments.

scholarly journals Prion Disease Blood Test Using Immunoprecipitation and Improved Quaking-Induced Conversion

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Christina D. Orrú ◽  
Jason M. Wilham ◽  
Lynne D. Raymond ◽  
Franziska Kuhn ◽  
Björn Schroeder ◽  
...  
Keyword(s):  
Real Time ◽  
Blood Test ◽  
Prion Diseases ◽  
Proteinase K ◽  
Transmissible Spongiform Encephalopathies ◽  
Serum Samples ◽  
Spongiform Encephalopathies ◽  
Jakob Disease

ABSTRACT A key challenge in managing transmissible spongiform encephalopathies (TSEs) or prion diseases in medicine, agriculture, and wildlife biology is the development of practical tests for prions that are at or below infectious levels. Of particular interest are tests capable of detecting prions in blood components such as plasma, but blood typically has extremely low prion concentrations and contains inhibitors of the most sensitive prion tests. One of the latter tests is quaking-induced conversion (QuIC), which can be as sensitive as in vivo bioassays, but much more rapid, higher throughput, and less expensive. Now we have integrated antibody 15B3-based immunoprecipitation with QuIC reactions to increase sensitivity and isolate prions from inhibitors such as those in plasma samples. Coupling of immunoprecipitation and an improved real-time QuIC reaction dramatically enhanced detection of variant Creutzfeldt-Jakob disease (vCJD) brain tissue diluted into human plasma. Dilutions of 1014-fold, containing ~2 attogram (ag) per ml of proteinase K-resistant prion protein, were readily detected, indicating ~10,000-fold greater sensitivity for vCJD brain than has previously been reported. We also discriminated between plasma and serum samples from scrapie-infected and uninfected hamsters, even in early preclinical stages. This combined assay, which we call “enhanced QuIC” (eQuIC), markedly improves prospects for routine detection of low levels of prions in tissues, fluids, or environmental samples. IMPORTANCE Transmissible spongiform encephalopathies (TSEs) are largely untreatable and are difficult to diagnose definitively prior to irreversible clinical decline or death. The transmissibility of TSEs within and between species highlights the need for practical tests for even the smallest amounts of infectivity. A few sufficiently sensitive in vitro methods have been reported, but most have major limitations that would preclude their use in routine diagnostic or screening applications. Our new assay improves the outlook for such critical applications. We focused initially on blood plasma because a practical blood test for prions would be especially valuable for TSE diagnostics and risk reduction. Variant Creutzfeldt-Jakob disease (vCJD) in particular has been transmitted between humans via blood transfusions. Enhanced real-time quaking-induced conversion (eRTQ) provides by far the most sensitive detection of vCJD to date. The 15B3 antibody binds prions of multiple species, suggesting that our assay may be useful for clinical and fundamental studies of a variety of TSEs of humans and animals.

scholarly journals Genomic Basis of Aromatase Excess Syndrome: Recombination- and Replication-Mediated Rearrangements Leading to CYP19A1 Overexpression

2013 ◽  
Vol 98 (12) ◽  
pp. E2013-E2021 ◽  
Author(s):  
Maki Fukami ◽  
Takayoshi Tsuchiya ◽  
Heike Vollbach ◽  
Kristy A. Brown ◽  
Shuji Abe ◽  
...  
Keyword(s):  
Gc Content ◽  
Replication Timing ◽  
Nonhomologous End Joining ◽  
Coding Region ◽  
End Joining ◽  
Clinical Consequences ◽  
Underlying Mechanisms ◽  
Nonallelic Homologous Recombination ◽  
Genomic Disorders ◽  
Flanking Regions

Context: Genomic rearrangements at 15q21 have been shown to cause overexpression of CYP19A1 and resultant aromatase excess syndrome (AEXS). However, mutation spectrum, clinical consequences, and underlying mechanisms of these rearrangements remain to be elucidated. Objective: The aim of the study was to clarify such unsolved matters. Design, Setting, and Methods: We characterized six new rearrangements and investigated clinical outcome and local genomic environments of these rearrangements and of three previously reported duplications/deletions. Results: Novel rearrangements included simple duplication involving exons 1–10 of CYP19A1 and simple and complex rearrangements that presumably generated chimeric genes consisting of the coding region of CYP19A1 and promoter-associated exons of neighboring genes. Clinical severities were primarily determined by the copy number of CYP19A1 and the property of the fused promoters. Sequences at the fusion junctions suggested nonallelic homologous recombination, nonhomologous end-joining, and replication-based errors as the underlying mechanisms. The breakpoint-flanking regions were not enriched with GC content, palindromes, noncanonical DNA structures, or known rearrangement-associated motifs. The rearrangements resided in early-replicating segments. Conclusions: These results indicate that AEXS is caused by duplications involving CYP19A1 and simple and complex rearrangements that presumably lead to the usage of cryptic promoters of several neighboring genes. Our data support the notion that phenotypes depend on the dosage of CYP19A1 and the characteristics of the fused promoters. Furthermore, we show that the rearrangements in AEXS are generated by both recombination- and replication-mediated mechanisms, independent of the known rearrangement-inducing DNA features or late-replication timing. Thus, AEXS represents a unique model for human genomic disorders.

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