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Published on: August 8, 2017
Novel polymorphisms and functional characterization of the prion protein gene in sparrows (Passer montanus)
Chau-Giang Truong1,2, Da-In Choi1,2, Byung-Hoon Jeong1,2
1Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk, Republic of Korea.
Background:
Misfolding of the prion protein (PrP) into an aberrant conformation causes prion diseases in several mammalian species; however, no prion infections have been documented in birds so far. The prion protein gene (PRNP) has been extensively studied in mammals, but little is known about PRNP polymorphisms in avian species and their potential roles in resistance to prion pathogenesis. However, the genetic variation of the sparrow PRNP gene remains largely uncharacterized.
Materials And Methods:
To better understand the genetic diversity of PRNP gene in sparrows, we sequenced the coding region from genomic DNA of 44 individuals. We analyzed the genetic characteristics of the sparrow PRNP gene, including genotype, allele, and haplotype distributions, as well as linkage disequilibrium (LD) among single nucleotide polymorphisms (SNPs) and insertion/deletion (indel) variants. The functional effects of the identified polymorphisms were predicted using multiple in silico tools, including PolyPhen-2, SIFT, AMYCO, SODA, and MutPred-Indel. In addition, the structural impact of non-synonymous substitutions was assessed by structural modeling tools, and the amino acid sequences of the hexapeptide tandem repeat were compared across avian species.
Results:
A total of 24 polymorphisms were identified in the sparrow PRNP gene, including 9 non-synonymous substitutions and 3 indels. Among these, the A121V substitution was predicted to have the most detrimental effect, causing pronounced structural perturbation and increased amyloid propensity of sparrow PrP. The L5P and W105R substitutions also showed potentially deleterious impacts on protein stability. Among the indel polymorphisms, c.190_207delAACCCGGGCTACCCCCAC and c.243_244insAACCCCGGCTACCCCCAC were predicted to reduce solubility, whereas c.225_226insAACCCGGGCTACCCCCAC increased solubility. Furthermore, sparrow PrP exhibited a comparable length to that of quail, with both species containing eight hexapeptide repeat units.
Conclusion:
As far as we know, this study represents the first report of PRNP genetic polymorphisms in sparrows, providing baseline data for future studies on avian prion resistance.
Insights
This study reveals genetic variations in the sparrow prion protein gene (PRNP). Identified polymorphisms, including A121V, may influence avian resistance to prion diseases.
Area of Science:
- Genomics
- Molecular Biology
- Veterinary Science
Background:
- Prion diseases stem from misfolded prion protein (PrP) in mammals.
- Avian prion infections are undocumented, but the genetic basis for resistance is unknown.
- Sparrow PRNP gene variation remains largely uncharacterized.
Purpose of the Study:
- To investigate the genetic diversity of the sparrow PRNP gene.
- To identify PRNP polymorphisms in sparrows and predict their functional impacts.
- To establish baseline data for avian prion resistance research.
Main Methods:
- Sequencing the PRNP coding region from 44 sparrows.
- Analyzing genotype, allele, haplotype distributions, and linkage disequilibrium.
- Utilizing in silico tools (PolyPhen-2, SIFT, etc.) and structural modeling to predict functional effects of polymorphisms.
Main Results:
- Identified 24 polymorphisms in sparrow PRNP, including 9 non-synonymous substitutions and 3 indels.
- The A121V substitution showed the most detrimental predicted effect on PrP structure and amyloid propensity.
- Specific indel polymorphisms impacted sparrow PrP solubility; sparrow PrP hexapeptide repeat length is comparable to quail.
Conclusions:
- This is the first report of PRNP genetic polymorphisms in sparrows.
- Findings provide crucial baseline data for future avian prion resistance studies.
- Understanding PRNP variation may elucidate mechanisms of prion disease resistance in birds.
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