关键词: Doppel PRND SNP polymorphism prion prion-like protein gene rabbit

来  源:   DOI:10.3389/fvets.2024.1388339   PDF(Pubmed)

Abstract:
UNASSIGNED: Natural cases of prion disease have not been reported in rabbits, and prior attempts to identify a prion conversion agent have been unsuccessful. However, recent applications of prion seed amplifying experimental techniques have sparked renewed interest in the potential susceptibility of rabbits to prion disease infections. Among several factors related to prion disease, polymorphisms within the prion-like protein gene (PRND), a member of the prion protein family, have been reported as significantly associated with disease susceptibility in various species. Therefore, our study aimed to investigate polymorphisms in the PRND gene of rabbits and analyze their genetic characteristics.
UNASSIGNED: Genomic DNA was extracted from 207 rabbit samples to investigate leporine PRND polymorphisms. Subsequently, amplicon sequencing targeting the coding region of the leporine PRND gene was conducted. Additionally, linkage disequilibrium (LD) analysis was employed to assess the connection within and between loci. The impact of non-synonymous single nucleotide polymorphisms (SNPs) on the Doppel protein was evaluated using PolyPhen-2.
UNASSIGNED: We found nine novel SNPs in the leporine PRND gene: c.18A > G, c.76G > C, c.128C > T, c.146C > T, c.315A > G, c.488G > A, c.525G > C, c.544G > A, and c.579A > G. Notably, seven of these PRND SNPs, excluding c.525G > C and c.579A > G, exhibited strong LD values exceeding 0.3. In addition, LD analysis confirmed a robust link between PRNP SNP c.234C > T and PRND SNPs at c.525G > C and c.579A > G. Furthermore, according to PolyPhen-2 and SIFT analyses, the four non-synonymous SNPs were predicted to have deleterious effects on the function or structure of the Doppel protein. However, PANTHER and Missense3D did not indicate such effects.
UNASSIGNED: In this paper, we have identified novel SNPs in the rabbit PRND gene and predicted their potential detrimental effects on protein function or structure through four non-synonymous SNPs. Additionally, we observed a genetic linkage between SNPs in the PRND and PRNP genes. These findings may provide insights into understanding the characteristics of rabbits as partially resistant species. To the best of our knowledge, this study is the first to genetically characterize PRND SNPs in rabbits.
摘要:
在兔子中没有报道过朊病毒病的自然病例,并且先前鉴定朊病毒转化剂的尝试都没有成功。然而,朊病毒种子扩增实验技术的最新应用引起了人们对兔对朊病毒病感染的潜在易感性的新兴趣。在与朊病毒疾病相关的几个因素中,朊病毒样蛋白基因(PRND)内的多态性,病毒蛋白家族的一员,据报道,在各种物种中与疾病易感性显着相关。因此,本研究旨在调查家兔PRND基因的多态性并分析其遗传特征。
从207个兔样本中提取基因组DNA以研究草孔素PRND多态性。随后,进行靶向leporinePRND基因编码区的扩增子测序。此外,连锁不平衡(LD)分析用于评估基因座内部和基因座之间的连接。使用PolyPhen-2评估了非同义单核苷酸多态性(SNP)对Doppel蛋白的影响。
我们在leporinePRND基因中发现了9个新的SNP:c.18a>G,c.76G>C,c.128C>T,c.146C>T,c.315A>G,c.488G>A,c.525G>C,c.544G>A,和c.579A>G值得注意的是,其中七个PRNDSNP,不包括c.525G>C和c.579A>G,表现出超过0.3的强LD值。此外,LD分析证实了PRNPSNPc.234C>T和PRNDSNP在c.525G>C和c.579A>G之间的牢固联系。此外,根据PolyPhen-2和SIFT分析,预测四个非同义SNP对Doppel蛋白的功能或结构具有有害影响。然而,PANTHER和Missense3D没有显示这种影响。
在本文中,我们在兔PRND基因中发现了新的SNP,并通过4个非同义SNP预测了它们对蛋白质功能或结构的潜在有害影响.此外,我们观察到PRND和PRNP基因中SNP之间的遗传连锁。这些发现可能为了解兔子作为部分抗性物种的特征提供了见解。据我们所知,这项研究是首次在家兔中对PRNDSNP进行遗传表征。
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