Johnson Chad, Johnson Jody, Vanderloo Joshua P, Keane Delwyn, Aiken Judd M, McKenzie Debbie
Department of Animal Health and Biomedical Sciences, University of Wisconsin, 1656 Linden Drive, Madison, WI 53706, USA.
Wisconsin Veterinary Diagnostic Laboratory, Madison, WI 53705, USA.
J Gen Virol. 2006 Jul;87(Pt 7):2109-2114. doi: 10.1099/vir.0.81615-0.
The primary sequence of the prion protein affects susceptibility to transmissible spongiform encephalopathies, or prion diseases, in mice, sheep and humans. The Prnp gene sequence of free-ranging, Wisconsin white-tailed deer was determined and the Prnp genotypes of chronic wasting disease (CWD)-positive and CWD-negative deer were compared. Six amino acid changes were identified, two of which were located in pseudogenes. Two alleles, a Q-->K polymorphism at codon 226 and a single octapeptide repeat insertion into the pseudogene, have not been reported previously. The predominant alleles--wild-type (Q95, G96 and Q226) and a G96S polymorphism--comprised almost 98% of the Prnp alleles in the Wisconsin white-tailed deer population. Comparison of the allelic frequencies in the CWD-positive and CWD-negative deer suggested that G96S and a Q95H polymorphism were linked to a reduced susceptibility to CWD. The G96S allele did not, however, provide complete resistance, as a CWD-positive G96S/G96S deer was identified. The G96S allele was also linked to slower progression of the disease in CWD-positive deer based on the deposition of PrP(CWD) in the obex region of the medulla oblongata. Although the reduced susceptibility of deer with at least one copy of the Q95H or G96S allele is insufficient to serve as a genetic barrier, the presence of these alleles may modulate the impact of CWD on white-tailed deer populations.
朊病毒蛋白的一级序列会影响小鼠、绵羊和人类对传染性海绵状脑病（即朊病毒病）的易感性。测定了威斯康星州自由放养的白尾鹿的Prnp基因序列，并比较了慢性消耗病（CWD）阳性和CWD阴性鹿的Prnp基因型。鉴定出六个氨基酸变化，其中两个位于假基因中。此前尚未报道过两个等位基因，即密码子226处的Q→K多态性和假基因中的单个八肽重复插入。主要等位基因——野生型（Q95、G96和Q226）和G96S多态性——占威斯康星州白尾鹿种群中Prnp等位基因的近98%。比较CWD阳性和CWD阴性鹿的等位基因频率表明，G96S和Q95H多态性与对CWD的易感性降低有关。然而，G96S等位基因并未提供完全抗性，因为鉴定出了一只CWD阳性的G96S/G96S鹿。基于延髓闩部区域PrP（CWD）的沉积，G96S等位基因还与CWD阳性鹿疾病进展较慢有关。尽管至少有一个Q95H或G96S等位基因拷贝的鹿易感性降低不足以构成遗传屏障，但这些等位基因的存在可能会调节CWD对白尾鹿种群的影响。
