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Abstract：
Chronic wasting disease (CWD) is caused by prions, infectious proteinaceous particles, PrPCWD. We sequenced the PRNP gene of 2,899 white-tailed deer (WTD) from Illinois and southern Wisconsin, finding 38 haplotypes. Haplotypes A, B, D, E, G and 9 others encoded Q95G96S100N103A123Q226, designated \'PrP variant A.\' Haplotype C and 4 other haplotypes encoded PrP \'variant C\' (Q95S96S100N103A123Q226). Haplotype F and two other haplotypes encoded PrP \'variant F\' (H95G96S100N103A123Q226). The association of CWD with encoded PrP variants was examined in 2,537 tested WTD from counties with CWD. Relative to PrP variant A, CWD susceptibility was lower in deer with PrP variant C (OR = 0.26, p < 0.001), and even lower in deer with PrP variant F (OR = 0.10, p < 0.0001). Susceptibility to CWD was highest in deer with both chromosomes encoding PrP variant A, lower with one copy encoding PrP variant A (OR = 0.25, p < 0.0001) and lowest in deer without PrP variant A (OR = 0.07, p < 0.0001). There appeared to be incomplete dominance for haplotypes encoding PrP variant C in reducing CWD susceptibility. Deer with both chromosomes encoding PrP variant F (FF) or one encoding PrP variant C and the other F (CF) were all CWD negative. Our results suggest that an increased population frequency of PrP variants C or F and a reduced frequency of PrP variant A may reduce the risk of CWD infection. Understanding the population and geographic distribution of PRNP polymorphisms may be a useful tool in CWD management.
摘要：
慢性消耗性疾病（CWD）是由朊病毒引起的，感染性蛋白质颗粒，PrPCWD。我们对来自伊利诺伊州和威斯康星州南部的2,899只白尾鹿（WTD）的PRNP基因进行了测序，发现38个单倍型。单倍型A,B,D,E,G和其他9个编码Q95G96S100N103A123Q226，命名为\'PrP变体A.\'单倍型C和4个其他单倍型编码PrP\'变体C'（Q95S96S100N103A123Q226）。单倍型F和另外两种单倍型编码PrP'变体F'(H95G96S100N103A123Q226)。在来自患有CWD的县的2,537个测试的WTD中检查了CWD与编码的PrP变体的关联。相对于PrP变体A，具有PrP变体C的鹿的CWD易感性较低（OR=0.26，p<0.001），在具有PrP变体F的鹿中甚至更低（OR=0.10，p<0.0001）。对CWD的易感性在两个编码PrP变体A的染色体中最高，一个编码PrP变体A的拷贝较低（OR=0.25，p<0.0001），而无PrP变体A的鹿最低（OR=0.07，p<0.0001）。编码PrP变体C的单倍型在降低CWD易感性方面似乎存在不完全的优势。具有编码PrP变体F(FF)或一个编码PrP变体C和另一个F(CF)的两条染色体的鹿都是CWD阴性的。我们的结果表明，PrP变体C或F的种群频率增加以及PrP变体A的频率降低可能会降低CWD感染的风险。了解PRNP多态性的种群和地理分布可能是CWD管理的有用工具。
