Selective Breeding for Disease-Resistant PRNP Variants to Manage Chronic Wasting Disease in Farmed Whitetail Deer.
Selective Breeding for Disease-Resistant PRNP Variants to Manage Chronic Wasting Disease in Farmed Whitetail Deer.
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DOI：
10.3390/genes12091396
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发表时间：
2021-09-10
期刊：
影响因子：
3.5
通讯作者：
Senior K
中科院分区：
文献类型：
--
作者：
Haley N;Donner R;Merrett K;Miller M;Senior K
慢性消耗性疾病（CWD）是一种致命的鹿科动物传染性海绵状脑病（TSE），由正常细胞朊病毒蛋白的错误折叠变体引起，与羊痒病密切相关。宿主朊病毒基因 PRNP 及其主要蛋白质结构的变异极大地影响了对特定朊病毒疾病的易感性，而预防瘙痒病感染的 PRNP 变异体的育种已导致北美和欧洲绵羊的这种疾病急剧下降。虽然已在鹿科动物中发现了耐药等位基因，但尚未发现完全预防 CWD 的 PRNP 变体。因此，传统上对养殖牛群疾病的控制依赖于检疫和减少数量。在 CWD 流行地区，减少私人牛群的数量变得难以证明其合理性，从而为就地控制该疾病提供了机会。我们为 CWD 高发区的养殖白尾鹿制定了选择性育种计划，重点是减少高度易感 PRNP 变异的频率并引入不易感变异的动物。通过使用新开发的引物，我们发现育种遵循可预测的孟德尔遗传，并且早期数据支持我们的项目在降低 CWD 患病率方面的效用。该项目代表了一种 CWD 管理的新颖方法，未来的努力将建立在这些发现的基础上。
Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy (TSE) of cervids caused by a misfolded variant of the normal cellular prion protein, and it is closely related to sheep scrapie. Variations in a host’s prion gene, PRNP, and its primary protein structure dramatically affect susceptibility to specific prion disorders, and breeding for PRNP variants that prevent scrapie infection has led to steep declines in the disease in North American and European sheep. While resistant alleles have been identified in cervids, a PRNP variant that completely prevents CWD has not yet been identified. Thus, control of the disease in farmed herds traditionally relies on quarantine and depopulation. In CWD-endemic areas, depopulation of private herds becomes challenging to justify, leading to opportunities to manage the disease in situ. We developed a selective breeding program for farmed white-tailed deer in a high-prevalence CWD-endemic area which focused on reducing frequencies of highly susceptible PRNP variants and introducing animals with less susceptible variants. With the use of newly developed primers, we found that breeding followed predictable Mendelian inheritance, and early data support our project’s utility in reducing CWD prevalence. This project represents a novel approach to CWD management, with future efforts building on these findings.
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