Department of Veterinary Pathobiology, Texas A&M University, College Station, TX 77843, USA.
Texas Parks and Wildlife Department, Austin, TX 78744, USA.
G3 (Bethesda). 2022 Jul 6;12(7). doi: 10.1093/g3journal/jkac109.
Despite implementation of enhanced management practices, chronic wasting disease in US white-tailed deer (Odocoileus virginianus) continues to expand geographically. Herein, we perform the largest genome-wide association analysis to date for chronic wasting disease (n = 412 chronic wasting disease-positive; n = 758 chronic wasting disease-nondetect) using a custom Affymetrix Axiom single-nucleotide polymorphism array (n = 121,010 single-nucleotide polymorphisms), and confirm that differential susceptibility to chronic wasting disease is a highly heritable (h2= 0.611 ± 0.056) polygenic trait in farmed US white-tailed deer, but with greater trait complexity than previously appreciated. We also confirm PRNP codon 96 (G96S) as having the largest-effects on risk (P ≤ 3.19E-08; phenotypic variance explained ≥ 0.025) across 3 US regions (Northeast, Midwest, South). However, 20 chronic wasting disease-positive white-tailed deer possessing codon 96SS genotypes were also observed, including one that was lymph node and obex positive. Beyond PRNP, we also detected 23 significant single-nucleotide polymorphisms (P-value ≤ 5E-05) implicating ≥24 positional candidate genes; many of which have been directly implicated in Parkinson's, Alzheimer's and prion diseases. Genotype-by-environment interaction genome-wide association analysis revealed a single-nucleotide polymorphism in the lysosomal enzyme gene ARSB as having the most significant regional heterogeneity of effects on chronic wasting disease (P ≤ 3.20E-06); with increasing copy number of the minor allele increasing susceptibility to chronic wasting disease in the Northeast and Midwest; but with opposite effects in the South. In addition to ARSB, 38 significant genotype-by-environment single-nucleotide polymorphisms (P-value ≤ 5E-05) were also detected, thereby implicating ≥ 36 positional candidate genes; the majority of which have also been associated with aspects of Parkinson's, Alzheimer's, and prion diseases.
尽管实施了强化管理措施，美国白尾鹿（Odocoileus virginianus）的慢性消瘦病仍在继续扩大地理范围。在此，我们利用定制的 Affymetrix Axiom 单核苷酸多态性芯片（n = 121,010 个单核苷酸多态性）对慢性消瘦病（n = 412 例慢性消瘦病阳性；n = 758 例慢性消瘦病未检出）进行了迄今为止最大的全基因组关联分析，并确认慢性消瘦病的不同易感性是一个高度可遗传的（h2= 0.611 ± 0.056）多基因特征，在养殖的美国白尾鹿中，但比以前认为的更复杂。我们还确认 PRNP 密码子 96（G96S）对风险的影响最大（P ≤ 3.19E-08；表型方差解释≥ 0.025），跨越 3 个美国地区（东北部、中西部、南部）。然而，也观察到 20 头携带密码子 96SS 基因型的慢性消瘦病阳性白尾鹿，其中包括一头淋巴结和 obex 阳性的白尾鹿。除了 PRNP，我们还检测到 23 个显著的单核苷酸多态性（P 值 ≤ 5E-05），涉及 ≥24 个位置候选基因；其中许多基因直接与帕金森病、阿尔茨海默病和朊病毒病有关。基因型-环境互作全基因组关联分析显示，溶酶体酶基因 ARSB 中的一个单核苷酸多态性对慢性消瘦病的影响在区域上具有最显著的异质性（P ≤ 3.20E-06）；在东北部和中西部，次要等位基因的拷贝数增加会增加对慢性消瘦病的易感性；但在南部则相反。除了 ARSB，还检测到 38 个显著的基因型-环境单核苷酸多态性（P 值 ≤ 5E-05），涉及 ≥36 个位置候选基因；其中大多数也与帕金森病、阿尔茨海默病和朊病毒病的某些方面有关。
