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<p>Chronic wasting disease (CWD) is a highly transmissible spongiform encephalopathy impacting cervids. Variations in the prion protein gene (<i>PRNP</i>), encoding the prion protein (PrP), influence disease progression and susceptibility. Protein sequence is a key determinant of PrP strains and their capacity for interspecies transmission. Sequencing <i>PRNP</i> in white-tailed deer has revealed non-synonymous polymorphisms impacting disease—c.285A &gt; C (Q95H) and c.286G &gt; A (G96S). Previous <i>PRNP</i> amplification protocols misclassified homozygous and heterozygous deer due to allelic dropout by a widely used forward primer. We resequenced 586 deer previously classified as homozygous using a redesigned primer (designated Ov-<i>PRNP</i>-F2) and found 128 heterozygotes. Subsequently, we sequenced additional CWD-positive and CWD-negative deer using Ov-<i>PRNP</i>-F2 to correct for dropout and then estimated PrP variant susceptibility and CWD risk using 778 CWD-positive and 3,070 CWD-negative deer from 22 Illinois counties, the largest <i>PRNP</i> sequence dataset to date. Animals encoding PrP variant combination C (96S) and F (95H) were the least susceptible to CWD (OR = 0.03, <i>p</i> &lt; 0.001) compared to deer encoding two copies of PrP variant A 95Q;96G. A novel finding is that deer encoding a single copy of PrP 95H were less susceptible to CWD compared to those with a single copy of PrP 96S (OR = 0.40, <i>p</i> &lt; 0.001). The results support using genotyping methods to map susceptibility to CWD across the landscape, focusing on PrP variant frequencies to improve CWD epidemiological risk models.</p>

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Odocoileus virginianus PRNP sequencing reveals AF (Q95G96/H95G96) advantage over AC (Q95G96/Q95S96) against chronic wasting disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月26日

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  • Evan W. London,
  • Alfred L. Roca,
  • Yasuko Ishida,
  • Tooba Latif,
  • Jan E. Novakofski,
  • Nohra E. Mateus-Pinilla

摘要

Chronic wasting disease (CWD) is a highly transmissible spongiform encephalopathy impacting cervids. Variations in the prion protein gene (PRNP), encoding the prion protein (PrP), influence disease progression and susceptibility. Protein sequence is a key determinant of PrP strains and their capacity for interspecies transmission. Sequencing PRNP in white-tailed deer has revealed non-synonymous polymorphisms impacting disease—c.285A > C (Q95H) and c.286G > A (G96S). Previous PRNP amplification protocols misclassified homozygous and heterozygous deer due to allelic dropout by a widely used forward primer. We resequenced 586 deer previously classified as homozygous using a redesigned primer (designated Ov-PRNP-F2) and found 128 heterozygotes. Subsequently, we sequenced additional CWD-positive and CWD-negative deer using Ov-PRNP-F2 to correct for dropout and then estimated PrP variant susceptibility and CWD risk using 778 CWD-positive and 3,070 CWD-negative deer from 22 Illinois counties, the largest PRNP sequence dataset to date. Animals encoding PrP variant combination C (96S) and F (95H) were the least susceptible to CWD (OR = 0.03, p < 0.001) compared to deer encoding two copies of PrP variant A 95Q;96G. A novel finding is that deer encoding a single copy of PrP 95H were less susceptible to CWD compared to those with a single copy of PrP 96S (OR = 0.40, p < 0.001). The results support using genotyping methods to map susceptibility to CWD across the landscape, focusing on PrP variant frequencies to improve CWD epidemiological risk models.