Department of Forest and Wildlife Ecology, University of Wisconsin-Madison, Madison, WI 53706, United States.
Infect Genet Evol. 2009 Dec;9(6):1329-35. doi: 10.1016/j.meegid.2009.08.010. Epub 2009 Aug 31.
The genetic basis of susceptibility to chronic wasting disease (CWD) in free-ranging cervids is of great interest. Association studies of disease susceptibility in free-ranging populations, however, face considerable challenges including: the need for large sample sizes when disease is rare, animals of unknown pedigree create a risk of spurious results due to population admixture, and the inability to control disease exposure or dose. We used an innovative matched case-control design and conditional logistic regression to evaluate associations between polymorphisms of complement C1q and prion protein (Prnp) genes and CWD infection in white-tailed deer from the CWD endemic area in south-central Wisconsin. To reduce problems due to admixture or disease-risk confounding, we used neutral genetic (microsatellite) data to identify closely related CWD-positive (n=68) and CWD-negative (n=91) female deer to serve as matched cases and controls. Cases and controls were also matched on factors (sex, location, age) previously demonstrated to affect CWD infection risk. For Prnp, deer with at least one Serine (S) at amino acid 96 were significantly less likely to be CWD-positive relative to deer homozygous for Glycine (G). This is the first characterization of genes associated with the complement system in white-tailed deer. No tests for association between any C1q polymorphism and CWD infection were significant at p<0.05. After controlling for Prnp, we found weak support for an elevated risk of CWD infection in deer with at least one Glycine (G) at amino acid 56 of the C1qC gene. While we documented numerous amino acid polymorphisms in C1q genes none appear to be strongly associated with CWD susceptibility.
慢性消瘦病（CWD）在自由放养的鹿群中的易感性的遗传基础是非常有趣的。然而，对自由放养种群中疾病易感性的关联研究面临着相当大的挑战，包括：当疾病罕见时需要大量的样本量，由于种群混合，未知谱系的动物会产生虚假结果的风险，以及无法控制疾病暴露或剂量。我们使用了一种创新的匹配病例对照设计和条件逻辑回归来评估补体 C1q 和朊病毒蛋白（Prnp）基因的多态性与威斯康星州中南部 CWD 流行地区白尾鹿的 CWD 感染之间的关联。为了减少由于混合或疾病风险混杂引起的问题，我们使用中性遗传（微卫星）数据来识别密切相关的 CWD 阳性（n=68）和 CWD 阴性（n=91）母鹿作为匹配的病例和对照。病例和对照还根据先前证明会影响 CWD 感染风险的因素（性别、位置、年龄）进行匹配。对于 Prnp，与甘氨酸（G）纯合的鹿相比，至少有一个丝氨酸（S）在氨基酸 96 处的鹿患 CWD 的可能性明显降低。这是首次对白尾鹿补体系统相关基因进行特征描述。没有任何 C1q 多态性与 CWD 感染之间关联的测试在 p<0.05 时具有显著意义。在控制 Prnp 后，我们发现 C1qC 基因中至少有一个氨基酸 56 处为甘氨酸（G）的鹿感染 CWD 的风险略有升高。虽然我们记录了 C1q 基因中的许多氨基酸多态性，但似乎没有一种与 CWD 易感性有很强的关联。
