Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie.
Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie.
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DOI：
10.1101/gad.8.8.959
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发表时间：
1994-04
影响因子：
10.5
通讯作者：
D. Westaway;V. Zuliani;C. Cooper;M. Da Costa;S. Neuman;A L Jenny;L. Detwiler;S. B. Prusiner
中科院分区：
文献类型：
--
作者：
D. Westaway;V. Zuliani;C. Cooper;M. Da Costa;S. Neuman;A L Jenny;L. Detwiler;S. B. Prusiner
自然的羊瘙痒病被认为是一种隐性性状，也是一种受宿主基因座调控的传染病。为了解决这个难题，我们确定了绵羊朊蛋白（PrP）基因的结构，该基因包含三个外显子，延伸超过20 kb的DNA。在美国，86.4%的痒病病例发生在萨福克羊中，在该品种中，49 +/- 6%（+/- S.D.，n = 69）携带一个或多个编码Arg（R）-171的PrP等位基因。4只羊瘙痒症感染羊为野生型PrP开放阅读框纯合子，编码替代Gln（Q）-171等位基因。对其他病例的分析显示，所有病例均为Q/Q-171纯合子（n = 31），PrP基因型与易感性无关的概率为0.000004。这些数据表明，Q-171密码子的纯合性是必要的，但不足以发展的自然痒病，隐性表现的回声报告，并平行过度代表人类克雅氏病的PRNP密码子129纯合子。尽管啮齿动物实验性瘙痒病取得了实质性进展，但疾病在羊群中的发生和传播仍然是个谜。密码子171基因型和易感性之间的关系的评价可能有助于确定自然痒病的分子基础。
Natural scrapie has been viewed both as a recessive trait and as a contagious disease modulated by a host locus. To address this conundrum, we determined the structure of the sheep prion protein (PrP) gene, which contains three exons and extends over 20 kb of DNA. In the United States 86.4% of scrapie cases occur in Suffolk sheep, and within this breed 49 +/- 6% (+/- S.D., n = 69) of healthy animals carry one or more PrP alleles encoding Arg (R)-171. Four scrapie-affected sheep were homozygous for wild-type PrP open reading frames encoding the alternative Gln (Q)-171 allele. Analysis of additional cases revealed that all were Q/Q-171 homozygotes (n = 31), yielding a probability of 0.000004 that PrP genotype is unrelated to susceptibility. These data imply that homozygosity for Q-171 codons is necessary but not sufficient for the development of natural scrapie, echo reports of recessive manifestation, and parallel over-representation of PRNP codon 129 homozygotes in Creutzfeldt-Jakob disease of humans. Whereas progress has been substantial regarding experimental scrapie in rodents, the occurrence and spread of disease in flocks of sheep has remained enigmatic. Appreciation of the relationship between codon 171 genotype and susceptibility may help define the molecular basis of natural scrapie.