Haase Bianca, Doherr Marcus G, Seuberlich Torsten, Drögemüller Cord, Dolf Gaudenz, Nicken Petra, Schiebel Katrin, Ziegler Ute, Groschup Martin H, Zurbriggen Andreas, Leeb Tosso
Institute of Genetics, Vetsuisse Faculty, University of Berne, Berne, Switzerland.
BMC Genet. 2007 Apr 16;8:15. doi: 10.1186/1471-2156-8-15.
Non-synonymous polymorphisms within the prion protein gene (PRNP) influence the susceptibility and incubation time for transmissible spongiform encephalopathies (TSE) in some species such as sheep and humans. In cattle, none of the known polymorphisms within the PRNP coding region has a major influence on susceptibility to bovine spongiform encephalopathy (BSE). Recently, however, we demonstrated an association between susceptibility to BSE and a 23 bp insertion/deletion (indel) polymorphism and a 12 bp indel polymorphism within the putative PRNP promoter region using 43 German BSE cases and 48 German control cattle. The objective of this study was to extend this work by including a larger number of BSE cases and control cattle of German and Swiss origin.
Allele, genotype and haplotype frequencies of the two indel polymorphisms were determined in 449 BSE cattle and 431 unaffected cattle from Switzerland and Germany including all 43 German BSE and 16 German control animals from the original study. When breeds with similar allele and genotype distributions were compared, the 23 bp indel polymorphism again showed a significant association with susceptibility to BSE. However, some additional breed-specific allele and genotype distributions were identified, mainly related to the Brown breeds.
Our study corroborated earlier findings that polymorphisms in the PRNP promoter region have an influence on susceptibility to BSE. However, breed-specific differences exist that need to be accounted for when analyzing such data.
朊病毒蛋白基因（PRNP）内的非同义多态性会影响某些物种（如绵羊和人类）对传染性海绵状脑病（TSE）的易感性和潜伏期。在牛中，PRNP编码区内已知的多态性均未对牛海绵状脑病（BSE）的易感性产生重大影响。然而，最近我们利用43例德国BSE病例和48头德国对照牛，证明了PRNP假定启动子区域内的一个23 bp插入/缺失（indel）多态性和一个12 bp indel多态性与BSE易感性之间存在关联。本研究的目的是通过纳入更多德国和瑞士来源的BSE病例和对照牛来扩展这项工作。
在来自瑞士和德国的449头BSE牛和431头未受影响的牛中确定了这两种indel多态性的等位基因、基因型和单倍型频率，其中包括原始研究中的所有43例德国BSE病例和16头德国对照动物。当比较等位基因和基因型分布相似的品种时，23 bp indel多态性再次显示出与BSE易感性有显著关联。然而，还发现了一些额外的品种特异性等位基因和基因型分布，主要与棕色品种有关。
我们的研究证实了早期的发现，即PRNP启动子区域的多态性会影响对BSE的易感性。然而，在分析此类数据时，存在需要考虑的品种特异性差异。
