Genetics, Physical Anthropology and Animal Physiology Department, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao, Spain.
Immunogenetics. 2010 Feb;62(2):75-83. doi: 10.1007/s00251-009-0419-2. Epub 2010 Jan 5.
Ovine pulmonary adenocarcinoma (OPA) and Maedi-Visna (Maedi) are two chronic respiratory diseases of retroviral origin which occur worldwide. It is known that different host genetic factors influence the outcome of viral infections. To determine if variation in the Mhc-DRB1 gene was associated with progression to these ovine diseases, sheep lungs with and without OPA and Maedi lesions were collected. A sequence-based method was applied and 40 different alleles were detected in the sample analysed. In the allele-by-allele association analysis, allele DRB10325 had a significant association with susceptibility to Maedi (P = 0.045). For OPA, DRB10143 and DRB10323 were significantly associated with susceptibility (P = 0.024 and P = 0.029), and allele DRB10702 was significantly associated with resistance (P = 0.012). Based on these results, the Mhc-DRB1 alleles were classified by effect in three categories-susceptible (S), resistant (R) and neutral (N)-and animals were reassigned the genotypes as S/S, S/R, S/N, R/R, R/N and N/N. In a second analysis, penalised logistic regression models including a flock effect were run. In Maedi, significant association was detected for the N/S heterozygote (P = 0.0007), but not for the S/S homozygote, probably as a result of the low number of S/S animals. In OPA, association was detected for both the S/S and R/R homozygotes (P = 0.005 and P = 0.047). This allele grouping method may be applied in association studies with highly variable genes. This is the first study demonstrating significant associations between sheep Mhc-DRB1 alleles and susceptibility to OPA and Maedi. Therefore, both diseases are suitable candidates for more comprehensive genetic studies.
绵羊肺腺瘤病（OPA）和梅迪-维斯纳病（Maedi）是两种由逆转录病毒引起的慢性呼吸道疾病，在世界范围内都有发生。已知不同的宿主遗传因素会影响病毒感染的结果。为了确定 MHC-DRB1 基因的变异是否与这些绵羊疾病的进展有关，收集了有和无 OPA 和 Maedi 病变的绵羊肺。应用基于序列的方法，在分析的样本中检测到 40 个不同的等位基因。在等位基因-等位基因关联分析中，等位基因 DRB10325 与 Maedi 的易感性显著相关（P = 0.045）。对于 OPA，DRB10143 和 DRB10323 与易感性显著相关（P = 0.024 和 P = 0.029），等位基因 DRB10702 与抗性显著相关（P = 0.012）。基于这些结果，Mhc-DRB1 等位基因根据效应分为三类-易感（S）、抗性（R）和中性（N）-并将动物的基因型重新分配为 S/S、S/R、S/N、R/R、R/N 和 N/N。在第二项分析中，运行了包括羊群效应的惩罚逻辑回归模型。在 Maedi 中，检测到 N/S 杂合子的显著关联（P = 0.0007），但 S/S 纯合子的关联不显著，可能是由于 S/S 动物数量较少所致。在 OPA 中，S/S 和 R/R 纯合子都检测到了关联（P = 0.005 和 P = 0.047）。这种等位基因分组方法可应用于高度变异基因的关联研究。这是第一项证明绵羊 MHC-DRB1 等位基因与 OPA 和 Maedi 易感性之间存在显著关联的研究。因此，这两种疾病都是更全面遗传研究的合适候选对象。
