Faculty of Veterinary Science, University of Sydney, Sydney, Australia.
PLoS One. 2012;7(6):e36955. doi: 10.1371/journal.pone.0036955. Epub 2012 Jun 6.
Devil facial tumour disease (DFTD) is a fatal contagious cancer that has decimated Tasmanian devil populations. The tumour has spread without invoking immune responses, possibly due to low levels of Major Histocompatibility Complex (MHC) diversity in Tasmanian devils. Animals from a region in north-western Tasmania have lower infection rates than those in the east of the state. This area is a genetic transition zone between sub-populations, with individuals from north-western Tasmania displaying greater diversity than eastern devils at MHC genes, primarily through MHC class I gene copy number variation. Here we test the hypothesis that animals that remain healthy and tumour free show predictable differences at MHC loci compared to animals that develop the disease.
METHODOLOGY/PRINCIPAL FINDINGS: We compared MHC class I sequences in 29 healthy and 22 diseased Tasmanian devils from West Pencil Pine, a population in north-western Tasmania exhibiting reduced disease impacts of DFTD. Amplified alleles were assigned to four loci, Saha-UA, Saha-UB, Saha-UC and Saha-UD based on recently obtained genomic sequence data. Copy number variation (caused by a deletion) at Saha-UA was confirmed using a PCR assay. No association between the frequency of this deletion and disease status was identified. All individuals had alleles at Saha-UD, disproving theories of disease susceptibility relating to copy number variation at this locus. Genetic variation between the two sub-groups (healthy and diseased) was also compared using eight MHC-linked microsatellite markers. No significant differences were identified in allele frequency, however differences were noted in the genotype frequencies of two microsatellites located near non-antigen presenting genes within the MHC.
CONCLUSIONS/SIGNIFICANCE: We did not find predictable differences in MHC class I copy number variation to account for differences in susceptibility to DFTD. Genotypic data was equivocal but indentified genomic areas for further study.
恶魔面部肿瘤病（DFTD）是一种致命的传染性癌症，已使塔斯马尼亚恶魔数量锐减。这种肿瘤在没有引发免疫反应的情况下扩散，可能是由于塔斯马尼亚恶魔的主要组织相容性复合体（MHC）多样性较低。来自塔斯马尼亚西北部一个地区的动物比该州东部的动物感染率低。该地区是亚种群之间的遗传过渡区，来自塔斯马尼亚西北部的个体在 MHC 基因上比东部恶魔表现出更大的多样性，主要是通过 MHC Ⅰ类基因拷贝数变异。在这里，我们检验了这样一个假设，即保持健康且无肿瘤的动物在 MHC 基因座上表现出可预测的差异，与患有该疾病的动物相比。
方法/主要发现：我们比较了来自塔斯马尼亚西北部 West Pencil Pine 的 29 只健康和 22 只患有恶魔面部肿瘤病的恶魔的 MHC Ⅰ类序列，该种群的 DFTD 疾病影响较小。根据最近获得的基因组序列数据，将扩增的等位基因分配到四个基因座 Saha-UA、Saha-UB、Saha-UC 和 Saha-UD 上。使用 PCR 测定法证实了 Saha-UA 处的拷贝数变异（由缺失引起）。未发现这种缺失与疾病状态之间存在关联。所有个体都有 Saha-UD 的等位基因，驳斥了与该基因座拷贝数变异相关的疾病易感性理论。还使用八个 MHC 连锁微卫星标记比较了两个亚组（健康和患病）之间的遗传变异。未发现等位基因频率存在显著差异，但在 MHC 内非抗原呈递基因附近的两个微卫星的基因型频率上注意到了差异。
结论/意义：我们没有发现 MHC Ⅰ类拷贝数变异的可预测差异可以解释对 DFTD 易感性的差异。基因型数据模棱两可，但确定了进一步研究的基因组区域。
