Department of Animal Science, Ankara University, Ankara 06110, Turkey.
Poult Sci. 2011 Jun;90(6):1206-11. doi: 10.3382/ps.2010-01295.
Marek's disease (MD) is a T cell lymphoma disease of domestic chickens induced by the Marek's disease virus (MDV), a highly infectious and naturally oncogenic alphaherpesvirus. Enhancing genetic resistance to MD in poultry is an attractive method to augment MD vaccines, which protect against MD but do not prevent MDV replication and horizontal spread. Previous work integrating QTL scans, transcript profiling, and MDV-chicken protein-protein interaction screens revealed 3 MD resistance genes; however, a major challenge continues to be the identification of the other contributing genes. To aid in this search, we screened for allele-specific expression (ASE) in response to MDV infection, a simple and novel method for identifying polymorphic cis-acting regulatory elements, which may contain strong candidate genes with specific alleles that confer MD genetic resistance. In this initial study, we focused on immunoglobulin β (CD79B) because it plays a critical role in the immune response and, more important, is transcriptionally coupled with growth hormone (GH1), one of the previously identified MD resistance genes. Using a coding SNP in CD79B and pyrosequencing to track the relative expression of each allele, we monitored ASE in uninfected and MDV-infected F(1) progeny from reciprocal intermatings of highly inbred chicken lines 6(3) (MD resistant) and 7(2) (MD susceptible). Upon screening 3 tissues (bursa, thymus, and spleen) at 5 time points (1, 4, 7, 11, and 15 d postinfection), we observed that MDV infection alters the CD79B allelic ratios in bursa and thymus tissues at 4 and 15 d postinfection in both mating directions. Our results suggest that CD79B has a cis-acting regulatory element that responds to MDV infection and probably cooperates with GH1 in conferring genetic resistance to MD. This result helps validates the use of ASE screens to identify specific candidate genes for complex traits such as genetic resistance to MD.
马立克氏病（MD）是一种由马立克氏病病毒（MDV）引起的家禽 T 细胞淋巴瘤疾病，MDV 是一种高度传染性和天然致瘤的α疱疹病毒。增强家禽对 MD 的遗传抗性是增强 MD 疫苗的一种有吸引力的方法，MD 疫苗可以预防 MD，但不能阻止 MDV 的复制和水平传播。以前的工作将 QTL 扫描、转录谱分析和 MDV-鸡蛋白-蛋白相互作用筛选相结合，揭示了 3 个 MD 抗性基因；然而，一个主要的挑战仍然是确定其他贡献基因。为了帮助寻找这些基因，我们筛选了对 MDV 感染的等位基因特异性表达（ASE），这是一种识别多态性顺式作用调节元件的简单而新颖的方法，这些调节元件可能包含具有特定等位基因的强候选基因，这些特定等位基因赋予 MD 遗传抗性。在这项初步研究中，我们专注于免疫球蛋白β（CD79B），因为它在免疫反应中起着关键作用，更重要的是，它与先前确定的 MD 抗性基因之一生长激素 1（GH1）转录偶联。我们使用 CD79B 中的一个编码 SNP 和焦磷酸测序来跟踪每个等位基因的相对表达，监测来自高度近交鸡系 6(3)（MD 抗性）和 7(2)（MD 易感）相互交配的 F(1)后代在未感染和 MDV 感染后的 ASE。在筛查 5 个时间点（感染后 1、4、7、11 和 15 天）的 3 种组织（法氏囊、胸腺和脾脏）后，我们观察到 MDV 感染改变了 4 天和 15 天感染后两种交配方向的法氏囊和胸腺组织中的 CD79B 等位基因比例。我们的结果表明，CD79B 具有一个顺式作用调节元件，对 MDV 感染有反应，可能与 GH1 一起赋予 MD 的遗传抗性。这一结果有助于验证 ASE 筛选用于识别复杂性状（如 MD 遗传抗性）的特定候选基因的方法。
