USING THE GENOME TO UNDERSTAND IMMUNOGENETICS OF POULTRY
Location: Avian Disease and Oncology Laboratory
Title: Allele-specific expression analysis reveals CD79B has a cis-acting regulatory element that responds to Marek's disease virus infection in chickens
Submitted to: Poultry Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 8, 2011
Publication Date: June 17, 2011
Citation: Meydan, H., Yildiz, M.A., Dodgson, J.B., Cheng, H.H. 2011. Allele-specific expression analysis reveals CD79B has a cis-acting regulatory element that responds to Marek's disease virus infection in chicken. Poultry Science. 90(6):1206-1211.
Interpretive Summary: Marek’s disease (MD) is an economically-important disease of chickens caused by a pathogenic virus known as the Marek’s disease virus (MDV). Vaccines have controlled the problem but new emerging viral strains that result in disease outbreaks are being encountered more frequently, thus, additional control measures are needed such as genetic resistance. Despite the existence of the chicken genome assembly and an increasing number of powerful tools, the challenge still remains to identify the underlying causative genes that confer genetic resistance to MD. In this paper, we describe an example of how one can screen for transcriptional differences between alleles in a specific gene in response to MDV infection. When this occurs, this defines a genetic element and, thus, offer a simple solution for identify candidate genes for MD resistance with high confidence. This method has wide application in identifying all the genes that confer genetic resistance to MD as well as any other complex trait, which in turn should allow breeders to select superior animals more efficiently using genetic markers.
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 oncogenic, cell-associated 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. While previous work integrating QTL scans, transcript profiling, and MDV-chicken protein-protein interaction screens has revealed three MD resistance genes, 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 CD79B as 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 cSNP in CD79B and pyrosequencing to track the relative expression of each allele, we monitored ASE in uninfected and MDV-infected F1 progeny from intermatings of highly inbred chicken lines 63 (MD resistant) and 72 (MD susceptible). Upon screening three tissues (bursa, thymus, and spleen) at five different time points (1, 4, 7, 11 and 15 days post infection [dpi]), we observed that MDV infection alters the CD79B allelic ratios in bursa and thymus tissues at 4 and 15 dpi 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.