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Title: SCREENING FOR CANDIDATE GENES THAT CONFER MAREK'S DISEASE RESISTANCE BY COMBINING TWO-HYBRID ASSAYS AND QTL LINKAGE ANALYSIS

Author
item Liu, Hsiao Ching
item Niikura, Masahiro
item Cheng, Hans

Submitted to: Plant and Animal Genome Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 1/11/2003
Publication Date: 1/12/2003
Citation: Liu, H., Niikura, M., Cheng, H.H. 2003. Screening for candidate genes that confer marek's disease resistance by combining two-hybrid assays and QTL linkage analysis [abstract]. Plant and Animal Genome Conference Proceedings. p. 108.

Interpretive Summary:

Technical Abstract: The long-term research goal of our group is to identify and characterize the genetic determinants of resistance to Marek's disease (MD), a herpesvirus-induced T-cell cancer of chickens, caused by the Marek's disease virus (MDV). Our strategy is to apply various genomic approaches to gain an understanding of the molecular basis of MDV oncogenesis and host genetic resistance. For example, we integrated the yeast two-hybid screen, which detects protein-protein interactions, with QTL linkage analysis, which identifies genome regions that influence a trait. Essentially, our hypothesis is chicken proteins that interact with MDV proteins are potentially involved in the pathways of immune response or pathogenesis. And by mapping the corresponding genes, we would efficiently test if interacting proteins are associated with disease resistance. Our recent publication (PNAS 98:9203) that demonstrates (1) growth hormone (GH) interacts with MDV SORF2 and (2) GH confers MD resistance, validates this integrative strategy. Given our success, we have expanded our screen using the E. coli two-hybrid system with 20 more selected MDV genes. Thus far, we have identified many virus-host interactions with 6 being confirmed by in vitro binding assay. More importantly, at least one lies in a previously identified QTL region suggesting that it is a positional candidate gene. Interestingly, several of the host proteins are involved in antigen presentation, which suggests that MDV, like other herpesviruses, actively suppresses the immune response. These initial results demonstrate that there is great potential in a systematic proteomics-genomic approach for MD, as well as many other systems.