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Title: Chicks and single-nucleotide polymorphisms: an entree into identifying genes conferring disease resistance in chicken

Author
item Cheng, Hans
item MACEACHERN, SEAN - Cobb-Vantress, Inc
item SUBRAMANIAM, SUGA - Michigan State University
item MUIR, WILLIAM - Purdue University

Submitted to: Animal Production Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/11/2012
Publication Date: 1/13/2012
Citation: Cheng, H.H., Maceachern, S., Subramaniam, S., Muir, W.M. 2012. Chicks and single-nucleotide polymorphisms: an entree into identifying genes conferring disease resistance in chicken. Animal Production Science. 52(3). Available: http://dx.doi.org/10.1071/AN11099.

Interpretive Summary: Marek’s disease is the most serious chronic disease due to the constant presence of the Marek’s disease virus in poultry farms. This disease is largely controlled by vaccines and rearing practices but due to spontaneous and unpredictable disease outbreaks, alternative control measures are needed such as enhanced genetic resistance. Thus, efforts have been conducted to identify genes and genetic markers that could be used to select for superior disease resistant birds. In this review, we summarize the current state of our efforts, which incorporate ultra high throughput DNA sequencers to great advantage. These new strategies and tools have identified a large number of potential genes that could be used for poultry breeding.

Technical Abstract: Marek's disease (MD) is one of the most serious chronic infectious disease threats to the U.S. poultry industry. Selecting for increased genetic resistance to MD is a control strategy that can augment current vaccinal control measures. Although our previous efforts integrating various genomic screens successfully identified three resistance genes, the main limitation was mapping precision, which hindered our ability to identify and further evaluate high confidence candidate genes. Towards identifying the remaining genes of this complex trait, we incorporated three additional approaches made substantially more powerful through next generation sequencing and exploit the growing importance of expression variation. First, we screened for allele-specific expression (ASE) in response to Marek’s disease virus (MDV) infection, which when allelic imbalance was identified, is sufficient to indicate a cis-acting element for a specific gene. Second, sequencing of genomic regions enriched by chromatin immunoprecipitation (ChIP) combined with transcript profiling identified motifs bound and genes directly regulated by MDV Meq, a bZIP transcription factor and the viral oncogene. Finally, analysis of genomic sequences from two experimental lines divergently selected for MD genetic resistance allowed for regions under selection as well as potential causative polymorphisms. These new combined approaches have resulted in a large number of high confidence genes conferring MD resistance reflecting the multigenic basis of this trait and expanding our biological knowledge, and corresponding SNPs that can be directly evaluated for their genetic contribution towards disease resistance.