Genome-Wide Assessment of Copy Number Variation in Two Chicken Lines with Different Susceptibility to Marek's Disease Using Next Generation Sequencing

Copy number variation (CNV) is a major source of genetic and phenotypic variation and accumulating evidences suggest that CNV is responsible for a number of genetic disorders and the susceptibility to infectious diseases. Here we present a genome-wide assessment of CNV in two highly inbred chicken lines (6₃ and 7₂ from ADOL) with different susceptibility to Marek’s disease (MD). Three chickens from each line were randomly selected and sequenced to an average depth of 20. On average, 1,600 CNVs with much higher resolution than previously studies were detected in each chicken. We hypothesized that the resistance or susceptibility to MD is genetically controlled by some common CNVs within the population, and merged the CNVs into 3,242 CNV regions (CNVRs), and only retained CNVRs shared by all individuals within each line for further analysis. Finally, we found 140 and 147 line-specific CNVRs in resistant (6₃) and susceptible (7₂) lines, respectively. These CNVRs overlapped 122 unique ensemble genes. No line-specific CNVRs were found on GGA16, a micro-chromosome bearing major histocompatibility complex (MHC), which is a major loci influencing the susceptibility to MD. Integrating extensive QTL mapping studies conducted in the same chicken lines, we were able to narrow down our results to 4 novel promising genes, GRIK2, IRF2, KIF26A and PLA2G1B. Human homologs of these genes are either associated with human disorder or involved in cell proliferation, tumor genesis and progression. We suggest that these genes are potential candidates related to the susceptibility to MD and worth further study.