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Genomic Variation between Genetic Lines of White Leghorns Differed in Resistance to Marek’s Disease

Qingmei Xie, Shuang Chang, Kunzhe Dong, John R Dunn, Jiuzhou Song and Huanmin Zhang

Genetic resistance to avian tumor virus-induced tumorigenesis and vaccine protective efficacy preventing such tumorigenicity are determined by multiple factors including host genetics, viral virulence, dose of challenge viruses, type of vaccine, vaccine dosage, and interval between vaccination and viral exposure time. Studies on human immune response to vaccination suggest host genetic variability has a strong effect and involves both genes within and outside of the major histocompatibility complex (MHC). Using chickens primarily from two highly inbred and specific pathogen free lines (6₃ and 7₂) sharing a common MHC (B*2) haplotype in challenge trials, we recently reported a striking difference in protective efficacy conveyed by HVT or CVI988/Rispens at either 500 PFU/bird or a commercial dosage. We also reported DNA methylation level that differs between the two lines of chickens at promoter regions of genes. Differential gene expression was also reported. This report documents Marek’s disease (MD) incidences of the two highly inbred lines and a series of Recombinant Congenic Strains (RCS) derived from the two lines, which were induced with a very virulent plus strain of MD virus, and illustrates genetic and epigenetic differences between the lines, which we anticipate, at least in part, are liable to the observed MD incidence and vaccine efficacy differences. The genetic and epigenetic mechanisms underlying both genetic resistances to MD and vaccine protective efficacy are complex. Therefore, continuous and systematic efforts on such study are warranted. A better understanding on genetic resistance to MD will empower the disease control through genetic or genomic selection, and a better understanding on the roles of host genetics in relation to immunogenicity in response to vaccination will serve as the touchstone for rational design and development of safer and more efficacious vaccines against infectious diseases.