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Title: Quantitative evaluation of DNA methylation patterns for ALVEs and TVB genes in a neoplastic disease susceptible and resistant chicken model

item YUL, YING
item Zhang, Huanmin
item TIAN, FEI
item Bacon, Larry

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/28/2008
Publication Date: 3/5/2008
Citation: Yul, Y., Zhang, H.M., Tian, F., Bacon, L.D., Zhang, Y., Zhang, W., Song, J. 2008. Quantitative evaluation of DNA methylation patterns for ALVEs and TVB genes in a neoplastic disease susceptible and resistant chicken model. PLoS One. 3(3):e1731.

Interpretive Summary: Marek’s disease is a contagious disease that continues to pose a threat to the poultry industry. In addition to vaccination, genetic resistance to the disease has being sought to augment to disease control in chicken flocks. In this study, we identified novel DNA modification patterns known as DNA methylation patterns, which influence gene expression and will advance our understanding of genetic resistance to the disease. This finding may lead to better schemes for genetic improvement of disease resistance in chickens.

Technical Abstract: Chicken endogenous virus, ALVE (Avian Leukosis Virus subgroup E), is inherited as LTR (long terminal repeat) retrotransposons, which is negatively correlated with fitness and disease resistance, and any changes in DNA methylation pattern may thus contribute to the susceptibility to neoplastic disease. The relationship between ALVE methylation status and neoplastic disease in the chicken is undefined. Lines 63 and 72 White Leghorn inbred chickens at the ADOL have been respectively selected for resistance and susceptibility to tumors that are induced by avian viruses. In this study, the DNA methylation patterns of 3~6 CpG sites of the four conserved regions in ALVE, including one unique region in ALVE 1, the promoter region in the TVB (tumor virus receptor of ALV subgroup B) locus, were analyzed in the chicken lines 63 and 72 using Pyrosequencing methods in four tissues, i.e., liver, spleen, blood and hypothalamus. A significant CpG hypermethylation level was seen in line 72 in all four tissues, 91.86 ± 1.63% for ALVE region2 in blood, whereas the same region was hemimethylated (46.16 ± 2.56%) or hypomethylated (10.05 ± 3.41%) in line 63. CpG methylation contents of the ALVE regions were significantly lower in line 63 than in line 72 in all tissues (P <0.01) except the ALVE region 3/4 in the liver. RNA expressions of ALVE regions 2 and 3 (PPT-U3) were significantly higher in line 63 than in line 72 (P<0.01). The methylation levels of six recombinant congenic strains (RCSs) were much close to the parental line 63 in ALVE-region 2, which may imply an epigenetic pattern of ALVE-region 2 that has possibility to be a biomarker in resistant disease breeding. Methylation level of the promoter region in TVB gene was significantly different in blood (P<0.05) and hypothalamus (P<0.0001), respectively. Our data disclosed a hypermethylation pattern of ALVE that may be relevant for resistance against ALV in chickens.