Animal & Avian Sciences

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    Characterization of Copy Number Variation’s Potential Role in Marek’s Disease
    (MDPI, 2017-05-09) Xu, Lingyang; He, Yanghua; Ding, Yi; Sun, Guirong; Carrillo, Jose Adrian; Li, Yaokun; Ghaly, Mona M.; Ma, Li; Zhang, Huanmin; Liu, George E.; Song, Jiuzhou
    Marek’s Disease (MD) is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. Chicken Lines 63 and 72, as well as their recombinant congenic strains (RCS) with varied susceptibility to MD, are ideal models to study the complex mechanisms of genetic resistance to MD. In this study, we investigated copy number variation (CNV) in these inbred chicken lines using the Affymetrix Axiom HD 600 K SNP genotyping array. We detected 393 CNV segments across all ten chicken lines, of which 12 CNVs were specifically identified in Line 72. We then assessed genetic structure based on CNV and observed markedly different patterns. Finally, we validated two deletion events in Line 72 and correlated them with genes expression using qPCR and RNA-seq, respectively. Our combined results indicated that these two CNV deletions were likely to contribute to MD susceptibility.
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    Identification and characterization of long intergenic noncoding RNAs associated with Marek's disease resistance in chicken
    (2013) Zhan, Fei; Song, Jiuzhou; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Marek's disease (MD) is a highly contagious lymphomatous disease of chicken caused by Marek's disease virus (MDV). MDV has steadily evolved toward increased resistance and virulence over the past decades. A promising strategy for MD prevention and control would be the enhancement of genetic resistance. This study aimed to investigate the roles of long intergenic noncoding RNAs (lincRNAs) in MD resistance and susceptibility in chickens. We reported more than 1000 lincRNA loci in chicken. Computational functional annotation suggested that lincRNAs were involved in a wide range of biological processes. Moreover, distinct lincRNA expression signatures were observed between MD resistance and susceptible chickens. Additionally, a candidate lincRNA termed linc-stab1 was identified and it may play an important role in MD immune response by regulating a nearby protein-coding gene STAB1. In summary, our results demonstrated that lincRNAs also play an important role in MD resistance and provide good candidates for hypothesis-driven functional studies.
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    Genome-Wide Analysis of Histone Modification Enrichments Induced by Marek's Disease Virus in Inbred Chicken Lines
    (2013) Mitra, Apratim; Song, Jiuzhou; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Covalent histone modifications constitute a complex network of transcriptional regulation involved in diverse biological processes ranging from stem cell differentiation to immune response. The advent of modern sequencing technologies enables one to query the locations of histone modifications across the genome in an efficient manner. However, inherent biases in the technology and diverse enrichment patterns complicate data analysis. Marek's disease (MD) is an acute, lymphoma-inducing disease of chickens with disease outcomes affected by multiple host and environmental factors. Inbred chicken lines 63 and 72 share the same major histocompatibility complex haplotype, but have contrasting responses to MD. This dissertation presents novel methods for analysis of genome-wide histone modification data and application of new and existing methods to the investigation of epigenetic effects of MD on these lines. First, we present WaveSeq, a novel algorithm for detection of significant enrichments in ChIP-Seq data. WaveSeq implements a distribution-free approach by combining the continuous wavelet transform with Monte Carlo sampling techniques for effective peak detection. WaveSeq outperformed existing tools particularly for diffuse histone modification peaks demonstrating that restrictive distributional assumptions are not necessary for accurate ChIP-Seq peak detection. Second, we investigated latent MD in thymus tissues by profiling H3K4me3 and H3K27me3 in infected and control birds from lines 63 and 72. Several genes associated with MD, e.g. MX1 and CTLA–4, along with those linked with human cancers, showed line-specific and condition-specific enrichments. One of the first studies of histone modifications in chickens, our work demonstrated that MD induced widespread epigenetic variations. Finally, we analyzed the temporal evolution of histone modifications at distinct phases of MD progression in the bursa of Fabricius. Genes involved in several important pathways, e.g. apoptosis and MAPK signaling, and various immune-related miRNAs showed differential histone modifications in the promoter region. Our results indicated heightened inflammation in the susceptible line during early cytolytic MD, while resistant birds showed recuperative symptoms during early MD and epigenetic silencing during latent infection. Thus, although further elucidation of underlying mechanisms is necessary, this work provided the first definitive evidence of the epigenetic effects of MD.
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    COMPARATIVE STUDY OF LIPOPROTEIN METABOLISM IN MAREK'S DISEASE SUSCEPTIBLE AND RESISTANT LINES
    (2010) Yuan, Ping; Song, Jiuzhou; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Marek's disease virus (MDV) infection causes atherosclerosis, and prior vaccination prevented the development of this disease. Two main strategies to resist Marek's disease (MD) have been demonstrated: vaccination and genetic resistance. However, little is known about the role of genetic resistance in the progression of MDV induced atherosclerosis. Atherosclerosis is primarily associated with lipoprotein metabolism. The purpose of this study was to investigate whether lipoprotein metabolisms are different in distinct MD susceptible and resistant chicken lines. Here, we studied different backgrounds of lipoprotein metabolism in the two lines and the changes of lipoprotein levels in response to MDV infection. The results showed that during chicken growth, the increase in total cholesterol was mostly due to the increasing (LDL+VLDL) in MD susceptible line, whereas it was mainly due to the elevating HDL in MD resistant line. These results suggested that different lipoprotein metabolisms exist in MD susceptible and resistant lines.