AUTHOR=Maceachern Sean , Muir William M., Crosby Seth D., Cheng Hans 

TITLE=Genome-Wide Identification and Quantification of cis- and trans-Regulated Genes Responding to Marek’s Disease Virus Infection via Analysis of Allele-Specific Expression

JOURNAL=Frontiers in Genetics

VOLUME=2

YEAR=2012

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2011.00113

DOI=10.3389/fgene.2011.00113

ISSN=1664-8021

ABSTRACT=<p>Marek’s disease (MD) is a commercially important neoplastic disease of chickens caused by Marek’s disease virus (MDV), a naturally occurring oncogenic alphaherpesvirus. Selecting for increased genetic resistance to MD is a control strategy that can augment vaccinal control measures. To identify high-confidence candidate MD resistance genes, we conducted a genome-wide screen for allele-specific expression (ASE) amongst F<sub>1</sub> progeny of two inbred chicken lines that differ substantially in MD resistance. High throughput sequencing was initially used to profile transcriptomes from pools of uninfected and infected individuals at 4 days post-infection to identify any genes showing ASE in response to MDV infection. RNA sequencing identified 22,655 single nucleotide polymorphisms (SNPs) of which 5,360 in 3,773 genes exhibited significant allelic imbalance. Illumina GoldenGate assays were subsequently used to quantify regulatory variation controlled at the gene (<italic>cis</italic>) and elsewhere in the genome (<italic>trans</italic>) by examining differences in expression between F<sub>1</sub> individuals and artificial F<sub>1</sub> RNA pools over six time periods in 1,536 of the most significant SNPs identified by RNA sequencing. Allelic imbalance as a result of <italic>cis</italic>-regulatory changes was confirmed in 861 of the 1,233 GoldenGate assays successfully examined. Furthermore we have identified seven genes that display <italic>trans</italic>-regulation only in infected animals and ∼500 SNP that show a complex interaction between <italic>cis</italic>- and <italic>trans</italic>-regulatory changes. Our results indicate ASE analyses are a powerful approach to identify regulatory variation responsible for differences in transcript abundance in genes underlying complex traits. And the genes with SNPs exhibiting ASE provide a strong foundation to further investigate the causative polymorphisms and genetic mechanisms for MD resistance. Finally, the methods used here for identifying specific genes and SNPs have practical implications for applying marker-assisted selection to complex traits that are difficult to measure in agricultural species, when expression differences are expected to control a portion of the phenotypic variance.</p>