Chicks and single-nucleotide polymorphisms: an entrée into identifying genes conferring disease resistance in chicken

Abstract

Abstract. Marek's disease (MD) is one of the most serious chronic infectious disease threats to the poultry industry worldwide. Selecting for increased genetic resistance to MD is a control strategy that can augment current vaccinal control measures. Although our previous efforts integrating various genomic screens successfully identified three resistance genes, the main limitation was mapping precision, which hindered our ability to identify and further evaluate highconfidence candidate genes. Towards identifying the remaining genes of this complex trait, we incorporated three additional approaches made substantially more powerful through next-generation sequencing and that exploit the growing importance of expression variation. First, we screened for allele-specific expression (ASE) in response to Marek's disease virus (MDV) infection, which, when allelic imbalance was identified, is sufficient to indicate a cisacting element for a specific gene. Second, sequencing of genomic regions enriched by chromatin immunoprecipitation (ChIP) combined with transcript profiling identified motifs bound and genes directly regulated by MDV Meq, a bZIP transcription factor and the viral oncogene. Finally, analysis of genomic sequences from two experimental lines divergently selected for MD genetic resistance allowed inference about regions under selection as well as potential causative polymorphisms. These new combined approaches have resulted in a large number of high-confidence genes conferring MD resistance reflecting the multigenic basis of this trait, which expands our biological knowledge and provides corresponding single-nucleotide polymorhpisms (SNPs) that can be directly evaluated for their genetic contribution towards disease resistance.

Genome-wide identification of copy number variations between two chicken lines that differ in genetic resistance to Marek’s disease

“…With modern statistical and genomic tools, Li et al [ 8 ] reported two loci associated with MD resistance through genome-wide association study (GWAS). However, the resolution limits of these strategies make it difficult to identify the underlying causative genes, and the variants only explain a small proportion of total genetic variation [ 9 ], leaving a large part of variation unexplained [ 10 ]. More recently, Cheng et al [ 11 ] found that SNPs in allele-specific expression (ASE) genes captures more than 83 % of the additive genetic variation of MD resistance, demonstrating that the most of the ASE genes are strong candidates of underlying genes of MD resistance.…”