Ascites syndrome (AS) is a metabolic disorder that mainly occurs at later ages of meat-type chickens. Despite many research, there is no consensus about the origin of this syndrome. Our main purpose were to investigate the syndrome using both phenotypic and RNA-Seq data to elucidate the most causative factors predisposing the birds to AS. Phenotypic data analysis showed that AS indicator traits (AITs) were moderate to high heritable. Inexistence of consistent direct genetic correlation between AITs and growth related traits, indicated that neither faster growth rate nor heavier body weight is the most causative factor affecting the susceptibility of broilers to AS. However, respiratory capacity was revealed to be the most probable factor predisposing the birds to AS, as both lung weight and lung percentage were negatively correlated with AITs. Transcriptomic data analysis revealed 125 differentially expressed genes (DEGs) between the ascitic and healthy groups. Up-regulated genes in ascitic group enriched mainly in gas transport biological process, while down-regulated genes involved in defense response to bacteria, biological adhesion, cell adhesion, killing of cells of another organism and cell division. Genetic association of the DEGs with human cardiovascular diseases suggested excessive heart problems of the ascitic chicks. Heart is, probably, the first tissue suffering from the incompetence of small respiratory system of the AS-susceptible chickens. In other word, tissue hypoxia, that causes free radicals to concentrate in heart cells, may be the commencement of events that finally result to heart failure, suffocation and death of chicks due to the AS.

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