ADRA2C is also subjected to epigenetic modulation and the domestic phenotype in White leghorn is by being significantly hypermethylated compared to wild type Red Junglefowl. Cysteine methylation on CpG-islands modulates gene expression and can be inherited suggesting that domestication is not limited to only selection on genetic variance but could also operate on epigenetic signatures. We hypothesized that the selective sweep on chromosome 4 adjacent to the ADRA2C locus is associated with regulatory effects on ADRA2C expression, which could TRV130 hydrochloride affect behavior in stressful situations. Gene expression and receptor density was evaluated in the adrenals and in the brain in RJF and WL chickens. Because these Doripenem Hydrate strains differ in behavior and physiology, and because of the difficulties associating a behavioral difference with a candidate gene between heterogeneous groups we used an F10 advanced intercross line between RJF and WL homozygous for alternative ADRA2C alleles for behavior and fecundity studies. Using this method, we could study the effect of the domestic genotype compared to a mosaic genomic background that has resulted from 9 generations of accumulating recombination between the two chicken strains. On chromosome 4 in the chicken genome there is a strong selective sweep showing signatures of selection in White leghorn chickens. This area is void of genes except for ADRA2C, an autoregulatory transmembrane receptor of epinephrine and norepinephrine release in the CNS and the adrenal glands directly linked to the fight-and flight response and fearfulness. The promoter region is hypermethylated in WL further highlighting it as an important gene in domestication. The present study shows that despite the highly suggestive initial premises, ADRA2C is probably not involved in the domestication of stress-related phenotypes in WL chickens. No differences were found in expression levels in adrenals and hypothalamus, nor the amount of ADRA2C in relevant brain areas. It should be noted that the gene is downstream and outside of the sweep region, so any effect related to this gene would rely on, for example, an enhancer present within the sweep.