Abstract
Abnormal neurotransmitter concentration is one of the factors that affect the health status, behavioral personality, and welfare level of animals, but the genetic basis of the abnormality is still largely unknown. The objective of this study is to identify putative genomic loci associated with neurotransmitter concentration in cattle. We measured serotonin (5HT), dopamine (DA), cortisol, glutamate (Glu), and ACTH concentrations in blood serum using double-antibody sandwich ELISA in 30 Brahman cattle and 127 Yunling cattle. Interestingly, we found that ACTH concentration was positively correlated with body weight, cannon circumference, and hip width (P < 0.05). Genome-wide association study (GWAS) was performed with mixed linear models using autosomal SNPs derived from the whole-genome sequence. We identified five, five, two, three, and five suggestive loci associated with 5HT, DA, cortisol, Glu, and ACTH concentration, respectively. These 20 associated loci implicated 18 candidate genes. For Glu concentration, the most significant association locus was assigned to MCHR1, a G-coupled receptor that could modulate glutamate release. For dopamine concentration, a very strong association locus was located in the intron of SLC18A2, which is a critical mediator of dopamine dynamics. However, for ACTH concentration, a very strong association locus was assigned to HTR1F, a G protein-coupled receptor that can influence the release of ACTH. Other candidate genes of interest identified for neurotransmitter concentration were PRMT6, GADD45A, PCCA, ANGPT1, ACCS, LOC100336971, TNR, GSDMA, CNTN3, CARMIL1, CDKAL1, RBFOX1, PCDH15, and LGALS12. Our findings will provide targets for the genetic improvement of neurotransmitter-related traits in domestic cattle and basic materials for studying the mechanism of neurotransmitter synthesis, release, and transport in human and animals.
Highlights
Neurotransmitters are endogenous chemical substances that act as chemical messengers during synaptic transmission
We implemented Genome-wide association study (GWAS) to identify the genomic loci explaining the phenotypic variance in neurotransmitter concentrations in blood serum using the whole-genome sequence
Five, two, three, and five suggestive loci associated with 5HT, DA, cortisol, Glu, and ACTH, respectively, suggesting that neurotransmitter concentration in blood serum is polygenetically controlled
Summary
Neurotransmitters are endogenous chemical substances that act as chemical messengers during synaptic transmission. Investigation of neurotransmitter content in blood is helpful for understanding the mechanism of psychiatric and neurodegenerative disease in human. Neurotransmitter content in blood was often acted as an indicator correlating with physiological state, temperamental difference, and welfare level. Previous study has proved that minor corral changes and the adoption of good handling practices in Nellore cows can reduce the cortisol release of individuals (Lima et al, 2018). The revelation of genetic mechanisms underlying plasma neurotransmitter concentration will provide a genetic method to select individuals with a stable physiological state and moderate temperament to raise the welfare level and improve production efficiency in cattle, there are few studies that establish the links between neurotransmitter concentration and genetic variants
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