A Comprehensive Systematic Review Coupled with an Interacting Network Analysis Identified Candidate Genes and Biological Pathways Related to Bovine Temperament

Abstract

Comprehension of the genetic basis of temperament has been improved by recent advances in the identification of genes and genetic variants. However, due to the complexity of the temperament traits, the elucidation of the genetic architecture of temperament is incomplete. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to analyze candidate genes related to bovine temperament, using bovine as the population, SNPs and genes as the exposure, and temperament test as the outcome, as principal search terms for population, exposure, and outcome (PEO) categories to define the scope of the search. The search results allowed the selection of 36 articles after removing duplicates and filtering by relevance. One hundred-two candidate genes associated with temperament traits were identified. The genes were further analyzed to construct an interaction network using the STRING database, resulting in 113 nodes and 346 interactions and the identification of 31 new candidate genes for temperament. Notably, the main genes identified were SST and members of the Kelch family. The candidate genes displayed interactions with pathways associated with different functions such as AMPA receptors, hormones, neuronal maintenance, protein signaling, neuronal regulation, serotonin synthesis, splicing, and ubiquitination activities. These new findings demonstrate the complexity of interconnected biological processes that regulate behavior and stress response in mammals. This insight now enables our targeted analysis of these newly identified temperament candidate genes in bovines.

Keywords: Kelch family genes; SST; behavior; cattle; splicing; temperament pathways; ubiquitination.

Figure 1

Workflow for selection of results returned using the PRISMA protocol 2020.

Figure 2

Participatory genes of the glutamine process pathway. (A) Interaction network among subunit γ calcium with AMPA subunit genes and new candidate gene (purple). (B) Glutamine-to-glutamate process describing the interaction of the AMPA cluster for reception of glutamate molecules with the new candidate gene (white).

Figure 3

Hormonal process for feeding behavior. (A) The hormones cluster shows the new candidate genes (purple) and genes previously related to bovine temperament (green). (B) Interaction pathway of new candidate genes (white), interacting as inhibitors of growth, feeding modulation, and enzymes for processing of hormones.

Figure 4

Clusters involved in neuronal processes. (A) Neuronal maintenance cluster, with new candidate gene (purple) and genes related to bovine temperament (green). (B) Principal activities of genes for neuronal maintenance, development, regulation, and differentiation. (C) Neuronal regulation cluster, with new candidate genes (purple) and genes related to bovine temperament (green).

Figure 5

Protein signaling pathways of new candidate genes. (A) Interaction network between new candidate genes (purple), with genes related to bovine temperament (green). (B) The participation of genes functioning through the protein signaling pathways involves different organelles, such as the nucleus, mitochondria, and rough endoplasmic reticulum.

Figure 6

Dopamine and serotonin production genes. (A) Neurotransmitters cluster. (B) Dopamine production genes (green), serotonin genes (brown), and not previously reported interacting genes (white). (C) Serotonin synthesis cluster with the new candidate gene AKR1B1 (purple).

Figure 7

Participation of new candidate genes in splicing pathways. (A) New candidate genes (purple) interact around the SNRPF gene. (B) Representation of the participation of splicing genes and their relationship to stress and metabolism.

Figure 8

Genes for the ubiquitination process. (A) The ubiquitination cluster shows the new candidate genes (purple). (B) Interactions of the new candidate genes with CUL3 gene are part of a different function for the CUL3 complex.