title: The Importance of Endophenotypes to Evaluate the Relationship between Genotype and External Phenotype.
abstract: With the exception of a few Mendelian traits, almost all phenotypes (traits) in livestock science are quantitative or complex traits regulated by the expression of many genes. For most of the complex traits, differential expression of genes, rather than genomic variation in the gene coding sequences, is associated with the genotype of a trait. The expression profiles of the animal's transcriptome, proteome and metabolome represent endophenotypes that influence/regulate the externally-observed phenotype. These expression profiles are generated by interactions between the animal's genome and its environment that range from the cellular, up to the husbandry environment. Thus, understanding complex traits requires knowledge about not only genomic variation, but also environmental effects that affect genome expression. Gene products act together in physiological pathways and interaction networks (of pathways). Due to the lack of annotation of the functional genome and ontologies of genes, our knowledge about the various biological systems that contribute to the development of external phenotypes is sparse. Furthermore, interaction with the animals' microbiome, especially in the gut, greatly influences the external phenotype. We conclude that a detailed understanding of complex traits requires not only understanding of variation in the genome, but also its expression at all functional levels.
authors.affiliation: Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, 6700AH Wageningen, The Netherlands. marinus.tepas@wur.nl.
authors.forename: Marinus F W
authors.initials: MF
authors.lastname: Te Pas
authors.affiliation: Animal Breeding and Genomics, Wageningen University, 6700AH Wageningen, The Netherlands. ole.madsen@wur.nl.
authors.forename: Ole
authors.initials: O
authors.lastname: Madsen
authors.affiliation: Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, 6700AH Wageningen, The Netherlands. mario.calus@wur.nl.
authors.forename: Mario P L
authors.initials: MP
authors.lastname: Calus
authors.affiliation: Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, 6700AH Wageningen, The Netherlands. mari.smits@wur.nl.
authors.forename: Mari A
authors.initials: MA
authors.lastname: Smits
mesh_terms: D000818:Animals; D058068:Endophenotypes; D057890:Epigenomics; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D023281:Genomics; D005838:Genotype; D058751:Livestock; D055432:Metabolomics; D010641:Phenotype; D040901:Proteomics; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D015398:Signal Transduction
keywords: bioinformatics; genomic variation and environment; integration; livestock science; metabolome; methylome; phenome; proteome; systems biology; transcriptome