title: Using a system of differential equations that models cattle growth to uncover the genetic basis of complex traits.
abstract: The interplay between dynamic models of biological systems and genomics is based on the assumption that genetic variation of the complex trait (i.e., outcome of model behavior) arises from component traits (i.e., model parameters) in lower hierarchical levels. In order to provide a proof of concept of this statement for a cattle growth model, we ask whether model parameters map genomic regions that harbor quantitative trait loci (QTLs) already described for the complex trait. We conducted a genome-wide association study (GWAS) with a Bayesian hierarchical LASSO method in two parameters of the Davis Growth Model, a system of three ordinary differential equations describing DNA accretion, protein synthesis and degradation, and fat synthesis. Phenotypic and genotypic data were available for 893 Nellore (Bos indicus) cattle. Computed values for parameter k1(DNA accretion rate) ranged from 0.005 ± 0.003 and for α (constant for energy for maintenance requirement) 0.134 ± 0.024. The expected biological interpretation of the parameters is confirmed by QTLs mapped for k1and α. QTLs within genomic regions mapped for k1are expected to be correlated with the DNA pool: body size and weight. Single nucleotide polymorphisms (SNPs) which were significant for α mapped QTLs that had already been associated with residual feed intake, feed conversion ratio, average daily gain (ADG), body weight, and also dry matter intake. SNPs identified for k1were able to additionally explain 2.2% of the phenotypic variability of the complex ADG, even when SNPs for k1did not match the genomic regions associated with ADG. Although improvements are needed, our findings suggest that genomic analysis on component traits may help to uncover the genetic basis of more complex traits, particularly when lower biological hierarchies are mechanistically described by mathematical simulation models.
authors.affiliation: Department of Veterinary Medicine, GMAB, Faculdade de Zootecnia e Engenharia de Alimentos, University of São Paulo, Av. Duque de Caxias Norte, 225, Pirassununga, SP, 13635-900, Brazil.
authors.forename: Mateus Castelani
authors.initials: MC
authors.lastname: Freua
authors.affiliation: Department of Veterinary Medicine, GMAB, Faculdade de Zootecnia e Engenharia de Alimentos, University of São Paulo, Av. Duque de Caxias Norte, 225, Pirassununga, SP, 13635-900, Brazil. miguel-has@hotmail.com.
authors.forename: Miguel Henrique de Almeida
authors.initials: MHA
authors.lastname: Santana
authors.affiliation: Department of Veterinary Medicine, GMAB, Faculdade de Zootecnia e Engenharia de Alimentos, University of São Paulo, Av. Duque de Caxias Norte, 225, Pirassununga, SP, 13635-900, Brazil.|Centre for Genetic Improvement for Livestock, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
authors.forename: Ricardo Vieira
authors.initials: RV
authors.lastname: Ventura
authors.affiliation: Department of Animal Science, Texas A&M University, 230 Kleberg Center, 2471 TAMU, College Station, TX, 77843, USA.
authors.forename: Luis Orlindo
authors.initials: LO
authors.lastname: Tedeschi
authors.affiliation: Department of Veterinary Medicine, GMAB, Faculdade de Zootecnia e Engenharia de Alimentos, University of São Paulo, Av. Duque de Caxias Norte, 225, Pirassununga, SP, 13635-900, Brazil.
authors.forename: José Bento Sterman
authors.initials: JBS
authors.lastname: Ferraz
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D049628:Body Size / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D002417:Cattle / Q000235:genetics* / Q000254:growth & development*; D056726:Genetic Association Studies; D005838:Genotype; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
keywords: Beef cattle; GWAS; Mechanistic modeling; Nellore; Performance