title: Genome-wide association study and biological pathway analysis of the Eimeria maxima response in broilers.
abstract: BACKGROUND
  Coccidiosis is the most common and costly disease in the poultry industry and is caused by protozoans of the Eimeria genus. The current control of coccidiosis, based on the use of anticoccidial drugs and vaccination, faces serious obstacles such as drug resistance and the high costs for the development of efficient vaccines, respectively. Therefore, the current control programs must be expanded with complementary approaches such as the use of genetics to improve the host response to Eimeria infections. Recently, we have performed a large-scale challenge study on Cobb500 broilers using E. maxima for which we investigated variability among animals in response to the challenge. As a follow-up to this challenge study, we performed a genome-wide association study (GWAS) to identify genomic regions underlying variability of the measured traits in the response to Eimeria maxima in broilers. Furthermore, we conducted a post-GWAS functional analysis to increase our biological understanding of the underlying response to Eimeria maxima challenge.
  
  
  RESULTS
  In total, we identified 22 single nucleotide polymorphisms (SNPs) with q value <0.1 distributed across five chromosomes. The highly significant SNPs were associated with body weight gain (three SNPs on GGA5, one SNP on GGA1 and one SNP on GGA3), plasma coloration measured as optical density at wavelengths in the range 465-510 nm (10 SNPs and all on GGA10) and the percentage of β2-globulin in blood plasma (15 SNPs on GGA1 and one SNP on GGA2). Biological pathways related to metabolic processes, cell proliferation, and primary innate immune processes were among the most frequent significantly enriched biological pathways. Furthermore, the network-based analysis produced two networks of high confidence, with one centered on large tumor suppressor kinase 1 (LATS1) and 2 (LATS2) and the second involving the myosin heavy chain 6 (MYH6).
  
  
  CONCLUSIONS
  We identified several strong candidate genes and genomic regions associated with traits measured in response to Eimeria maxima in broilers. Furthermore, the post-GWAS functional analysis indicates that biological pathways and networks involved in tissue proliferation and repair along with the primary innate immune response may play the most important role during the early stage of Eimeria maxima infection in broilers.
authors.affiliation: UMR1313 Animal Genetics and Integrative Biology Unit, AgroParisTech, 16 rue Claude Bernard, 75005, Paris, France. edin.hamzic@jouy.inra.fr.|UMR1313 Animal Genetics and Integrative Biology Unit, INRA, Domaine de Vilvert, 78350, Jouy-en-Josas, France. edin.hamzic@jouy.inra.fr.|Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, Blichers Allé 20, P.O. Box 50, 8830, Tjele, Denmark. edin.hamzic@jouy.inra.fr.
authors.forename: Edin
authors.initials: E
authors.lastname: Hamzić
authors.affiliation: Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, Blichers Allé 20, P.O. Box 50, 8830, Tjele, Denmark. bart.buitenhuis@mbg.au.dk.
authors.forename: Bart
authors.initials: B
authors.lastname: Buitenhuis
authors.affiliation: UMR1348 Physiology, Environment and Genetics for the Animal and Livestock Systems Unit, INRA, Domaine de la Prise, 35590, Saint Gilles, France. frederic.herault@rennes.inra.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Hérault
authors.affiliation: Cobb-Vantress Inc., Siloam Springs, AR, 72761, USA. rachel.hawken@cobb-vantress.com.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hawken
authors.affiliation: Cobb-Vantress Inc., Siloam Springs, AR, 72761, USA. mitch.abrahamsen@cobb-vantress.com.
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Abrahamsen
authors.affiliation: UMR1388 Genetics, Physiology and Breeding Systems, INRA, 24 chemin de Borde-Rouge, 31326, Castanet-Tolosan, France. bertrand.servin@toulouse.inra.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Servin
authors.affiliation: UMR1388 Genetics, Physiology and Breeding Systems, INRA, 24 chemin de Borde-Rouge, 31326, Castanet-Tolosan, France. jean-michel.elsen@toulouse.inra.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Elsen
authors.affiliation: UMR1313 Animal Genetics and Integrative Biology Unit, AgroParisTech, 16 rue Claude Bernard, 75005, Paris, France. marie-helene.pinard@jouy.inra.fr.|UMR1313 Animal Genetics and Integrative Biology Unit, INRA, Domaine de Vilvert, 78350, Jouy-en-Josas, France. marie-helene.pinard@jouy.inra.fr.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Pinard-van der Laan
authors.affiliation: UMR1313 Animal Genetics and Integrative Biology Unit, AgroParisTech, 16 rue Claude Bernard, 75005, Paris, France. bertrand.bedhom@jouy.inra.fr.|UMR1313 Animal Genetics and Integrative Biology Unit, INRA, Domaine de Vilvert, 78350, Jouy-en-Josas, France. bertrand.bedhom@jouy.inra.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bed'Hom
mesh_terms: D000465:Algorithms; D000818:Animals; D002645:Chickens / Q000235:genetics* / Q000378:metabolism* / Q000382:microbiology; D003048:Coccidiosis / Q000662:veterinary*; D004539:Eimeria; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D054884:Host-Pathogen Interactions; D008954:Models, Biological; D015233:Models, Statistical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011201:Poultry Diseases / Q000235:genetics* / Q000378:metabolism* / Q000382:microbiology; D019655:Quantitative Trait, Heritable; D015398:Signal Transduction