Genome-wide association study and biological pathway analysis of the Eimeria maxima response in broilers

Abstract

BackgroundCoccidiosis 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.ResultsIn 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).ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-015-0170-0) contains supplementary material, which is available to authorized users.

SNP co-association and network analyses identify E2F3, KDM5A and BACH2 as key regulators of the bovine milk fatty acid profile

“…On the other hand, we also found some of our results to be inconsistent with previous studies. The most important differences were found on BTA14, where DGAT1 (located at ~1,8Mbp) is recognised as influencing the profile of several FA traits, including RA, 14:1, 16:1, 16:0, 18:1 c9 , 14:1 index, 16:1 index, 18:1 index 18:2 c9 , c12 , 18:3 c9 , c12 , c15 18 , 25 and milk fat 19 , 45 . In the present study, we also found a significant association with the milk fat but at a different position (~26.00 Mbp).…”

“…The integration of GWAS analysis with gene-set enrichment and network analyses turned out to be a valid means to extrapolate additional biological information and investigate the functional relationships among sets of genes, that individually explain only a relatively small part of phenotypic variation and therefore cannot be identified by GWAS due to the stringent significance threshold 25 . These approaches have been recently used to explore bovine reproductive 26 , 27 and productive traits 28 , 29 , and milk fat composition (including 10 FA traits) 19 and have provided new insights into the biological pathways, complex gene interactions and key regulators affecting the investigated traits.…”

Phenotypic and genetic variation in the response of chickens to Eimeria tenella induced coccidiosis

“…For example, some native chicken breeds, such as the Egyptian Fayoumi, appear to tolerate the pathological impacts of Eimeria infection [ 12 , 13 ], while distinct inbred lines of White Leghorn chickens support variable levels of parasite replication by different Eimeria species [ 14 ]. Biological pathways that may be indicative of resistance to Eimeria maxima infection have been noted in modern commercial broilers [ 15 , 16 ]. One genome-wide association study (GWAS) [ 16 ] alluded to the mechanisms of resistance to E. maxima including primary innate immune response, tissue repair, and proliferation.…”

“…Biological pathways that may be indicative of resistance to Eimeria maxima infection have been noted in modern commercial broilers [ 15 , 16 ]. One genome-wide association study (GWAS) [ 16 ] alluded to the mechanisms of resistance to E. maxima including primary innate immune response, tissue repair, and proliferation. Definitions of the immune categories used in this study are presented in Fig.…”

Genome-wide pleiotropy and shared biological pathways for resistance to bovine pathogens

“…To date, few studies have implemented biological pathway analysis in animal health [ 38 , 39 ]. This is the first study post-GWAS for resistance to most of all infection pathogens in dairy cattle.…”