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Title:   Author  item
                                            KIM, EUI-SOO - UWM MADISON, WIitem
                                            Lillehoj, Hyunitem
                                            LILLEHOJ, ERIK - UMSM BALTIMORE, MDitem
                                            SONG, KI-DUK - NIH BETHESDA, MD
  Submitted to: Poultry Science
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 9/12/2008
                                    Publication  Date: 10/20/2008
                                    Citation: Hong, Y.H., Kim, E., Lillehoj, H.S., Lillehoj, E.P., Song, K. 2008. Association of resistance to avian coccidiosis with single nucliotide polymorphisms in the zyxin gene. Poultry Science. 88:562-466.Interpretive Summary: Avian coccidiosis is caused by infection with protozoa and impairs the poultry industry by its detrimental influence on production efficiency such as survivability, nutrient absorption, growth rate, and egg production. Until now, disease control strategies against avian coccidiosis have mostly depended on prophylactic chemotherapy and vaccination, but both methods have serious drawbacks.  Genetic selection for disease resistance and immune responses can lead to a reduction of drug use and risk of vaccination in commercial poultry production. In this paper, ARS scientists investigated the nature of genetic variations associated with coccidiosis disease resistance phenotypes using commercial meat-type broiler chickens which are segregating for coccidiosis resistance. The rationale for this study originated from our prior reports that identified QTLs which are located on chicken chromosome 1 that control coccidiosis. Although these two markers supplied important information on the genetics of resistance to Eimeria infection, the region in which they are located is sufficiently large and may contain hundreds, if not thousands of candidate genes that are responsible for the observed phenotype.  As an initial approach to identify genetic elements that may influence the host response to coccidia infection, we selected 3 genes for further analysis, zyxin located at 80.67 Mb, CD4 at 80.36 Mb, and TNFRSF1A at 82.68 Mb.  Our results showed that a statistically significant association of resistance to avian coccidiosis occurred with SNPs in the zyxin gene.  Zyxin encodes a protein that functions as a component of focal adhesion complexes, regulates actin filament assembly, and promotes attachment of epithelial cells to the extracellular matrix.  Thus, it is tempting to speculate that one of the host responses to Eimeria infection involves up-regulation of the expression of genes such as zyxin that mediate focal adhesion, thereby promoting intestinal epithelial barrier formation against parasite invasion. Future studies will be needed to identify additional markers in other chicken families that may be associated with coccidiosis resistance phenotypes in other broiler chicken families and to develop markers for other candidate genes relevant to protective immunity.  Ultimately, these kind of research will facilitate the development of marker-assisted selection strategies to select chicken lines with enhanced resistance to avian coccidiosis.
                                Technical Abstract: Our previous genetic studies demonstrated that resistance to avian coccidiosis was linked with microsatellite markers LEI0071 and LEI0101 on chromosome 1.  In this study, the associations between parameters of resistance to coccidiosis and single nucleotide polymorphisms (SNPs) in 3 candidate genes located between LEI0071 and LEI0101 (zyxin, CD4, and TNFRSF1A) were determined.  SNPs were genotyped in 24 F1 generation and 290 F2 generation animals.  No SNPs were identified in the TNFRSF1A gene while 10 were located in the zyxin gene and 4 in the CD4 gene.  At various times following experimental infection of the F2 generation with Eimeria maxima, body weights, fecal oocyst shedding, and plasma levels of carotenoid, nitrite plus nitrate (NO2- + NO3-), and IFN-' were measured as parameters of resistance.  Single marker and haplotype-based tests were applied to determine the associations between the 14 SNPs and the parameters of coccidiosis resistance.  None of the CD4 SNPs were correlated with disease resistance.  However, by single marker association, several of the zyxin SNPs were significantly associated with elevated carotenoid or NO2- + NO3- concentrations.  These were the SNP at nucleotide 149 associated with increased carotenoid at day 3 post-infection (PI), nucleotide 187 with carotenoid at days 6 and 9 PI, and nucleotide 159 with carotenoid between days 3 and 9 PI.  In addition, the zyxin SNP at nucleotide 191 was significantly associated with increased levels of NO2- + NO3- at day 3 PI.  By haplotype association, the zyxin SNPs also were found to be highly associated with increased NO2- + NO3- at day 3 PI and increased IFN-' at day 6 PI.  These results suggest that zyxin is a candidate gene potentially associated with increased resistance to experimental avian coccidiosis.


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