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Bovine Genome-wide Association Study for Genetic Elements to Resist the Infection of Foot-and-mouth Disease in the Field.

Lee BY, Lee KN, Lee T, Park JH, Kim SM, Lee HS, Chung DS, Shim HS, Lee HK, Kim H - Asian-australas. J. Anim. Sci. (2015)

Bottom Line: Among 624532 SNP after quality control, we found that 11 SNPs on 3 chromosomes (chr17, 22, and 15) were significantly associated with the trait at the p.adjust <0.05 after PERMORY test.Most significantly associated SNPs were located on chromosome 17, around the genes Myosin XVIIIB and Seizure related 6 homolog (mouse)-like, which were associated with lung cancer.Based on the known function of the genes nearby the significant SNPs, the FMD resistant animals might have ability to improve their innate immune response to FMDV infection.

View Article: PubMed Central - PubMed

Affiliation: Foot-and-Mouth Disease Division, Animal and Plant Quarantine Agency, Anyang 430-757, Korea .

ABSTRACT
Foot-and-mouth disease (FMD) is a highly contagious disease affecting cloven-hoofed animals and causes severe economic loss and devastating effect on international trade of animal or animal products. Since FMD outbreaks have recently occurred in some Asian countries, it is important to understand the relationship between diverse immunogenomic structures of host animals and the immunity to foot-and-mouth disease virus (FMDV). We performed genome wide association study based on high-density bovine single nucleotide polymorphism (SNP) chip for identifying FMD resistant loci in Holstein cattle. Among 624532 SNP after quality control, we found that 11 SNPs on 3 chromosomes (chr17, 22, and 15) were significantly associated with the trait at the p.adjust <0.05 after PERMORY test. Most significantly associated SNPs were located on chromosome 17, around the genes Myosin XVIIIB and Seizure related 6 homolog (mouse)-like, which were associated with lung cancer. Based on the known function of the genes nearby the significant SNPs, the FMD resistant animals might have ability to improve their innate immune response to FMDV infection.

No MeSH data available.


Related in: MedlinePlus

Manhattan plots showing the significant single nucleotide polymorphism (SNP) associated with the foot-and-mouth disease resistance. X-axis represents chromosome and Y-axis indicated −log10(p.adjust -value). Dots over the dotted line indicate significantly associated SNP.
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f1-ajas-28-2-166: Manhattan plots showing the significant single nucleotide polymorphism (SNP) associated with the foot-and-mouth disease resistance. X-axis represents chromosome and Y-axis indicated −log10(p.adjust -value). Dots over the dotted line indicate significantly associated SNP.

Mentions: We performed a GWAS of 96 female Holstein for FMDV resistance using the high density Bovine HD770K BeadChip. Out of 777,962 SNPs, a total of 624,532 were used for the association analysis after quality control. After PERMORY test, 11 SNP markers on 3 chromosomal locations showed the significant association with the FMDV resistance at p.adjust<0.05 (Figure 1). Three SNPs were located on chromosome 17, 7 on chromosome 22 and 1 on chromosome 15 (Table 2). Three SNPs on chr17 showed the most significant association and were located in the intergenic regions between Myosin XVIIIB (MYO18B) and seizure related 6 homolog (mouse)-like (SEZ6L). The MYO18B is known to be a tumor-suppressor gene and mutations in this gene are associated with lung cancer (Nishioka et al., 2002; Yokota et al., 2003; Tani et al., 2004; Yanaihara et al., 2004; Yokota and Kohno, 2004; Nakano et al., 2005). The Met430Ile polymorphic variant of SEZ6L has been previously linked with an increased risk of lung cancer in a human case-control population and the genetic and/or epigenetic alterations in SEZ6L might be involved in the development and/or progression in a subset of lung cancer (Nishioka et al., 2000; Gorlov et al., 2007). Among 7 significantly associated SNPs on chr22, 5 were spanning in the regions of CCDC36 (4 in introns and 1 in an exon) and 2 were in intergenic regions between CCDC36 and C22H3orf62. The SNP (rs110474439) in the exon of CCDC36 showed synonymous substitution. Due to the lack of knowledge on those genes, there are difficulties of understanding their function. However, ubiquitin specific peptidase 4 (USP4, proto-oncogene) that is 1 kb away from the C22H3orf62 plays an essential role in the negative regulation of the toll-like receptor/interleukin 1 receptor signaling-mediated innate immune response (Zhou et al., 2012). Although no SNPs in USP4 were significant at p.adjust<0.05 after PERMORY test, one (rs110159438) of them showed the association at p.adjust = 0.147 which was placed within top 20 markers. The SNP on Chr15 were located in an intron of DEAD box polypeptide 10 (DDX10), which is associated with leukemia (Nishiyama et al., 1999; Nakao et al., 2000; Morerio et al., 2006). Based on the known function of genes nearby the significant SNPs, we made inference that they might be involved in the functions related to innate immune responses. In contrast to adaptive immune system, induction of innate immune response by FMDV infection is still in a relatively early stage of understanding. One of major functions of the innate immune system is to act as a physical and chemical barrier to infectious agents (Janeway et al., 2001). The FMDV infects and replicates efficiently in epithelial cells (Summerfield et al., 2009). The epithelial surfaces of tissues that are in contact with the external environment, such as skin and the inner mucosa lining of the nose and lungs form a physical barrier which is very impermeable to most infectious agents and act as the first line of defense against invading organisms (Male, 2006). With respect to the respiratory airways and lungs, cilia movement helps to remove infectious agents and mucus traps infectious agents. The FMD resistant animals in this study seem to have ability to improve the innate immune responses to FMDV infection, even though further studies on the link between the genes and innate immune system are needed.


Bovine Genome-wide Association Study for Genetic Elements to Resist the Infection of Foot-and-mouth Disease in the Field.

Lee BY, Lee KN, Lee T, Park JH, Kim SM, Lee HS, Chung DS, Shim HS, Lee HK, Kim H - Asian-australas. J. Anim. Sci. (2015)

Manhattan plots showing the significant single nucleotide polymorphism (SNP) associated with the foot-and-mouth disease resistance. X-axis represents chromosome and Y-axis indicated −log10(p.adjust -value). Dots over the dotted line indicate significantly associated SNP.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4283160&req=5

f1-ajas-28-2-166: Manhattan plots showing the significant single nucleotide polymorphism (SNP) associated with the foot-and-mouth disease resistance. X-axis represents chromosome and Y-axis indicated −log10(p.adjust -value). Dots over the dotted line indicate significantly associated SNP.
Mentions: We performed a GWAS of 96 female Holstein for FMDV resistance using the high density Bovine HD770K BeadChip. Out of 777,962 SNPs, a total of 624,532 were used for the association analysis after quality control. After PERMORY test, 11 SNP markers on 3 chromosomal locations showed the significant association with the FMDV resistance at p.adjust<0.05 (Figure 1). Three SNPs were located on chromosome 17, 7 on chromosome 22 and 1 on chromosome 15 (Table 2). Three SNPs on chr17 showed the most significant association and were located in the intergenic regions between Myosin XVIIIB (MYO18B) and seizure related 6 homolog (mouse)-like (SEZ6L). The MYO18B is known to be a tumor-suppressor gene and mutations in this gene are associated with lung cancer (Nishioka et al., 2002; Yokota et al., 2003; Tani et al., 2004; Yanaihara et al., 2004; Yokota and Kohno, 2004; Nakano et al., 2005). The Met430Ile polymorphic variant of SEZ6L has been previously linked with an increased risk of lung cancer in a human case-control population and the genetic and/or epigenetic alterations in SEZ6L might be involved in the development and/or progression in a subset of lung cancer (Nishioka et al., 2000; Gorlov et al., 2007). Among 7 significantly associated SNPs on chr22, 5 were spanning in the regions of CCDC36 (4 in introns and 1 in an exon) and 2 were in intergenic regions between CCDC36 and C22H3orf62. The SNP (rs110474439) in the exon of CCDC36 showed synonymous substitution. Due to the lack of knowledge on those genes, there are difficulties of understanding their function. However, ubiquitin specific peptidase 4 (USP4, proto-oncogene) that is 1 kb away from the C22H3orf62 plays an essential role in the negative regulation of the toll-like receptor/interleukin 1 receptor signaling-mediated innate immune response (Zhou et al., 2012). Although no SNPs in USP4 were significant at p.adjust<0.05 after PERMORY test, one (rs110159438) of them showed the association at p.adjust = 0.147 which was placed within top 20 markers. The SNP on Chr15 were located in an intron of DEAD box polypeptide 10 (DDX10), which is associated with leukemia (Nishiyama et al., 1999; Nakao et al., 2000; Morerio et al., 2006). Based on the known function of genes nearby the significant SNPs, we made inference that they might be involved in the functions related to innate immune responses. In contrast to adaptive immune system, induction of innate immune response by FMDV infection is still in a relatively early stage of understanding. One of major functions of the innate immune system is to act as a physical and chemical barrier to infectious agents (Janeway et al., 2001). The FMDV infects and replicates efficiently in epithelial cells (Summerfield et al., 2009). The epithelial surfaces of tissues that are in contact with the external environment, such as skin and the inner mucosa lining of the nose and lungs form a physical barrier which is very impermeable to most infectious agents and act as the first line of defense against invading organisms (Male, 2006). With respect to the respiratory airways and lungs, cilia movement helps to remove infectious agents and mucus traps infectious agents. The FMD resistant animals in this study seem to have ability to improve the innate immune responses to FMDV infection, even though further studies on the link between the genes and innate immune system are needed.

Bottom Line: Among 624532 SNP after quality control, we found that 11 SNPs on 3 chromosomes (chr17, 22, and 15) were significantly associated with the trait at the p.adjust <0.05 after PERMORY test.Most significantly associated SNPs were located on chromosome 17, around the genes Myosin XVIIIB and Seizure related 6 homolog (mouse)-like, which were associated with lung cancer.Based on the known function of the genes nearby the significant SNPs, the FMD resistant animals might have ability to improve their innate immune response to FMDV infection.

View Article: PubMed Central - PubMed

Affiliation: Foot-and-Mouth Disease Division, Animal and Plant Quarantine Agency, Anyang 430-757, Korea .

ABSTRACT
Foot-and-mouth disease (FMD) is a highly contagious disease affecting cloven-hoofed animals and causes severe economic loss and devastating effect on international trade of animal or animal products. Since FMD outbreaks have recently occurred in some Asian countries, it is important to understand the relationship between diverse immunogenomic structures of host animals and the immunity to foot-and-mouth disease virus (FMDV). We performed genome wide association study based on high-density bovine single nucleotide polymorphism (SNP) chip for identifying FMD resistant loci in Holstein cattle. Among 624532 SNP after quality control, we found that 11 SNPs on 3 chromosomes (chr17, 22, and 15) were significantly associated with the trait at the p.adjust <0.05 after PERMORY test. Most significantly associated SNPs were located on chromosome 17, around the genes Myosin XVIIIB and Seizure related 6 homolog (mouse)-like, which were associated with lung cancer. Based on the known function of the genes nearby the significant SNPs, the FMD resistant animals might have ability to improve their innate immune response to FMDV infection.

No MeSH data available.


Related in: MedlinePlus