scholarly journals Genome-Wide Association Study Confirms Previous Findings of Major Loci Affecting Resistance to Piscine myocarditis virus in Atlantic Salmon (Salmo salar L.)

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 608 ◽  
Author(s):  
Borghild Hillestad ◽  
Ólafur H. Kristjánsson ◽  
Shokouh Makvandi-Nejad ◽  
Hooman K. Moghadam

Cardiomyopathy syndrome is a viral disease of Atlantic salmon, mostly affecting fish during the late stages of production, resulting in significant losses to the industry. It has been shown that resistance to this disease has a strong genetic component, with quantitative trait loci (QTL) on chromosomes 27 (Ssa27) and Ssa12 to explain most of the additive genetic variance. Here, by analysing animals from a different year-class and a different population, we further aimed to confirm and narrow down the locations of these QTL. The data support the existence of the two QTL and suggest that the causative mutation on Ssa27 is most likely within the 10–10.5 Mbp segment of this chromosome. This region contains a cluster of major histocompatibility complex class I (MHC I) genes with the most strongly associated marker mapped to one of these loci. On Ssa12, the data confirmed the previous finding that the location of the causative mutation is within the 61.3 to 61.7 Mbp region. This segment contains several immune-related genes, but of particular interest are genes related to MHC II. Together, these findings highlight the likely key role of MHC genes in Atlantic salmon following infection with Piscine myocarditis virus (PMCV) and their potential impact on influencing the trajectory of this disease.

2018 ◽  
Author(s):  
Borghild Hillestad ◽  
Hooman K. Moghadam

AbstractCardiomyopathy syndrome is a sever, viral disease of Atlantic salmon that mostly affects farmed animals during their late production stage at sea. Caused by piscine myocarditis virus (PMCV), over the past few years, the outbreaks due to this disease have resulted in significant losses to the aquaculture industry. However, there are currently no vaccine that has proven effective against this virus. In this study, using a challenge model, we investigate the genetic variation for robustness to PMCV, by screening large number of animals using a 55 K SNP array. In particular, we aimed to identify genetic markers that are tightly linked to higher disease resistance and can potentially be used in breeding programs. Using genomic information, we estimated heritability of 0.41 ±0.05, suggesting that robustness against this virus is largely controlled by genetic factors. Through association analysis, we identified a major QTL on chromosome 27, explaining approximately 57% of the total additive genetic variation. The region harbouring this putative QTL contains various immune related candidate genes, many of which have previously been shown to have a differential expression profile between the naïve and infected animals. We also identified a suggestive association on chromosome 12, where the QTL linked markers are located within two putatively immune related genes. These findings are important as they can be readily implemented into the breeding programs but also the results can further help in fine-mapping the causative mutation, in better understanding the biology of the disease and refine the mechanics of resistance against PMCV.


2019 ◽  
Vol 110 (6) ◽  
pp. 720-726 ◽  
Author(s):  
Borghild Hillestad ◽  
Hooman K Moghadam

Abstract Cardiomyopathy syndrome is a severe, viral disease of Atlantic salmon that mostly affects farmed animals during their late production stage at sea. Caused by piscine myocarditis virus (PMCV), over the past few years outbreaks due to this disease have resulted in significant losses to the aquaculture industry. However, there is currently no vaccine that has proven effective against this virus. In this study, using a challenge model, we investigated the genetic variation for resistance to PMCV, by screening a large number of animals using a 55 K SNP array. In particular, we aimed to identify genetic markers that are tightly linked to higher disease resistance and can potentially be used in breeding programs. Using genomic information, we estimated a heritability of 0.51 ± 0.06, suggesting that resistance against this virus, to a great extent, is controlled by genetic factors. Through association analysis, we identified a significant quantitative trait locus (QTL) on chromosome 27, explaining approximately 57% of the total additive genetic variation. The region harboring this QTL contains various immune-related candidate genes, many of which have previously been shown to have a different expression profile between the naïve and infected animals. We also identified a suggestive association on chromosome 12, with the QTL linked markers located in 2 putatively immune-related genes. These results are of particular interest, as they can readily be implemented into breeding programs, can further assist in fine-mapping the causative mutations, and help in better understanding the biology of the disease and the immunological mechanisms underlying resistance against PMCV.


2020 ◽  
Author(s):  
Devin Dersh ◽  
James D. Phelan ◽  
Megan E. Gumina ◽  
Boya Wang ◽  
Jesse H. Arbuckle ◽  
...  

SummaryTumors frequently subvert MHC class I (MHC-I) peptide presentation to evade CD8+ T cell immunosurveillance. To better define the regulatory networks controlling antigen presentation, we employed genome-wide screening in human diffuse large B cell lymphomas (DLBCLs). This approach revealed dozens of novel genes that positively and negatively modulate MHC-I cell surface levels. Identified genes cluster in multiple pathways including cytokine signaling, mRNA processing, endosomal trafficking, and protein metabolism. Many genes exhibit lymphoma subtype- or tumor-specific MHC-I regulation, and a majority of primary DLBCL tumors display genetic alterations in multiple regulators. We establish that the HSP90 co-chaperone SUGT1 is a major positive regulator of both MHC-I and MHC-II cell surface expression. Further, pharmacological inhibition of two negative regulators of antigen presentation, EZH2 and thymidylate synthase, enhances DLBCL MHC-I presentation. These and other genes represent potential targets for manipulating MHC-I immunosurveillance in cancers, infectious diseases, and autoimmunity.


2019 ◽  
Author(s):  
Wenwu Zhang ◽  
Jiguo Xu ◽  
Hongmei Li ◽  
Lianghui Zhou ◽  
Qinghua Nie ◽  
...  

Abstract Background As a major stressor, high temperatures negatively affect the poultry industry, through impairments to chicken immunity and production performance. The purpose of this study is to clarify how chicken immune systems responded to heat stress with and without immunization. In the present study, spleen and bursa of Fabricius of experimental chickens were subjected to RNA-seq. Key genes influencing immune response in heat-stressed chickens were identified and their functions validated. Results Immunized and heat-stressed chickens experienced a significant reduction in immune function. The expression of immune-related genes and heat stress-related genes in the spleen increased after immunization and decreased after heat stress, but in the bursa of Fabricius, few of these genes were differentially expressed after immunization and heat stress, indicating insensitivity to high temperature and the lack of vaccine processing. In the non-heat-stressed groups, spleen expression of DUSP1 and HSPA5 decreased significantly, suggesting their relationship to immunity. Upon DUSP1 or HSPA5 overexpression, the mRNA expression of MHC-I, MHC-II, CD80, CD86, CD1C, IL1B, IL6, and TLR4 was earlier than that under LPS stimulation only, indicating that DUSP1 or HSPA5 overexpression enhances HD11 recognition LPS. Inhibiting DUSP1 or HSPA5 expression, the mRNA expression levels of MHC-I, MHC-II, CD80, CD86, IL6 and TLR4 did not change significantly from LPS-stimulation-only levels but CD1C significantly decreased, suggesting that HD11 recognition of LPS is affected by DUSP1 or HSPA5 expression levels. Conclusions The inhibition of immune response due to lowly expressed DUSP1 and HSPA5 may be the cause of decreased immunity in chickens.


PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0119730 ◽  
Author(s):  
Alejandro P. Gutierrez ◽  
José M. Yáñez ◽  
Steve Fukui ◽  
Bruce Swift ◽  
William S. Davidson

2017 ◽  
Vol 8 (s1) ◽  
pp. s42-s44 ◽  
Author(s):  
M. E. Carvalho ◽  
F. S. Baldi ◽  
M. H. A. Santana ◽  
R. V. Ventura ◽  
G. A. Oliveira ◽  
...  

The aim of this study was to identify genomic regions that associated with beef tenderness in Nellore cattle. Phenotypes were obtained according to the standard USDA Quality Grade (1999). Data from 909 genotyped Nellore bulls were used in the Genome-Wide Association Study (GWAS) undertaken using a single-step approach including also a pedigree file composed of 6276 animals. The analyses were performed using the Blupf90 software, estimating the effect of genomic windows of 10 consecutive markers. The GWAS results identified 18 genomic regions located on 14 different chromosomes (1, 4, 6, 7, 8, 10, 18, 19, 20, 21, 22, 25, 26 and 29), which explained more than 1% of the total additive genetic variance; several candidate genes were located in these regions including SLC2A9, FRAS1, ANXA3, FAM219A, DNAI, AVEN, SHISA7, UBE2S, CDC42EP5, CNTN3, C16orf96, UBALD1, MGRN1 and SNORA1 With the single-step GWAS, it was possible to identify regions and genes related to meat tenderness in Nellore beef cattle.


Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 102
Author(s):  
Mingue Kang ◽  
Byeongyong Ahn ◽  
Seungyeon Youk ◽  
Yun-Mi Lee ◽  
Jong-Joo Kim ◽  
...  

Genetic analysis of the hair-length of Sapsaree dogs, a Korean native dog breed, showed a dominant mode of inheritance for long hair. Genome-Wide Association Study (GWAS) analysis and subsequent Mendelian segregation analysis revealed an association between OXR1, RSPO2, and PKHD1L1 on chromosome 13 (CFA13). We identified the previously reported 167 bp insertion in RSPO2 3’ untranslated region as a causative mutation for hair length variations. The analysis of 118 dog breeds and wolves revealed the selection signature on CFA13 in long-haired breeds. Haplotype analysis showed the association of only a few specific haplotypes to the breeds carrying the 167 bp insertion. The genetic diversity in the neighboring region linked to the insertion was higher in Sapsarees than in other Asian and European dog breeds carrying the same variation, suggesting an older history of its insertion in the Sapsaree genome than in that of the other breeds analyzed in this study. Our results show that the RSPO2 3’ UTR insertion is responsible for not only the furnishing phenotype but also determining the hair length of the entire body depending on the genetic background, suggesting an epistatic interaction between FGF5 and RSPO2 influencing the hair-length phenotype in dogs.


2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Leticia P. Sanglard ◽  
Yijian Huang ◽  
Kent A. Gray ◽  
Daniel C. L. Linhares ◽  
Jack C. M. Dekkers ◽  
...  

Abstract Background The possibility of using antibody response (S/P ratio) to PRRSV vaccination measured in crossbred commercial gilts as a genetic indicator for reproductive performance in vaccinated crossbred sows has motivated further studies of the genomic basis of this trait. In this study, we investigated the association of haplotypes and runs of homozygosity (ROH) and heterozygosity (ROHet) with S/P ratio and their impact on reproductive performance. Results There was no association (P-value ≥ 0.18) of S/P ratio with the percentage of ROH or ROHet, or with the percentage of heterozygosity across the whole genome or in the major histocompatibility complex (MHC) region. However, specific ROH and ROHet regions were significantly associated (P-value ≤ 0.01) with S/P ratio on chromosomes 1, 4, 5, 7, 10, 11, 13, and 17 but not (P-value ≥ 0.10) with reproductive performance. With the haplotype-based genome-wide association study (GWAS), additional genomic regions associated with S/P ratio were identified on chromosomes 4, 7, and 9. These regions harbor immune-related genes, such as SLA-DOB, TAP2, TAPBP, TMIGD3, and ADORA. Four haplotypes at the identified region on chromosome 7 were also associated with multiple reproductive traits. A haplotype significantly associated with S/P ratio that is located in the MHC region may be in stronger linkage disequilibrium (LD) with the quantitative trait loci (QTL) than the previously identified single nucleotide polymorphism (SNP) (H3GA0020505) given the larger estimate of genetic variance explained by the haplotype than by the SNP. Conclusions Specific ROH and ROHet regions were significantly associated with S/P ratio. The haplotype-based GWAS identified novel QTL for S/P ratio on chromosomes 4, 7, and 9 and confirmed the presence of at least one QTL in the MHC region. The chromosome 7 region was also associated with reproductive performance. These results narrow the search for causal genes in this region and suggest SLA-DOB and TAP2 as potential candidate genes associated with S/P ratio on chromosome 7. These results provide additional opportunities for marker-assisted selection and genomic selection for S/P ratio as genetic indicator for litter size in commercial pig populations.


Marine Drugs ◽  
2019 ◽  
Vol 17 (1) ◽  
pp. 66 ◽  
Author(s):  
Wei Zhang ◽  
Minseok Kwak ◽  
Hae-Bin Park ◽  
Takasi Okimura ◽  
Tatsuya Oda ◽  
...  

In our previous study, we showed that ascophyllan purified from Ascophyllum nodosum treatment promotes mouse dendritic cell (DC) activation in vivo, further induces an antigen-specific immune response and has anticancer effects in mice. However, the effect of ascophyllan has not been studied in human immune cells, specifically in terms of activation of human monocyte-derived DCs (MDDCs) and human peripheral blood DCs (PBDCs). We found that the treatment with ascophyllan induced morphological changes in MDDCs and upregulated co-stimulatory molecules and major histocompatibility complex class I (MHC I) and MHC II expression. In addition, pro-inflammatory cytokine levels in culture medium was also dramatically increased following ascophyllan treatment of MDDCs. Moreover, ascophyllan promoted phosphorylation of ERK, p38 and JNK signaling pathways, and inhibition of p38 almost completely suppressed the ascophyllan-induced activation of MDDCs. Finally, treatment with ascophyllan induced activation of BDCA1 and BDCA3 PBDCs. Thus, these data suggest that ascophyllan could be used as an immune stimulator in humans.


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