Genome-Wide Association Study in Mexican Holstein Cattle Reveals Novel Quantitative Trait Loci Regions and Confirms Mapped Loci for Resistance to Bovine Tuberculosis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Tissue Samples
2.2. Bacteriological Analysis
2.3. Experimental Design, DNA Extraction, Pooling and Genotyping
2.4. Statistical Analysis of Pool
2.5. Quantitative Trait Loci Region Definition
2.6. Functional Annotation of the QTLR
3. Results
QTLRs Associated with Resistance/Susceptibility to bTB
4. Discussion
4.1. QTLR_1%_PFP
4.2. QTLR_5%_PFP
4.2.1. BTA 1
4.2.2. BTA 3
4.2.3. BTA 5
4.2.4. BTA 13
4.3. QTLR_10%_PFP
BTA 2
- Cathepsins, including Cathepsin S (CTSS) are proteolytic enzymes that function mainly in lysosomes, where they contribute to pathogen killing by their involvement in antigen presentation pathways. Pires et al. [59] demonstrated the role of this class of proteins in the control of M. tuberculosis by manipulating the cathepsin expression by pathogenic mycobacteria to favor its intracellular survival.
- The protein encoded by the CD80 gene (CD80 molecule), the B-lymphocyte activation antigen B7-1 is a membrane receptor that affects the immunological reactivity of T-lymphocytes when its expression decreases. In addition, CD80 has a role in enhancing the anti-tuberculosis immunity [60].
- The FCGR1A gene (Fc fragment of IgG receptor Ia) expression, together with that of the BLR1 gene has been considered as potential marker for monitoring the extent of TB disease and to predict treatment outcome in children affected by M. tuberculosis [61].
- Booty et al. [62] reported that the cytokine IL-21, produced predominantly by activated CD4+ T cells and CD8+ T cells, is an essential signaling marker for host resistance to M. tuberculosis infection via the IL-21 receptor (IL-21R).
- Gomes-Pereira et al. [63] reported an increased susceptibility to M. avium in Hemochromatosis Protein HFE-Deficient Mice. HEF (homeostatic iron regulator) is a fundamental protein involved in the regulation of cellular iron uptake and iron homeostasis. Studies indicate that monocytes with mutated HFE have decreased intracellular iron levels [64]. Also, Wang at el. [65] demonstrated that hemochromatosis impacts the regulation of macrophage cytokine translation and, consequently the inflammatory response.
- The ANO9 gene, also known as TMEM16J (anoctamin 9), together with the SIGIRR and the PKP3 genes constitute a polymorphic complex associated with susceptibility to tuberculosis [66]. The SIGIRR gene, also known as Toll IL-1 receptor 8, is a regulatory protein acting to inhibit ILRs and TLRs signaling [67]. The PKP3, the third part of this complex gene, maps 6.2 Kb from the end of the QTLR_152.
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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CASES | CONTROLS | ||||
---|---|---|---|---|---|
Biological | Technical | Biological | Technical | ||
Bio_rep a | Pool_Rep b | Array_Rep c | Bio_rep a | Pool_Rep b | Array_Rep c |
CA_1 | CA1_A | CA_1A_1 | CT_1 | CT1_A | CT_1A_1 |
CA_1A_2 | CT_1A_2 | ||||
CA_1A_3 | CT_1A_3 | ||||
CA1_B | CA_1B_1 | CT1_B | CT_1B_1 | ||
CA_1B_2 | CT_1B_2 | ||||
CA_1B_3 | CT_1B_3 | ||||
CA_2 | CA2_A | CA_2A_1 | CT_2 | CT2_A | CT_2A_1 |
CA_2A_2 | CT_2A_2 | ||||
CA_2A_3 | CT_2A_3 | ||||
CA2_B | CA_2B_1 | CT2_B | CT_2B_1 | ||
CA_2B_2 | CT_2B_2 | ||||
CA_2B_3 | CT_2B_3 | ||||
CT_3 | CT3_A | CT_3A_1 | |||
CT_3A_3 | |||||
CT_3A_3 | |||||
CT3_B | CT_3B_1 | ||||
CT_3B_3 | |||||
CT_3B_3 |
Term | Count | p-Value | Genes |
---|---|---|---|
Biological process | |||
GO:0006334: nucleosome assembly | 6 | 9.42 × 105 | HIST1H2BB, HIST1H1C, HIST1H1A, H2B, HIST1H3G, HIST1H3I |
GO:0006335: DNA replication-dependent nucleosome assembly | 3 | 6.12 × 103 | H4, HIST1H3G, HIST1H3I |
GO:0051290: protein heterotetramerization | 3 | 6.81 × 103 | H4, HIST1H3G, HIST1H3I |
GO:0098792: xenophagy | 5 | 2.27 × 103 | TMEM39A, SNRPB2, CPA3, HIST1H3G, HIST1H3I |
GO:0002230: positive regulation of defense response to virus by host | 5 | 3.68 × 103 | TMEM39A, SNRPB2, CPA3, HIST1H3G, HIST1H3I |
GO:0046627: negative regulation of insulin receptor signaling pathway | 3 | 9.09 × 103 | PRKCD, KANK1, PRKCB |
GO:0042742: defense response to bacterium | 4 | 1.63 × 102 | STAB1, FCGR1A, PRKCD, TMF1 |
Cellular Components | |||
GO:0000786: nucleosome | 7 | 1.60 × 105 | H4, HIST1H1C, HIST1H1A, H2B, HIST1H2AK, HIST1H3G, HIST1H3I |
GO:0000788: nuclear nucleosome | 5 | 2.47 × 104 | HIST1H2BB, H2B, HIST1H3G, HIST1H3I |
GO:0000784: nuclear chromosome, telomeric region | 4 | 2.3 × 102 | H4, TNKS, HIST1H3G, HIST1H3I |
GO:0030176: integral component of endoplasmic reticulum membrane | 4 | 1.50 × 102 | PIGG, SARAF, MBOAT4, SLC27A2 |
GO:0005615: extracellular space | 13 | 3.32 × 102 | A2M, H2B, HFE, FSTL1, CTSS, OVOS2, ESF1, VEGFC, GPI, CTSK, CPA3, CPB1, SMARCA4 |
GO:0005788: endoplasmic reticulum lumen | 3 | 4.77 × 102 | EOGT, SLC27A2, POGLUT1 |
Molecular Functions | |||
GO:0046982: protein heterodimerization activity | 5 | 7.15 × 103 | AGTR1, HIST1H2BB, H4, H2B, FOXP1 |
GO:0042393: histone binding | 3 | 3.67 × 102 | H4, PRKCB, SMARCA4 |
KEGG Pathways | |||
bta05322: Systemic lupus erythematosus | 9 | 7.64 × 108 | HIST1H2BB, H4, CD80, FCGR1A, HIST2H2BF, H2B, HIST1H2AK, HIST1H3G, HIST1H3I |
bta05034: Alcoholism | 8 | 4.32 × 106 | HIST1H2BB, HRAS, H4, HIST2H2BF, H2B, HIST1H2AK, HIST1H3G, HIST1H3I |
bta05203: Viral carcinogenesis | 5 | 1.92 × 103 | HIST1H2BB, HRAS, H4, HIST2H2BF, H2B |
bta00514: Other types of O-glycan biosynthesis | 3 | 2.18 × 102 | ST6GAL2, EOGT, POGLUT1 |
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González-Ruiz, S.; Strillacci, M.G.; Durán-Aguilar, M.; Cantó-Alarcón, G.J.; Herrera-Rodríguez, S.E.; Bagnato, A.; Guzmán, L.F.; Milián-Suazo, F.; Román-Ponce, S.I. Genome-Wide Association Study in Mexican Holstein Cattle Reveals Novel Quantitative Trait Loci Regions and Confirms Mapped Loci for Resistance to Bovine Tuberculosis. Animals 2019, 9, 636. https://doi.org/10.3390/ani9090636
González-Ruiz S, Strillacci MG, Durán-Aguilar M, Cantó-Alarcón GJ, Herrera-Rodríguez SE, Bagnato A, Guzmán LF, Milián-Suazo F, Román-Ponce SI. Genome-Wide Association Study in Mexican Holstein Cattle Reveals Novel Quantitative Trait Loci Regions and Confirms Mapped Loci for Resistance to Bovine Tuberculosis. Animals. 2019; 9(9):636. https://doi.org/10.3390/ani9090636
Chicago/Turabian StyleGonzález-Ruiz, Sara, Maria G. Strillacci, Marina Durán-Aguilar, Germinal J. Cantó-Alarcón, Sara E. Herrera-Rodríguez, Alessandro Bagnato, Luis F. Guzmán, Feliciano Milián-Suazo, and Sergio I. Román-Ponce. 2019. "Genome-Wide Association Study in Mexican Holstein Cattle Reveals Novel Quantitative Trait Loci Regions and Confirms Mapped Loci for Resistance to Bovine Tuberculosis" Animals 9, no. 9: 636. https://doi.org/10.3390/ani9090636