BoLA-DRB3 gene haplotypes show divergence in native Sudanese cattle from taurine and indicine breeds

AbstractAutochthonous Sudanese cattle breeds, namely Baggara for beef and Butana and Kenana for dairy, are characterized by their adaptive characteristics and high performance in hot and dry agro-ecosystems, are used largely by nomadic and semi-nomadic pastoralists. Here we analyzed the diversity and genetic structure of the BoLA-DRB3 gene, a genetic locus linked to the immune response, for the indigenous cattle of Sudan and in the context of the global cattle repository. Blood samples (n=225) were taken from three indigenous breeds (Baggara; n=113, Butana; n= 60 and Kenana; n=52) distributed across six regions of Sudan. Nucleotide sequences were genotyped using the sequence-based typing method. Sequence electropherograms were analyzed using the Assign SBT software. We describe 53 alleles, including seven new, novel alleles. In the Baggara breed the number of alleles was 46 (40 previously reported and six new ones), 33 in the Kenana breed (28 previously reported and five new ones), and 33 in the Butana breed (28 previously reported and five new ones). Venn analysis of Sudanese breeds with Southeast Asian, European and American cattle showed 115 alleles of which 14 were unique to Sudanese breeds. Three of the alleles exhibited gene frequency of > 0.5%, representing 26% of the 53 alleles detected in the native Sudanese cattle. Observed versus expected heterozygosity was higher than 0.93 in all three breeds analyzed and equilibrium status revealed by Hardy-Weinberg Equilibrium suggests pure genetic drift. Gene frequency distributions of Baggara cattle showed an even distribution (P = 0.016), consistent with the theoretical proportion expected under balancing selection pressure as opposed to positive or neutral selection. In contrast, Butana and Kenana cattle (P = 0.225 and P = 0.138, respectively) were more congruent with neutral selection, similar to the results obtained for most of the cattle breeds analyzed so far. Sudanese cattle breeds were located within a narrow cloud in an intermediate position between the Zebu and Taurine breeds and close to other Southeast Asian breeds, in accordance with the composite origin of these native breeds, which is also reinforced by the presence of African and Zebu unique BoLA-DRB3 alleles within these breeds. The results of the Principal Component Analysis were in agreement with the overall clustering pattern observed on the NJ and/or UPGMA trees. These results contribute to our understanding of the genetic diversity and distribution pattern of BoLA-DRB3 gene alleles in Sudanese cattle breeds and provide insight into their uniqueness in their ability to survive arrays of tropical diseases and reproduce well in Sudan’s harsh environment.Author summaryAfrican cattle survive and adapt to a variety of diseases via acquired immunity capable of presenting antigens through the function of the major histocompatibility complex (MHC) or bovine leukocyte antigen (BoLA) in cattle. The aim of this study was to investigate how the immune system is structured and to what extent three economically important breeds in Sudan differ from exotic cattle. Here, we use the sequence-based typing approach to analyze BoLA-DRB3’s genetic diversity linked to immunity against complex diseases that infect cattle. By examining 225 indigenous cattle belonging to three breeds in Sudan, we demonstrate that these cattle are unique from all known cattle by identifying seven new alleles; BoLA-DRB3*004:02Sp, BoLA-DRB3*011:02Sp, BoLA-DRB3*018:01Sp, BoLA-DRB3*021:01sp, BoLA-DRB3*024:18Sp, BoLA-DRB3*027:05sp, and BoLA-DRB3*032:01sp. When analyzing frequency of the protein pockets implicated in the antigen-binding function of the MHC complex by PCA we found that pockets 4 and 9 are the ones that best differentiate these native breeds from the rest. This may be attributed to high disease tolerance/susceptibility to tropical infections, such as those carried by ticks and intestinal parasites. Further studies are needed on these newly identified variants and their association with specific common disease(s). This finding is especially important for disease resistance/susceptibility association to help advise on candidate animals in selection schemes.

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Diversity of the BoLA-DRB3 Gene in Cattle Breeds From Tropical and Subtropical Regions of South America

10.21203/rs.3.rs-251864/v1 ◽

2021 ◽

Author(s):

Magali Nicole Valenzano ◽

María Eugenia Caffaro ◽

Veronica Viviana Lía ◽

Mario Poli ◽

Silvina Elizabeth Wilkowsky

Keyword(s):

Latin American ◽

Nucleotide Diversity ◽

Typing Method ◽

Exon 2 ◽

Peptide Recognition ◽

Cattle Breeds ◽

Leukocyte Antigens ◽

Neutrality Tests ◽

Gene Frequency Distribution

Abstract Background Bovine leukocyte antigens (BoLA) are widely used as markers of disease and immunological traits in cattle because of their primary function in the recognition of pathogens by the immune system. To date, however, the characterization of BoLA gene polymorphisms in Latin American Zebu and mixed zebuine breeds is scarce. By a sequence-based typing method, here we sequenced exon 2 of BoLA class II DRB3 gene of 264 animals from the five breeds (Creole, Brahman, Braford, Brangus and Nellore) most commonly used in northern Argentina. Results The taurine and zebuine breeds contained 61 previously reported alleles. Genetic diversity was high at allelic and molecular levels, particularly in the mixed breeds. Neutrality tests revealed that none of the breeds shows the even gene frequency distribution expected under a balanced selection scenario. The FST index shows significant differences across all populations (FST=0.052, P < 0.001), indicating a substantial differentiation between breeds. UPGMA trees and Metric multidimensional scaling (MDS) analysis show that, as expected, Creole is distantlyrelated to the other zebuinebreeds. Among them, Brahman, Braford and Brangus cluster closer together than with Nellore. These data are consistent with the historical and geographical origin of these breeds. A peptide binding region sequence analysis at the aminoacid level revealed that, despite the nucleotide diversity among the breeds, the key aminoacids involved in peptide recognition are greatly conserved. Conclusions This is the first report of BoLA-DRB3 diversity in pure and mixed zebuine cattle breeds from Argentina. Knowledge ofBoLA-DRB3 variability in breeds adapted to tropical and subtropical environments contributes not only to ongoing efforts to catalog bovine MHC allele frequencies by breed and location but also to the design of peptide-based vaccines.

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Characterization of bovine MHC DRB3 diversity in global cattle breeds, with a focus on cattle in Myanmar

10.21203/rs.3.rs-20143/v3 ◽

2020 ◽

Author(s):

Guillermo Giovambattista ◽

Kyaw Kyaw Moe ◽

Meripet Polat ◽

Liushiqi Borjigin ◽

Si Thu Hein ◽

...

Keyword(s):

Genetic Diversity ◽

Immune Response ◽

Latin American ◽

Coat Color ◽

Genetic Locus ◽

The Philippines ◽

Typing Method ◽

Cattle Breeds ◽

Holstein Friesian ◽

Native Populations

Abstract Background: Myanmar cattle populations predominantly consist of native cattle breeds (Pyer Sein and Shwe), characterized by their geographical location and coat color, and the Holstein-Friesian crossbreed, which is highly adapted to the harsh tropical climates of this region. Here, we analyzed the diversity and genetic structure of the BoLA-DRB3 gene, a genetic locus that has been linked to the immune response, in Myanmar cattle populations.Methods: Blood samples (n=294) were taken from two native breeds (Pyer Sein, n=163 and Shwe Ni, n=69) and a cattle crossbreed (Holstein-Friesian, n=62) distributed across six regions of Myanmar (Bago, n=38; Sagaing, n=77; Mandalay, n=46; Magway, n=46; Kayin, n=43; Yangon, n=44). In addition, a database that included 2,428 BoLA-DRB3 genotypes from European (Angus, Hereford, Holstein, Shorthorn, Overo Negro, Overo Colorado, and Jersey), Zebuine (Nellore, Brahman and Gir), Asian Native from Japan and Philippine and Latin-American Creole breeds was also included. Furthermore, the information from the IPD–MHC database was also used in the present analysis. DNA was genotyped using the sequence-based typing method. DNA electropherograms were analyzed using the Assign 400ATF software.Results: We detected 71 distinct alleles, including three new variants for the BoLA-DRB3 gene. Venn analysis showed that 11 of these alleles were only detected in Myanmar native breeds and 26 were only shared with Asian native and/or Zebu groups. The number of alleles ranged from 33 in Holstein-Friesians to 58 in Pyer Seins, and the observed versus unbiased expected heterozygosity were higher than 0.84 in all the three the populations analyzed. The FST analysis showed a low level of genetic differentiation between the two Myanmar native breeds (FST=0.003), and between these native breeds and the Holstein-Friesians (FST < 0.021). The average FST value for all the Myanmar Holstein-Friesian crossbred and Myanmar native populations was 0.0136 and 0.0121, respectively. Principal component analysis (PCA) and tree analysis showed that Myanmar native populations grouped in a narrow cluster that diverged clearly from the Holstein-Friesian populations. Furthermore, the BoLA-DRB3 allele frequencies suggested that while some Myanmar native populations from Bago, Mandalay and Yangon regions were more closely related to Zebu breeds (Gir and Brahman), populations from Kayin, Magway and Sagaing regions were more related to the Philippines native breeds. On the contrary, PCA showed that the Holstein-Friesian populations demonstrated a high degree of dispersion, which is likely the result of the different degrees of native admixture in these populations.Conclusion: This study is the first to report the genetic diversity of the BoLA-DRB3 gene in two native breeds and one exotic cattle crossbreed from Myanmar. The results obtained contribute to our understanding of the genetic diversity and distribution of BoLA-DRB3 gene alleles in Myanmar, and increases our knowledge of the worldwide variability of cattle BoLA-DRB3 genes, an important locus for immune response and protection against pathogens.

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Characterization of bovine MHC DRB3 diversity in global cattle breeds, with a focus on cattle in Myanmar

10.21203/rs.3.rs-20143/v2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Guillermo Giovambattista ◽

Kyaw Kyaw Moe ◽

Meripet Polat ◽

Liushiqi Borjigin ◽

Si Thu Hein ◽

...

Keyword(s):

Genetic Diversity ◽

Immune Response ◽

Latin American ◽

Coat Color ◽

Genetic Locus ◽

The Philippines ◽

Typing Method ◽

Cattle Breeds ◽

Holstein Friesian ◽

Native Populations

Abstract Background: Myanmar cattle populations predominantly consist of native cattle breeds (Pyer Sein and Shwe), characterized by their geographical location and coat color, and the Holstein-Friesian crossbreed, which is highly adapted to the harsh tropical climates of this region. Here, we analyzed the diversity and genetic structure of the BoLA-DRB3 gene, a genetic locus that has been linked to the immune response, in Myanmar cattle populations.Methods: Blood samples (n=294) were taken from two native breeds (Pyer Sein, n=163 and Shwe Ni, n=69) and a cattle crossbreed (Holstein-Friesian, n=62) distributed across six regions of Myanmar (Bago, n=38; Sagaing, n=77; Mandalay, n=46; Magway, n=46; Kayin, n=43; Yangon, n=44). In addition, a database that included 2,428 BoLA-DRB3 genotypes from European (Angus, Hereford, Holstein, Shorthorn, Overo Negro, Overo Colorado, and Jersey), Zebuine (Nellore, Brahman and Gir), Asian Native form Japan and Philippine and Latin-American Creole breeds was also included. Furthermore, the information from the IPD–MHC database was also used in the present analysis. DNA was genotyped using the sequence-based typing method. DNA electropherograms were analyzed using the Assign 400ATF software. Results: We detected 71 distinct alleles, including three new variants for the BoLA-DRB3 gene. Venn analysis showed that 11 of these alleles were only detected in Myanmar native breeds and 26 were only shared with Asian native and/or Zebu groups. The number of alleles ranged from 33 in Holstein-Friesians to 58 in Pyer Seins, and the observed versus unbiased expected heterozygosity were higher than 0.84 in all the three the populations analyzed. The FST analysis showed a low level of genetic differentiation between the two Myanmar native breeds (FST=0.003), and between these native breeds and the Holstein-Friesians (FST < 0.021). The average FST value for all the Myanmar Holstein-Friesian crossbred and Myanmar native populations was 0.0136 and 0.0121, respectively. Principal component analysis and tree analysis showed that Myanmar native populations grouped in a narrow cluster that diverged clearly from the Holstein-Friesian populations. Furthermore, the BoLA-DRB3 allele frequencies suggested that while some Myanmar native populations form Bago, Mandalay and Yangon regions were more closely related to Zebu breeds (Gir and Brahman), while populations from Kayin, Magway and Sagaing regions were more related to the Philippines native breeds. On the contrary, PCA showed that the Holstein-Friesian populations demonstrated a high degree of dispersion, which is likely the result of the different degrees of native admixture in these populations. Conclusion: This study is the first to report the genetic diversity of the BoLA-DRB3 gene in two native breeds and one exotic cattle crossbreed from Myanmar. The results obtained contribute to our understanding of the genetic diversity and distribution of BoLA-DRB3 gene alleles in Myanmar, and increases our knowledge of the worldwide variability of cattle BoLA-DRB3 genes, an important locus for immune response and protection against pathogens.

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Characterization of bovine MHC DRB3 diversity in global cattle breeds, with a focus on cattle in Myanmar

10.21203/rs.3.rs-20143/v1 ◽

2020 ◽

Author(s):

Guillermo Giovambattista ◽

Kyaw Kyaw Moe ◽

Meripet Polat ◽

Liushiqi Borjigin ◽

Si Thu Hein ◽

...

Keyword(s):

Coat Color ◽

Genetic Locus ◽

Geographical Location ◽

Principal Component ◽

The Philippines ◽

Typing Method ◽

Cattle Breeds ◽

Holstein Friesian ◽

Native Populations ◽

Tropical Climates

Abstract Background: Myanmar cattle populations predominantly consist of native cattle breeds, characterized by their geographical location and coat color, and the Holstein-Friesian crossbreed, which is highly adapted to the harsh tropical climates of this region. Here, we analyzed the diversity and genetic structure of the BoLA-DRB3 gene, a genetic locus that has been linked to the immune response, in Myanmar cattle populations.Methods: Blood samples (n=294) were taken from two native breeds (Pyer Sein, n=163 and Shwe Ni, n=69) and a cattle crossbreed (Holstein-Friesian, n=62) distributed across six regions of Myanmar (Bago, n=38; Sagaing, n=77; Mandalay, n=46; Magway, n=46; Kayin, n=43; Yangon, n=44). DNA was genotyped using the sequence-based typing method. DNA electropherograms were analyzed using the Assign 400ATF software. Results: We detected 71 distinct alleles, including three new variants for the BoLA-DRB3 gene. Venn analysis showed that 11 of these alleles were only detected in Myanmar native breeds and 26 were only shared with Asian native and/or Zebu groups. The number of alleles ranged from 33 in Holstein-Friesians to 58 in Pyer Seins, and the observed versus unbiased expected heterozygosity were higher than 0.84 in all the three the populations analyzed. The FST analysis showed a low level of genetic differentiation between the two Myanmar native breeds (FST=0.003), and between these native breeds and the Holstein-Friesians (FST < 0.021). The average FST value for all the Myanmar Holstein-Friesian crossbred and Myanmar native populations was 0.0136 and 0.0121, respectively. Principal component analysis (PCA) and tree analysis showed that Myanmar native populations grouped in a narrow cluster that diverged clearly from the Holstein-Friesian populations. Furthermore, the BoLA-DRB3 allele frequencies suggested that while some Myanmar native populations (Bago, Mandalay and Yangon) were more closely related to Zebu breeds (Gir and Brahman), others (Kayin, Magway and Sagaing) were more related to the native breeds found in the Philippines. On the contrary, the Holstein-Friesian populations demonstrated a high degree of dispersion, which is likely the result of the different degrees of native admixture in these populations. Conclusion: These results contribute to our understanding of the genetic diversity and distribution of BoLA-DRB3 gene alleles in Myanmar.

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Characterization of bovine MHC DRB3 diversity in global cattle breeds, with a focus on cattle in Myanmar

10.21203/rs.3.rs-20143/v4 ◽

2020 ◽

Author(s):

Guillermo Giovambattista ◽

Kyaw Kyaw Moe ◽

Meripet Polat ◽

Liushiqi Borjigin ◽

Si Thu Hein ◽

...

Keyword(s):

Genetic Diversity ◽

Immune Response ◽

Latin American ◽

Coat Color ◽

Genetic Locus ◽

The Philippines ◽

Typing Method ◽

Cattle Breeds ◽

Holstein Friesian ◽

Native Populations

Abstract Background: Myanmar cattle populations predominantly consist of native cattle breeds (Pyer Sein and Shwe), characterized by their geographical location and coat color, and the Holstein-Friesian crossbreed, which is highly adapted to the harsh tropical climates of this region. Here, we analyzed the diversity and genetic structure of the BoLA-DRB3 gene, a genetic locus that has been linked to the immune response, in Myanmar cattle populations.Methods: Blood samples (n=294) were taken from two native breeds (Pyer Sein, n=163 and Shwe Ni, n=69) and a cattle crossbreed (Holstein-Friesian, n=62) distributed across six regions of Myanmar (Bago, n=38; Sagaing, n=77; Mandalay, n=46; Magway, n=46; Kayin, n=43; Yangon, n=44). In addition, a database that included 2,428 BoLA-DRB3 genotypes from European (Angus, Hereford, Holstein, Shorthorn, Overo Negro, Overo Colorado, and Jersey), Zebuine (Nellore, Brahman and Gir), Asian Native from Japan and Philippine and Latin-American Creole breeds was also included. Furthermore, the information from the IPD–MHC database was also used in the present analysis. DNA was genotyped using the sequence-based typing method. DNA electropherograms were analyzed using the Assign 400ATF software. Results: We detected 71 distinct alleles, including three new variants for the BoLA-DRB3 gene. Venn analysis showed that 11 of these alleles were only detected in Myanmar native breeds and 26 were only shared with Asian native and/or Zebu groups. The number of alleles ranged from 33 in Holstein-Friesians to 58 in Pyer Seins, and the observed versus unbiased expected heterozygosity were higher than 0.84 in all the three the populations analyzed. The FST analysis showed a low level of genetic differentiation between the two Myanmar native breeds (FST=0.003), and between these native breeds and the Holstein-Friesians (FST < 0.021). The average FST value for all the Myanmar Holstein-Friesian crossbred and Myanmar native populations was 0.0136 and 0.0121, respectively. Principal component analysis (PCA) and tree analysis showed that Myanmar native populations grouped in a narrow cluster that diverged clearly from the Holstein-Friesian populations. Furthermore, the BoLA-DRB3 allele frequencies suggested that while some Myanmar native populations from Bago, Mandalay and Yangon regions were more closely related to Zebu breeds (Gir and Brahman), populations from Kayin, Magway and Sagaing regions were more related to the Philippines native breeds. On the contrary, PCA showed that the Holstein-Friesian populations demonstrated a high degree of dispersion, which is likely the result of the different degrees of native admixture in these populations. Conclusion: This study is the first to report the genetic diversity of the BoLA-DRB3 gene in two native breeds and one exotic cattle crossbreed from Myanmar. The results obtained contribute to our understanding of the genetic diversity and distribution of BoLA-DRB3 gene alleles in Myanmar, and increases our knowledge of the worldwide variability of cattle BoLA-DRB3 genes, an important locus for immune response and protection against pathogens.

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Plasmodium vivax Cysteine-Rich Protective Antigen Polymorphism at Exon-1 Shows Recombination and Signatures of Balancing Selection

Genes ◽

10.3390/genes12010029 ◽

2020 ◽

Vol 12 (1) ◽

pp. 29

Author(s):

Lilia González-Cerón ◽

José Cebrián-Carmona ◽

Concepción M. Mesa-Valle ◽

Federico García-Maroto ◽

Frida Santillán-Valenzuela ◽

...

Keyword(s):

Amino Acid ◽

B Cell ◽

Plasmodium Vivax ◽

Nucleotide Diversity ◽

Protective Antigen ◽

Balancing Selection ◽

Southern Mexico ◽

Exon 2 ◽

Exon 1 ◽

Tajima’S D

Plasmodium vivax Cysteine-Rich Protective Antigen (CyRPA) is a merozoite protein participating in the parasite invasion of human reticulocytes. During natural P. vivax infection, antibody responses against PvCyRPA have been detected. In children, low anti-CyRPA antibody titers correlated with clinical protection, which suggests this protein as a potential vaccine candidate. This work analyzed the genetic and amino acid diversity of pvcyrpa in Mexican and global parasites. Consensus coding sequences of pvcyrpa were obtained from seven isolates. Other sequences were extracted from a repository. Maximum likelihood phylogenetic trees, genetic diversity parameters, linkage disequilibrium (LD), and neutrality tests were analyzed, and the potential amino acid polymorphism participation in B-cell epitopes was investigated. In 22 sequences from Southern Mexico, two synonymous and 21 nonsynonymous mutations defined nine private haplotypes. These parasites had the highest LD-R2 index and the lowest nucleotide diversity compared to isolates from South America or Asia. The nucleotide diversity and Tajima’s D values varied across the coding gene. The exon-1 sequence had greater diversity and Rm values than those of exon-2. Exon-1 had significant positive values for Tajima’s D, β-α values, and for the Z (HA: dN > dS) and MK tests. These patterns were similar for parasites of different origin. The polymorphic amino acid residues at PvCyRPA resembled the conformational B-cell peptides reported in PfCyRPA. Diversity at pvcyrpa exon-1 is caused by mutation and recombination. This seems to be maintained by balancing selection, likely due to selective immune pressure, all of which merit further study.

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