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Identification and in silico characterization of structural and functional impacts of genetic variants in milk protein genes in the Zebu breeds Guzerat and Gyr

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Abstract

Whole genome sequencing of bovine breeds has allowed identification of genetic variants in milk protein genes. However, functional repercussion of such variants at a molecular level has seldom been investigated. Here, the results of a multistep Bioinformatic analysis for functional characterization of recently identified genetic variants in Brazilian Gyr and Guzerat breeds is described, including predicted effects on the following: (i) evolutionary conserved nucleotide positions/regions; (ii) protein function, stability, and interactions; (iii) splicing, branching, and miRNA binding sites; (iv) promoters and transcription factor binding sites; and (v) collocation with QTL. Seventy-one genetic variants were identified in the caseins (CSN1S1, CSN2, CSN1S2, and CSN3), LALBA, LGB, and LTF genes. Eleven potentially regulatory variants and two missense mutations were identified. LALBA Ile60Val was predicted to affect protein stability and flexibility, by reducing the number the disulfide bonds established. LTF Thr546Asn is predicted to generate steric clashes, which could mildly affect iron coordination. In addition, LALBA Ile60Val and LTF Thr546Asn affect exonic splicing enhancers and silencers. Consequently, both mutations have the potential of affecting immune response at individual level, not only in the mammary gland. Although laborious, this multistep procedure for classifying variants allowed the identification of potentially functional variants for milk protein genes.

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Acknowledgements

We thank the Centro Brasileiro de Melhoramento Genético do Guzerá (CBMG2), particularly Prof. Vânia Maldini Penna, Mrs. Ariane Menicucci, and Mr. Paulo Menicucci, for their enthusiasm with this project. We also thank the Associação Brasileira de Criadores do Gir (ABCG) and the Associação Brasileira de Criadores de Zebu (ABCZ) for technical support. We thank Mr. Peter Laspina for revising the English and for many valuable comments. We wish to thank the PDTIS-FIOCRUZ technology Platform RPT04B and Bioinformatics, BH.

Funding

CGRM was awarded a fellowship from the Coordenação de Pessoal de Nível Superior (CAPES); MRSC was awarded a fellowship from the Brazilian National Research Council (Conselho Nacional de Pesquisa, CNPq, grant numbers 312068/2015–8 and 312405/2018–9) and is supported by grants from the Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG) APQ-01093–15, APQ-02003–15, and APQ-01377–17; by the Instituto Nacional de Ciência e Tecnologia de Ciência Animal; and by the Pró-Reitoria de Pesquisa de Universidade Federal de Minas Gerais (PRPq/UFMG). MAM, MFM, and RSV received financial support from CNPq. ICR received a fellowship from FAPEMIG and, subsequently, from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). FSO and LRL received fellowships from a project funded by VALE. In addition, the present study was funded by the following agencies and projects: Empresa Brasileira de Pesquisa Agropecuária (Embrapa), CAPES, CNPq, FAPEMIG CBB-1181/0 and TCT 12.093/10 (MVBS), and 17003/2011 (MFM). GO was funded by RCUK (BB/P027849/1) Capacity building for bioinformatics in Latin America (CABANA) and CNPq (307479/2016–1).

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Authors and Affiliations

  1. Programa de Pós-Graduação Em GenéticaDepartamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31901-207, Brazil

    Carolina Guimarães Ramos Matosinho, Izinara Cruz Rosse, Pablo Augusto Souza Fonseca, Francislon Silva de Oliveira & Maria Raquel Santos Carvalho

  2. Departamento de Farmácia, Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, MG, 35400-000, Brazil

    Izinara Cruz Rosse

  3. Department of Animal Biosciences, Centre for Genetic Improvement of Livestock, University of Guelph, Guelph, ON, N1G2W1, Canada

    Pablo Augusto Souza Fonseca

  4. Grupo de Genômica E Biologia Computacional, Centro de Pesquisas René Rachou - Fiocruz Minas, Belo Horizonte, MG, 30190-00, Brazil

    Francislon Silva de Oliveira, Fausto Gonçalves dos Santos, Flávio Marcos Gomes Araújo, Anna Christina de Matos Salim & Guilherme Oliveira

  5. EPAMIG, Belo Horizonte, MG, 31170-495, Brazil

    Beatriz Cordenonsi Lopes & Rui da Silva Verneque

  6. Embrapa Gado de Leite, Juiz de Fora, MG, 36038-330, Brazil

    Wagner Antonio Arbex, Marco Antônio Machado, Maria Gabriela Campolina Diniz Peixoto, Rui da Silva Verneque, Marta Fonseca Martins & Marcos Vinicius Gualberto Barbosa da Silva

  7. Instituto Tecnológico Vale, Belém, PA, 66055-09, Brazil

    Guilherme Oliveira

  8. School of Computing and Information Systems, University of Melbourne, Parkville, VIC, 3052, Australia

    Douglas Eduardo Valente Pires

  9. Bio21 Institute, University of Melbourne, Parkville, VIC, 3052, Australia

    Douglas Eduardo Valente Pires

Authors
  1. Carolina Guimarães Ramos Matosinho
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  2. Izinara Cruz Rosse
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  3. Pablo Augusto Souza Fonseca
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  4. Francislon Silva de Oliveira
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  17. Maria Raquel Santos Carvalho
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Contributions

MRSC, GO, MVGBS, MAM, MGCDP, RSV, MFM: Conceptualization, Methodology, Data curation, Investigation, Resources, Project administration, Funding acquisition, Writing—review and editing. CGRM, ICR, PASF, FSO, FGS, FMGA, ACMS, BCL, WAA, DEVP: Methodology, Data curation, Investigation, Software, Visualization, Validation. CGRM: Writing—original draft. PASF: Writing—review and editing. All authors read and approved of the final manuscript.

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Correspondence to Pablo Augusto Souza Fonseca.

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Matosinho, C.G.R., Rosse, I.C., Fonseca, P.A.S. et al. Identification and in silico characterization of structural and functional impacts of genetic variants in milk protein genes in the Zebu breeds Guzerat and Gyr. Trop Anim Health Prod 53, 524 (2021). https://doi.org/10.1007/s11250-021-02970-2

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