Genome wide association study based on pathway analysis relate to wool traits in Zandi sheep breed

Mohammadi, Hossein; Moradi Shahrebabak, Hossein; Shamsollahi, Mohammad

doi:10.22059/jap.2023.357327.623738

Document Type : Research Paper

Authors

¹ Assistant Professor, Department of Animal Sciences, Faculty of Agriculture and Natural Resources, Arak University, Arak, Iran.

² Assistant Professor, Department of Animal Sciences, University College of Agriculture and Natural Resources, University of Tehran. Karaj.Iran

³ Assistant Professor, Department of Animal Sciences, Faculty of Agriculture, University of Ilam. Ilam, Iran.

10.22059/jap.2023.357327.623738

Abstract

Introduction: Identifying of genes with large effects on economically important traits, has been one of the important goal to sheep breeding. Over recent years, advances in DNA-based marker technology have made it possible to identify genomic regions or quantitative trait loci (QTLs) underlying complex traits, such as fleece traits, in sheep. The present study aimed to conduct a genome wide association studies (GWAS) based on gene-set enrichment analysis for identifying the loci associated with wool traits in native Zandi sheep using the 50K arrays.
Material and Methods: A total of 300 Iranian Zandi sheep used in this study came from the Zandi sheep breeding station. Wool sampling coincided with the maximum wool growth prior to the shearing of wool. In order to facilitate sampling, sheep were restrained in a lateral position and true wool from the left mid-side site was cut from a 5×5 cm² close to the skin using regular scissors. Each sample was separately packaged and labeled with ear tag number of the sheep. We measured and recorded four wool production traits: staple length (SL), mean fiber diameter (MFD), fiber diameter coefficient of variation (CVFD), and the proportion of fiber that are equal or more than 30 µm (PR), kemp percentage (KEMP%) and outer coat fiber (OCF) were measured. Genomic DNA extraction from sheep blood was performed by the applying a modified salting out protocol and genotyping of the Sheep SNPChip 50 K SNP Bead from Illumina Inc. The gene set analysis consists basically in three different steps: the assignment of SNPs to genes, the assignment of genes to functional categories, and finally the association analysis between each functional category and the phenotype of interest. Genome wide association study was performed with wool traits using GEMMA software. Using the biomaRt2 R package, the SNP were assigned to genes if they were within the genomic sequence of the gene or within a flanking region of 50 kb up- and downstream of the gene and bioinformatics analysis was implemented to identify the biological pathways performed in GO, KEEG, DAVID and PANTHER databases. The GO database designates biological descriptors to genes based on attributes of their encoded products and it is further partitioned into 3 components: biological process, molecular function, and cellular component. The KEGG pathway database contains metabolic and regulatory pathways, representing the actual knowledge on molecular interactions and reaction networks. Finally, a Fisher’s exact test was performed to test for overrepresentation of the significant genes for each gene-set. In the next step, a bioinformatics analysis was implemented to identify the biological pathways performed in GeneCards databases.
Result and Discussion: The result from genomic control showed weak population stratification with for woot traits among Zandi sheep population. We identified different sets of candidate genes related to wool traits including: CEP290, PRKCZ, TMTC3, RHPN2, TNFSF4, NLGN1, SPHKAP, PLCE1, FAT1 and PIK3R4 in Zandi sheep. Some of the found genes, are consistent with some of the previous studies related to reproductive traits. According to pathway analysis, 21 pathways from gene ontology and biological pathways were associated with the wool traits (P˂0.05). Some of the genes were found are consistent with some prior studies and to be involved biological pathways related to hair follicle development, keratinocytes differentiation, synthesizes an enzyme of threonine kinases, development of epidermal and Wnt signaling pathway.
Conclusion: In total, this study supported previous results from GWAS of wool traits, also revealed additional regions in the sheep genome associated with these economically important traits. These findings could potentially be useful for genetic selection in the breeding programs and can be used to understand the genetic mechanism controlling this trait.

Keywords

References

داشاب؛ غلامرضا، اسلمینژاد؛ علی‌اصغر، نصیری؛ محمدرضا، اسماعیل‌زاده کشکوئیه؛ علی و علی ساقی؛ داود (1391). تجزیه جایگاه های ژنی (QTL)، مؤثر بر صفات کمی و کیفی الیاف پشم در گوسفند بلوچی. مجله علوم دامی ایران، 43 (4)، 539-552.

Arzik, Y., Kizilaslan, M., Behrem, S., White, S.N., Piel, L.M.W., & Cinar, M.U. (2023). Genome-Wide Scan of Wool Production Traits in Akkaraman Sheep. Genes, 14, 713.

Bu, D., Luo, H., Huo, P., Wang, Z., Zhang, S., Liu, L., & Guo, J. (2021). KOBAS-i: intelligent prioritization and exploratory visualization of biological functions for gene enrichment analysis. Nucleic Acids Research, 49, 317-325.

Clancey, E., Kiser, J.N., Moraes, J.G.N., Dalton, J.C., Spencer, T.E., & Neibergs, H.L. (2019). Genome-wide association analysis and gene set enrichment analysis with SNP data identify genes associated with 305-day milk yield in Holstein dairy cows. Animal Genetics, (3), 254-258.

Dashab, G., Aslaminejad, A., Nasiri, M.R., Esmailizadeh, A., & Alisaghi, D. (2013). Analysis of Quantitative Trait Loci for Wool Traits in Baluchi Sheep. Iranian Journal of animal Science, 4, 539-552. (In Persian)

Esmaeili-Fard, S.M., Gholizadeh, M., Hafezian, S.H., & Abdollahi-Arpanahi, R. (2021). Genome-wide association study and pathway analysis identify NTRK2 as a novel candidate gene for litter size in sheep. PLoS One, 1, e0244408.

Fariello, M.I., Servin, B., Tosser-Klopp, G., Rupp, R., & Moreno, C. (2014). International Sheep Genomics Consortium; San Cristobal M, Boitard S. Selection signatures in worldwide sheep populations. PLoS One, 8, e103813.

Gay, D.L., Yang, C.C., Plikus, M.V., Ito, M., Rivera, C., Treffeisen, E., Doherty, L., Spata, M., Millar, S.E., & Cotsarelis, G. (2015). CD133 expression correlates with membrane betacatenin and E-cadherin loss from human hair follicle placodes during morphogenesis. Journal of Investigative Dermatology, 1, 45-55.

Lehman, J.M., Laag, E., Michaud, E.J., & Yoder, B.K. (2009). An Essential Role for Dermal Primary Cilia in Hair Follicle Morphogenesis. Journal of Investigative Dermatology, 129, 438-448.

Liu, C., Sello, C.T., Sun, Y., Zhou, Y., Lu, H., Sui, Y., Hu, J., Xu, C., Sun, Y., & Liu, J. (2018). De Novo Transcriptome Sequencing Analysis of Goose (Anser anser) Embryonic Skin and the Identification of Genes Related to Feather Follicle Morphogenesis at Three Stages of Development. International Journal of Molecular Sciences, 10, 3170.

Ma, G.W., You, X., & Yang, H. (2020). Polymorphisms and association of FAT1 gene with wool quality traits in Chinese Merino sheep. Czech Journal of Animal Science, 65, 31-39.

Marjanovic, J., & Calus, M.P.L. (2020). Factors affecting accuracy of estimated effective number of chromosome segments for numerically small breeds. Journal of Animal Breeding and Genetics, 138, 151-160.

McMullan, R., Lax, S., Robertson, V.H., Radford, D.J., Broad, S., Watt, F.M., Rowles, A., Croft, D.R., Olson, M.F., & Hotchin, N.A. (2003). Keratinocyte differentiation is regulated by the rho and ROCK signaling pathway. Current Biology, 24, 2185-2189.

Megdiche, S., Mastrangelo, S., Ben Hamouda, M., Lenstra, J.A., & Ciani, E. (2019). A combined multi-cohort approach reveals novel and known genome-wide selection signatures for wool traits in Merino and Merino-derived sheep breeds. Frontiers in Genetics, 10, 1025.

Mohammadi, H., Rafat, S.A., Moradi Shahrbabak, H., Shodja, J., & Moradi, M.H. (2020). Genome-wide association study and gene ontology for growth and wool characteristics in Zandi sheep. Journal of Livestock Science and Technologies, 8(2), 45-55.

Mohamadipoor Saadatabadi, L., Mohammadabadi, M., Amiri Ghanatsaman, Z., Babenko, O., Stavetska, R., Kalashnik, O., Kucher, D., Kochuk-Yashchenko, O., & Asadollahpour Nanaei, H. (2021). Signature selection analysis reveals candidate genes associated with production traits in iranian sheep breeds. BMC Veterinary Research, 17(1), 369.

Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D., Maller, J., Sklar, P., de Bakker, P.I., Daly, M., & Sham, P.C. (2007). PLINK: a tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics, 3, 559-575.

Ren, X., Yang, G.L., Peng, W.F., Zhao, Y.X., Zhang, M., Chen, Z.H., Wu, F.A., Kantanen, J., Shen, M., & Li, M.H. (2016). A genome-wide association study identifies a genomic region for the polycerate phenotype in sheep (Ovis aries). Scientific Reports, 6, 21111.

Roldan, D.L., Dodero, A.M., Bidinost, F., Taddeo, H.R., Allain, D., Zhang, M., & Li, S. (2010). Merino sheep: a further look at quantitative trait loci for wool production. Animal, 4, 1330-1340.

Takahashi, T., Kamimura, A., Shirai, A., & Yokoo, Y. (2000). Several Selective Protein Kinase C Inhibitors Including Procyanidins Promote Hair Growth. Characterization of Reconstructed Skin Models, 13, 133-142.

Wang, L., Jia, P., & Wolfinger, R.D. (2011). Gene set analysis of genome-wide association studies: Methodological issues and perspectives. Genomics, 98, 1-8.

Wang, Z., Zhang, H., Yang, H., Wang, S., Rong, E., Pei, W., Li, H., & Wang, N. (2014). Genome-wide association study for wool production traits in a Chinese Merino sheep population. PLoS One, 9, e107101.

Young, M.D., Wakefield, M.J., Smyth, G.K., & Oshlack, A. (2010). Method gene ontology analysis for RNA-seq: Accounting for selection bias. Genome Biology, 11, 14-23.

Zhao, H., Zhu, S., Guo, T., Han, M., Chen, B., Qiao, G., Wu, Y., Yuan, C., Liu, J., Lu, Z., Sun, W., Wang, T., Li, F., Zhang, Y., Hou, F., Yue, Y., & Yang, B. (2021). Whole-genome re-sequencing association study on yearling wool traits in Chinese fine-wool sheep. Journal of Animal Science, 9, skab210.

Zhou, X., & Stephens, M. (2012). Genome-wide efficient mixed-model analysis for association studies. Nature Genetics, 44, 821.

Animal Production

Genome wide association study based on pathway analysis relate to wool traits in Zandi sheep breed

References

References

Volume 25, Issue 3
October 2023
Pages 241-254

Genome wide association study based on pathway analysis relate to wool traits in Zandi sheep breed

References

References

Volume 25, Issue 3October 2023Pages 241-254

Volume 25, Issue 3
October 2023
Pages 241-254