Genome-Wide Association Study for Body Conformation Traits in Kazakh Fat-Tailed Coarse-Wool Sheep
Abstract
1. Introduction
2. Materials and Methods
2.1. Sample Collection and Data Record
2.2. DNA Extraction, Genotyping, and Quality Control
2.3. GWAS Analysis and Gene Annotation
2.4. Functional Enrichment Analysis of Candidate Genes
3. Results
3.1. Statistics of Phenotype
3.2. Genome-Wide Association Study
3.3. The KEGG Pathway and GO Enrichment Analyses
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ADAM12 | ADAM metallopeptidase domain 12 |
ADGRL3 | Adhesion G protein-coupled receptor L3 |
ANKRD44 | Ankyrin repeat domain 44 |
CALP | Calpastatin |
FGF12 | Fibrolast growth factor 12 |
FTO | FTO alpha-ketoglutarate dependent dioxygenase |
ELOVL2 | ELOVL fatty acid elongase 2 |
ERBB4 | Erb-B2 receptor tyrosine kinase 4 |
GWAS | Genome-wide association study |
HOXB13 | Homeobox B13 |
IGF-1 | Insulin-like growth factor 1 |
IGFBP6 | Insulin-like growth factor binding protein 6 |
MAS | Marker-assisted selection |
MACF1 | Microtubule Actin Crosslinking Factor 1 |
MSTN | Myostatin |
NCAPG | Non-SMC condensin I complex subunit G |
NEK1 | NIMA-related kinase 1 |
NRG1 | Neuregulin 1 |
PDGFD | Platelet-derived growth factor D |
RUNX1T1 | RUNX1 partner transcriptional co-repressor 1 |
SNP | Single-nucleotide polymorphisms |
VCAN | Versican |
References
- Tarlykov, P.; Atavliyeva, S.; Auganova, D.; Akhmetollayev, I.; Loshakova, T.; Varfolomeev, V.; Ramankulov, Y. Mitochondrial DNA analysis of ancient sheep from Kazakhstan: Evidence for early sheep introduction. Heliyon 2021, 7, e08011. [Google Scholar] [CrossRef]
- Parzhanov, Z.A.; Azhimetov, N.A.; Kistaubayev, Y.I.; Baibekov, Y.; Mustiyar, T.A. Inheritance of the fat tail parameters in the rams and ewes offsprings with different sizes of the fat tail. Pak. J. Zool. 2024, 57, 1123–1132. [Google Scholar] [CrossRef]
- Dossybayev, K.; Amandykova, M.; Orakbayeva, A.; Adylkanova, S.; Kozhakhmet, A.; Yergali, K.; Kulboldin, T.; Kulataev, B.; Torekhanov, A. Genome-wide association studies revealed several candidate genes of meat productivity in Saryarka fat-tailed coarse-wool sheep breed. Genes 2024, 15, 1549. [Google Scholar] [CrossRef] [PubMed]
- Zhumadillayev, N.; Dossybayev, K.; Khamzina, A.; Kapasuly, T.; Khamzina, Z.; Tlevlesov, N. SNP genotyping characterizes the genome composition of the new Baisary fat-tailed sheep breed. Animals 2022, 12, 1468. [Google Scholar] [CrossRef] [PubMed]
- Ataybekov, B.Y.; Prmanshaev, M.; Chortonbaev, T.D.; Bekturov, A.; Shergaziev, U.A. Meat productivity and interior features of fat-tailed coarse wool lambs in the south-east of Kazakhstan. BIO Web Conf. 2024, 83, 01006. [Google Scholar] [CrossRef]
- Xu, H.; Akhmet, N.; Luo, Y.; Guo, Z.; Pan, C.; Song, E.; Malmakov, N.; Akhatayeva, Z.; Lan, X. Are two beneficial mutations (p.Q249R and 90-bp Indel) within the ovine BMPRIB gene associated with growth traits? Front. Vet. Sci. 2024, 10, 1280548. [Google Scholar] [CrossRef]
- Liu, D.; Li, X.; Wang, L.; Pei, Q.; Zhao, J.; Sun, D.; Ren, Q.; Tian, D.; Han, B.; Jiang, H.; et al. Genome-wide association studies of body size traits in Tibetan sheep. BMC Genom. 2024, 25, 739. [Google Scholar] [CrossRef]
- Pan, Y.; Li, S.; Zhang, Q.; Li, J.; Song, C.; Kong, L.; Liu, Y.; Hou, S.; Li, S.; Liu, Q.; et al. Production performance analysis of sheep MSTN gene C2361T locus. J. Genet. Eng. Biotechnol. 2024, 22, 100372. [Google Scholar] [CrossRef]
- Aali, M.; Moradi-Shahrbabak, H.; Moradi-shahrbabak, M.; Sadeghi, M.; Yousefi, A.R. Association of the calpastatin genotypes, haplotypes, and SNPs with meat quality and fatty acid composition in two Iranian fat-and thin-tailed sheep breeds. Small Rumin. Res. 2017, 149, 40–51. [Google Scholar] [CrossRef]
- Kumar, S.; Dahiya, S.P.; Magotra, A.; Ratwan, P.; Bangar, Y. Influence of single nucleotide polymorphism in the IGF-1 gene on performance and conformation traits in Munjal sheep. Zygote 2023, 31, 70–77. [Google Scholar] [CrossRef]
- Ding, N.; Tian, D.; Li, X.; Zhang, Z.; Tian, F.; Liu, S.; Han, B.; Liu, D.; Zhao, K. Genetic Polymorphisms of IGF1 and IGF1R Genes and Their Effects on Growth Traits in Hulun Buir Sheep. Genes 2022, 13, 666. [Google Scholar] [CrossRef] [PubMed]
- Li, R.; Gong, M.; Zhang, X.; Wang, F.; Liu, Z.; Zhang, L.; Yang, Q.; Xu, Y.; Xu, M.; Zhang, H.; et al. A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes. Genome Res. 2023, 33, 463–477. [Google Scholar] [CrossRef] [PubMed]
- Ladeira, G.C.; Pilonetto, F.; Fernandes, A.C.; Bóscollo, P.P.; Dauria, B.D.; Titto, C.G.; Coutinho, L.L.; E Silva, F.F.; Pinto, L.F.B.; Mourão, G.B. CNV detection and their association with growth, efficiency and carcass traits in Santa Inês sheep. J. Anim. Breed. Genet. 2022, 139, 476–487. [Google Scholar] [CrossRef] [PubMed]
- Revelo, H.A.; López-Alvarez, D.; Palacios, Y.A.; Vergara, O.D.; Yánez, M.B.; Ariza, M.F.; Molina, S.L.C.; Sanchez, Y.O.; Alvarez, L.Á. Genome-wide association study reveals candidate genes for traits related to meat quality in Colombian Creole hair sheep. Trop. Anim. Health Prod. 2023, 55, 357. [Google Scholar] [CrossRef]
- Li, T.; Xing, F.; Zhang, N.; Chen, J.; Zhang, Y.; Yang, H.; Peng, S.; Ma, R.; Liu, Q.; Gan, S.; et al. Genome-wide association analysis of growth traits in Hu sheep. Genes 2024, 15, 1637. [Google Scholar] [CrossRef]
- Cao, Y.; Song, X.; Shan, H.; Jiang, J.; Xiong, P.; Wu, J.; Shi, F.; Jiang, Y. Genome-wide association study of body weights in Hu sheep and population verification of related single-nucleotide polymorphisms. Front. Genet. 2020, 11, 588. [Google Scholar] [CrossRef]
- Ma, L.; Zhao, W.; Ma, Q.; Wang, J.; Zhao, Z.; Zhang, J.; Gu, Y. Genome-wide association study of birth wool length, birth weight, and head color in Chinese Tan sheep through whole-genome re-sequencing. Animals 2024, 14, 3495. [Google Scholar] [CrossRef]
- Wang, S.; Liu, M.; Zhang, H.; He, S.; Li, W.; Liang, L. Genome-wide association study of body weight Traits in Texel and Kazakh crossbred sheep. Genes 2024, 15, 1521. [Google Scholar] [CrossRef]
- Purcell, S.; Neale, B.; Todd-Brown, K.; Thomas, L.; Ferreira, M.A.; Bender, D.; Maller, J.; Sklar, P.; de Bakker, P.I.; Daly, M.J.; et al. PLINK: A tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 2007, 81, 559–575. [Google Scholar] [CrossRef]
- Tuersuntuoheti, M.; Zhang, J.; Zhou, W.; Zhang, C.L.; Liu, C.; Chang, Q.; Liu, S. Exploring the growth trait molecular markers in two sheep breeds based on Genome-wide association analysis. PLoS ONE 2023, 18, e0283383. [Google Scholar] [CrossRef]
- Folahan, J.T.; Barabutis, N. NEK kinases in cell cycle regulation, DNA damage response, and cancer progression. Tissue Cell 2025, 94, 102811. [Google Scholar] [CrossRef]
- Noh, M.Y.; Oh, S.I.; Kim, Y.E.; Cha, S.J.; Sung, W.; Oh, K.W.; Park, Y.; Mun, J.Y.; Ki, C.S.; Nahm, M.; et al. Mutations in NEK1 cause ciliary dysfunction as a novel pathogenic mechanism in amyotrophic lateral sclerosis. Mol. Neurodegener. 2025, 20, 59. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Li, J.; Wang, H.; Zhang, R.; An, X.; Yuan, C.; Guo, T.; Yue, Y. Genomic selection for live weight in the 14th month in Alpine Merino sheep combining GWAS information. Animals 2023, 13, 3516. [Google Scholar] [CrossRef] [PubMed]
- Harten, I.A.; Kaber, G.; Agarwal, K.J.; Kang, I.; Ibarrientos, S.R.; Workman, G.; Chan, C.K.; Nivison, M.P.; Nagy, N.; Braun, K.R.; et al. The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation. Matrix Biol. 2020, 89, 27–42. [Google Scholar] [CrossRef]
- Islam, S.; Watanabe, H. Versican: A Dynamic Regulator of the Extracellular Matrix. J. Histochem. Cytochem. 2020, 68, 763–775. [Google Scholar] [CrossRef] [PubMed]
- Ma, X.F.; Liu, A.J.; Zheng, Z.; Hu, B.X.; Zhi, Y.X.; Liu, C.; Tian, S.J. Resolving and functional analysis of RNA editing sites in sheep ovaries and associations with litter size. Animal 2024, 18, 101342. [Google Scholar] [CrossRef]
- Dong, K.; Yang, M.; Han, J.; Ma, Q.; Han, J.; Song, Z.; Luosang, C.; Gorkhali, N.A.; Yang, B.; He, X.; et al. Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep. BMC Genom. 2020, 21, 800. [Google Scholar] [CrossRef]
- Xu, Y.X.; Wang, B.; Jing, J.N.; Ma, R.; Luo, Y.H.; Li, X.; Yan, Z.; Liu, Y.J.; Gao, L.; Ren, Y.L.; et al. Whole-body adipose tissue multi-omic analyses in sheep reveal molecular mechanisms underlying local adaptation to extreme environments. Commun. Biol. 2023, 6, 159. [Google Scholar] [CrossRef]
- Su, P.; Luo, Y.; Huang, Y.; Akhatayeva, Z.; Xin, D.; Guo, Z.; Pan, C.; Zhang, Q.; Xu, H.; Lan, X. Short variation of the sheep PDGFD gene is correlated with litter size. Gene 2022, 844, 146797. [Google Scholar] [CrossRef]
- Luo, Y.; Zhang, M.; Guo, Z.; Wijayanti, D.; Xu, H.; Jiang, F.; Lan, X. Insertion/Deletion (InDel) variants within the sheep fat-deposition-related PDGFD gene strongly affect morphological traits. Animals 2023, 13, 1485. [Google Scholar] [CrossRef]
- Onogi, Y.; Wada, T.; Kamiya, C.; Inata, K.; Matsuzawa, T.; Inaba, Y.; Kimura, K.; Inoue, H.; Yamamoto, S.; Ishii, Y.; et al. PDGFRβ regulates adipose tissue expansion and glucose metabolism via vascular remodeling in diet-induced obesity. Diabetes 2017, 66, 1008–1021. [Google Scholar] [CrossRef] [PubMed]
- Hu, N.; Zou, L.; Wang, C.; Song, G. RUNX1T1 function in cell fate. Stem Cell Res. Ther. 2022, 13, 369. [Google Scholar] [CrossRef] [PubMed]
- Deng, K.; Ren, C.; Liu, Z.; Gao, X.; Fan, Y.; Zhang, G.; Zhang, Y.; Ma, E.S.; Wang, F.; You, P. Characterization of RUNX1T1, an adipogenesis regulator in ovine preadipocyte differentiation. Int. J. Mol. Sci. 2018, 19, 1300. [Google Scholar] [CrossRef] [PubMed]
- Deng, K.; Liu, Z.; Su, Y.; Zhang, Z.; Fan, Y.; Zhang, Y.; Wang, F. RUNX1T1 modulates myogenic differentiation by regulating the calcium signaling pathway and the alternative splicing of ROCK2. FASEB J. 2023, 37, e23044. [Google Scholar] [CrossRef]
- Mei, L.; Nave, K.A. Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases. Neuron 2014, 83, 27–49. [Google Scholar] [CrossRef]
- Kataria, H.; Alizadeh, A.; Karimi-Abdolrezaee, S. Neuregulin-1/ErbB network: An emerging modulator of nervous system injury and repair. Prog. Neurobiol. 2019, 180, 101643. [Google Scholar] [CrossRef]
- Cordero, A.D.; Callihan, E.C.; Said, R.; Alowais, Y.; Paffhausen, E.S.; Bracht, J.R. Epigenetic regulation of neuregulin-1 tunes white adipose stem cell differentiation. Cells 2020, 9, 1148. [Google Scholar] [CrossRef]
- Huang, J.B.; Shen, Q.; Wang, Z.Q.; Ni, S.S.; Sun, F.; Hua, Y.; Huang, J.A. The influence of the NRG1/ERBB4 signaling pathway on pulmonary artery endothelial cells. Pulm. Circ. 2024, 14, e12439. [Google Scholar] [CrossRef]
- Chong, Y.; Xiong, H.; Gao, Z.; Lu, Y.; Hong, J.; Wu, J.; He, X.; Xi, D.; Tu, X.; Deng, W. Genomic and transcriptomic landscape to decipher the genetic basis of hyperpigmentation in Lanping black-boned sheep (Ovis aries). BMC Genom. 2024, 25, 845. [Google Scholar] [CrossRef]
- Coles, C.A.; Maksimovic, J.; Wadeson, J.; Fahri, F.T.; Webster, T.; Leyton, C.; McDonagh, M.B.; White, J.D. Knockdown of a disintegrin A metalloprotease 12 (ADAM12) during adipogenesis reduces cell numbers, delays differentiation, and increases lipid accumulation in 3T3-L1 cells. Mol. Biol. Cell 2018, 29, 1839–1855. [Google Scholar] [CrossRef]
- Kveiborg, M.; Albrechtsen, R.; Rudkjaer, L.; Wen, G.; Damgaard-Pedersen, K.; Wewer, U.M. ADAM12-S stimulates bone growth in transgenic mice by modulating chondrocyte proliferation and maturation. J. Bone Miner. Res. 2006, 21, 1288–1296. [Google Scholar] [CrossRef]
- Gualdrón Duarte, J.L.; Yuan, C.; Gori, A.S.; Moreira, G.C.M.; Takeda, H.; Coppieters, W.; Charlier, C.; Georges, M.; Druet, T. Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammals. Genet. Sel. Evol. 2023, 55, 83. [Google Scholar] [CrossRef]
- Esmaeili-Fard, S.M.; Gholizadeh, M.; Hafezian, S.H.; Abdollahi-Arpanahi, R. Genes and pathways affecting sheep productivity traits: Genetic parameters, genome-wide association mapping, and pathway enrichment analysis. Front. Genet. 2021, 12, 710613. [Google Scholar] [CrossRef]
- Tito, C.; Masciarelli, S.; Colotti, G.; Fazi, F. EGF receptor in organ development, tissue homeostasis and regeneration. J. Biomed. Sci. 2025, 32, 24. [Google Scholar] [CrossRef]
Traits | Mean ± SD | CV (%) | Min | Max |
---|---|---|---|---|
Live weight, (kg) | 63.1 ± 3.9 | 6.2 | 52 | 73 |
Withers height, (cm) | 74.2 ± 3.6 | 4.8 | 63 | 82 |
Rump height, (cm) | 75.7 ± 3.5 | 4.6 | 65 | 83 |
Chest width, (cm) | 25.7 ± 2.1 | 8.1 | 21 | 34 |
Chest depth, (cm) | 35.4 ± 1.7 | 4.9 | 29 | 40 |
Chest girth, (cm) | 101.5 ± 4.3 | 4.2 | 86 | 116 |
Oblique length, (cm) | 64.5 ± 3.4 | 5.3 | 55 | 75 |
Hip width, (cm) | 20.1 ± 2 | 9.8 | 15 | 25 |
Cannon bone circumference, (cm) | 9.2 ± 1 | 10.8 | 8 | 12 |
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Akhatayeva, Z.; Dossybayev, K.; Kozhakhmet, A.; Yermekova, M.; Kapassuly, T.; Yergali, K.; Kulboldin, T.; Torekhanov, A.; Kulataev, B.; Iskakov, K.; et al. Genome-Wide Association Study for Body Conformation Traits in Kazakh Fat-Tailed Coarse-Wool Sheep. Genes 2025, 16, 1023. https://doi.org/10.3390/genes16091023
Akhatayeva Z, Dossybayev K, Kozhakhmet A, Yermekova M, Kapassuly T, Yergali K, Kulboldin T, Torekhanov A, Kulataev B, Iskakov K, et al. Genome-Wide Association Study for Body Conformation Traits in Kazakh Fat-Tailed Coarse-Wool Sheep. Genes. 2025; 16(9):1023. https://doi.org/10.3390/genes16091023
Chicago/Turabian StyleAkhatayeva, Zhanerke, Kairat Dossybayev, Altynay Kozhakhmet, Marina Yermekova, Tilek Kapassuly, Kanagat Yergali, Temirlan Kulboldin, Aibyn Torekhanov, Beibit Kulataev, Kairat Iskakov, and et al. 2025. "Genome-Wide Association Study for Body Conformation Traits in Kazakh Fat-Tailed Coarse-Wool Sheep" Genes 16, no. 9: 1023. https://doi.org/10.3390/genes16091023
APA StyleAkhatayeva, Z., Dossybayev, K., Kozhakhmet, A., Yermekova, M., Kapassuly, T., Yergali, K., Kulboldin, T., Torekhanov, A., Kulataev, B., Iskakov, K., Kenzhebaev, T., & Lan, X. (2025). Genome-Wide Association Study for Body Conformation Traits in Kazakh Fat-Tailed Coarse-Wool Sheep. Genes, 16(9), 1023. https://doi.org/10.3390/genes16091023