Detection of a mutation in the intron 7 of B4GALNT2 gene and its association with Litter size in Shal breed

Authors
Mohamad Mahdi Bagheri AmirAbadi 1
Hamid Ghasemzadeh nava 2
Aidin Rahim Tayefeh 3
Farid Heydari 3
1 DVSc Student, Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran, Tehran- Iran.
2 Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran, Tehran- Iran.
3 Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIIGEB), Tehran- Iran.
10.22034/ijvcs.2024.14815.1091
Abstract
The gene B4GALNT2, with 12 Exons, is located on chromosome 11. This gene is associated with the production of the B4GALNT2 protein, which functions as a transferase in the final step of synthesizing the Sda antigen. In the Lacaune breed, a mutation known as FecLL (g.36938224T>A) in intron 7 of this gene has been found to have a positive effect on fertility and multiple births. Considering the effect of multiple births in the small ruminant industry, an investigation was conducted to explore the presence of the FecLl mutation and other potential mutation near its location in part of the intron 7 of B4GALNT2 gene. Two groups of multiple birth and single birth, each containing 20 shal ewes were selected for blood collection, DNA extraction and sanger sequencing, based on their reproductive histories of last 5 year of lambing records and the current breeding season. The sequence analysis revealed the absence of the FecLL mutation in the samples. However, three other mutations were identified: g.37129493 T>C, g.37129812 C>A, and g.37130289 T>A. No significant differences were observed between the two study groups regarding these mutations (P > 0.05). Based on these findings, it appears that the FecLL mutation may not be present in the Shal breed. However, due to the occurrence of the mutations in the intron and their potential low impact on the final protein, further investigation of the gene network and a larger sample size is recommended to explore other phenotypic associations and detect additional mutation.
Keywords
Twinning
Singleton
Shal Breed
Gene
B4GALNT2
Sequencing
Single Nucleotide Mutation
Subjects
  1. Akbarinejad, V; Kazempoor, R; Shojaei, Mr and Rezaee M; Oji R; Atlas of Iranian Sheep Breeds; Noorbakhs; Tehran, 2014; pp : 86-87. 
  2. Ben Jemaa, S; Ruesche, J; Sarry, J; Woloszyn, F; Lassoued, N; Fabre, S; The high prolificacy of D’man sheep is associated with the segregation of the FecLL mutation in the B4GALNT2 gene. Reprod. Domest. Anim; 2019;54(3):531-7. 
  3. Bodin, L; SanCristobal, M; Lecerf, F; Mulsant, P; Bibé, B; Lajous, D; Belloc, J-P; Eychenne; Amigues, Y and Elsen, J-M; Segregation of a major gene influencing ovulation in progeny of Lacaune meat sheep. Genet. Sel. Evol; 2002;34(4):447-64. 
  4. Drouilhet, L; Mansanet, C; Sarry, J; Tabet, K; Bardou P, Woloszyn F; The highly prolific phenotype of Lacaune sheep is associated with an ectopic expression of the B4GALNT2 gene within the ovary. PLoS Genet; 2013;9(9):e1003809. 
  5. Drouilhet, L; Taragnat, C; Fontaine, J; Duittoz, A; Mulsant, P; Bodin, L and Fabre, S; Endocrine characterization of the reproductive axis in highly prolific Lacaune sheep homozygous for the FecLL mutation. Biol. Reprod; 2010;82(5):815-24. 
  6. Duca, M; Malagolini, N; Dall’Olio, F; The story of the Sda antigen and of its cognate enzyme B4GALNT2: What is new? Glycoconj J; 2023;40(1):123-33. 
  7. Easton, RL; Patankar, MS; Lattanzio, FA; Leaven, TH; Morris, HR; Clark, GF; et al; Structural analysis of murine zona pellucida glycans: evidence for the expression of core 2-type Oglycans and the Sda antigen. J. Biol. Chem; 2000;275(11):7731-42. 
  8. GAO, Yi-Jie WJ; CHAO, Lu-Meng; CANG, Ming; YU, Hai-Quan; WANG, Jian-Guo; BAO, Si-Qin; LIU, YongBin; ZHANG, Wen-Guang; MA, Qing and TONG, Bin; Association Between
    Polymorphisms in B4GALNT2 Gene and Litter Size in Mongolia Sheep and Ujimqin Sheep (Ovis aries). J. Agric. Biotechnol; 2022;30(8):1510 - 23. 
  9. Groux-Degroote, S; Wavelet, C; Krzewinski-Recchi, M-A; Portier, L; Mortuaire, M; Mihalache, A; Maro, T; Delannoy, P; Malagolini, N; Chiricolo, M; Dall'olio, F and Harduin-Lepers,  ;
    B4GALNT2 gene expression controls the biosynthesis of Sda and sialyl Lewis X antigens in healthy and cancer human gastrointestinal tract. Int. J. Biochem. Cell. Biol; 2014;53:442-9.
  10. X; Wang, X; Liang, B; Di, R; Liu, Q; Hu, W; He, X; Zhang, J;Zhang, X and Chu, M; Molecular cloning of the B4GALNT2 gene and its single nucleotide polymorphisms association with litter size in small tail han sheep. J. Anim; 2018;8(10):160.
  11. Ji, X; Cao, Z; Hao, Q; He, M; Cang, M; Yu, H; Ma, Q; Li, X; Bao, S; Wang, J and Tong, B; Effects of New Mutations in BMPRIB, GDF9, BMP15, LEPR, and B4GALNT2  Genes on Litter Size in Sheep. Vet. Sci; 2023;10(4):258.
  12. Johnsen, JM; Levy, GG; Westrick, RJ; Tucker, PK; Ginsburg, D; The endothelial-specific regulatory mutation, Mvwf1, is a common mouse founder allele. Mammalian Genome; 
    2008;19:32-40. 
  13. Johnsen, JM; Teschke, M; Pavlidis, P;  McGee, BM; Tautz, D; Ginsburg, D and Baines, JF; Selection on cisregulatory variation at B4galnt2 and its influence on von Willebrand factor in house mice. Molecular biology and  evolution; 2009;26(3):567-78.
  14. Klisch, K; Contreras, D; Sun, X; Brehm, R; Bergmann, M and Alberio,  R; The Sda/GM2-glycan is a carbohydrate marker of porcine primordial germ cells and of a subpopulation of spermatogonia in cattle, pigs, horses and llama. Reprod; 2011;142(5):667-674. 
  15. Klisch, K; Jeanrond, E; Pang, P-C; Pich, A; Schuler, G; Dantzer, V; Kowalewski, M-P and Dell, A; A tetraantennary glycan with bisecting Nacetylglucosamine and the Sda antigen
    is the predominant N-glycan on bovine pregnancy-associated glycoproteins. J. Glycobiol; 2008;18(1):42-52. 
  16. Li, P-T; Liao, C-J, Wu, W-G; Yu, L-C and Chu, ST; Progesterone-regulated B4galnt2 expression is a requirement for embryo implantation in mice. Int. J. Fertil. Steril;  011;95(7):2404-9. e3.
  17. Linnenbrink, M; Johnsen, JM; Montero, I; Brzezinski, CR; Harr, B; Baines, JF; Long-term balancin selection at the blood group-related gene B4galnt2 in the genus Mus (Rodentia; Muridae). Mol. Biol. Evol; 2011;28(11):2999-3003. 
  18. Malagolini, N; Dall'Olio, F; Di Stefano, G; Minni, F; Marrano, D; Serafini-Cessi, F; Expression of UDPGalNAc: NeuAcα2, 3Galβ-R β1, 4 (GalNAc to Gal)  acetylgalactosaminyltransferase involved in the synthesis of Sda antigen in human large intestine and colorectal carcinomas. Cancer Res. J; 1989;49(23):6466-70. 
  19. Malagolini, N; Santini, D; Chiricolo, M and Dall'Olio, F; Biosynthesis and expression of the Sda and sialyl Lewis x antigens in normal and cancer colon. Glycobiol; 2007;17(7):688-97. 
  20. Pucci, M; Gomes, Ferreira, I; Orlandani, M; Malagolini, N; Ferracin, M and Dall’Olio, F; High expression of the Sda synthase B4GALNT2 associates with good prognosis and
    attenuates stemness in colon cancer. Cell. J; 2020;9(4):948.
  21. Pucci, M; Malagolini, N and Dall’Olio, F; Glycosyltransferase b4galnt2 as a predictor of good prognosis in colon cancer: Lessons from databases. Int. J. Mol. Sci; 2021;22(9):4331.
  22. Salehi, A; Rostami, F; Bakhtiari, Zadeh MR; Study of B4GALNT2 (FecL) gene mutation by using High Resolution Melting (HRM) technique in Zandi sheep. Mod. Genet; 2022;17(1):87-90. 
  23. Talebi, R; Ahmadi, A; Afraz, F; Sarry, J; Woloszyn, F; Fabre, S; Detection of single nucleotide polymorphisms at major prolificacy genes in the Mehraban sheep and association with
    litter size. Ann. Anim. Sci; 2018;18(3):685-98. 
Iranian Journal of Veterinary Clinical Sciences
Volume 18, Issue 1 - Serial Number 30
Spring & Summer 2024
August 2024
Pages 109-117