Polymorphism of three ovine BMP15, INHBA and INHA candidate genes for litter size in four Iranian Indigenous sheep using PCR-sequencing

Document Type : Original Research Article (Regular Paper)

Authors

Department of Animal Science, Faculty of Agricultural Science, University of Yasouj, Yasouj, Iran

Abstract

The inhibin α (INHA), inhibin βA (INHBA) and bone morphogenetic protein 15 (BMP-15) were investigated as candidate genes for reproductive traits in four Iranian sheep breeds (Bahmaei, Lak Ghashghaei, Lori-Bakhtiari and Karakul). Based on the ovine sequences of BMP-15, INHA and INHBA genes, three pairs of primers were designed to identify single nucleotide polymorphisms (SNPs) in exon 2 of BMP-15, INHA and INHBA in multiparous ewes by DNA sequencing. Two SNPs were detected in exon 2 of the ovine BMP15 gene at positions 367 and 430, which lead to amino acid substitutions at position 231 and 252 in the BMP15 protein sequence, respectively. Substitution of Leucine to Proline at position 252 is predicted to affect the protein function. A synonymous mutation was found in the amplified fragment of exon 2 at position 752 in ovine INHBA gene. In addition, the c752C>T mutation was only found in heterozygous condition in only one Lori-Bakhtiari ewe, while other breeds were in wild type genotype for c752C>T mutation. The INHA gene was shown to be highly polymorphic. A total of 7 SNPs including 6 nucleotide substitutions and one insertion were found in the amplified fragment of the INHA locus. The insertion mutation was found in two animals of Bahmaei and Karakul breeds. Interestingly, homozygous condition for the mutant alleles in all identified SNPs in BMP15, INHA and INHBA loci was absent in these breeds. Generally, these breeds showed different genetic structures with regard to the identified SNPs in BMP15, INHBA and INHA genes. However, further research with larger sample size and phenotype data on reproductive performance is required to investigate the definitive effect of the identified mutations in this study.

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References

References
Abdoli, R., Mirhoseini, S.Z., Hossein-Zadeh, N.G., Zamani, P., 2018. Screening for causative mutations of major prolificacy genes in Iranian fat-tailed sheep. International Journal of Fertility & Sterility 12, 51-55.
Bao, Y., Yao, X., Li, X., Ei-Samahy, M.A., Yang, H., Liang, Y., Liu, Z.,  Wang, F., 2021. INHBA transfection regulates proliferation, apoptosis and hormone synthesis in sheep granulosa cells. Theriogenology 175, 111-122.
Bernard, D.J., Chapman, S.C., Woodruff, T.K., 2001. Mechanisms of inhibin signal transduction. Recent Progress in Hormone Research 56, 417-450.
Bodin, L., Di Pasquale, E., Fabre, S., Bontoux, M., Monget, P., Persani, L., Mulsant, P., 2007. A novel mutation in the bone morphogenetic protein 15 gene causing defective protein secretion is associated with both increased ovulation rate and sterility in Lacaune sheep. Endocrinology 148, 393-400.
Chen, M.-J., Chou, C.H., Chen, S.U., Yang, W.S., Yang, Y.S., Ho, H.N., 2015. The effect of androgens on ovarian follicle maturation: Dihydrotestosterone suppress FSH-stimulated granulosa cell proliferation by upregulating PPARγ-dependent PTEN expression. Scientific Reports 5, 1-13.
Chu, M., Xiao, C., Fu, Y., Fang, L., Ye, S., 2007. PCR-SSCP polymorphism of inhibin βA gene in some sheep breeds. Asian-Australasian Journal of Animal Sciences 20, 1023-1029.
Chu, M., Zhuang, H., Zhang, Y., Jin, M., Li, X., Di, R., Cao, G., Feng, T., Fang, L., 2011. Polymorphism of inhibin βB gene and its relationship with litter size in sheep. Animal Science Journal 82, 57-61.
Chu, Y. L., Xu, Y R., Yang, W.X., Sun, Y., 2018. The role of FSH and TGF-β superfamily in follicle atresia. Aging (Albany NY) 10, 305-321.
Davis, G., Montgomery, G., Allison, A., Kelly, R., Bray, A., 1982. Segregation of a major gene influencing fecundity in progeny of Booroola sheep. New Zealand Journal of Agricultural Research 25, 525-529.
Demars, J., Fabre, S., Sarry, J., Rossetti, R., Gilbert, H., Persani, L., Tosser-Klopp, G., Mulsant, P., Nowak, Z., Drobik, W., 2013. Genome-wide association studies identify two novel BMP15 mutations responsible for an atypical hyperprolificacy phenotype in sheep. PLoS Genetics 9, e1003482.
Fang, L., Chang, H.M., Cheng, J.C., Leung, P.C., Sun, Y.P., 2014. TGF-β1 induces COX-2 expression and PGE2 production in human granulosa cells through Smad signaling pathways. The Journal of Clinical Endocrinology & Metabolism 99, 1217-1226.
Fortune, J., Yang, M., Muruvi, W., 2010. The earliest stages of follicular development: follicle formation and activation. Society of Reproduction and Fertility Supplement 67, 203-216.
Galloway, S.M., McNatty, K.P., Cambridge, L.M., Laitinen, M.P., Juengel, J.L., Jokiranta, T.S., McLaren, R.J., Luiro, K., Dodds, K.G., Montgomery, G.W., 2000. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nature Genetics 25, 279-283.
Ghiasi, H., Nasiry, M.R., Heravi Mousavi, A.R., Mousavizadeh, A.A., Javadmanesh, A., 2006. Genetic polymorphism of the melatonin receptor 1A locus in Iranian Shall and Karakul sheep. Iranian Journal of Biotechnology 4, 201-203.
Hanrahan, J.P., Gregan, S.M., Mulsant, P., Mullen, M., Davis, G.H., Powell, R., Galloway, S.M., 2004. Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biology of Reproduction 70, 900-909.
Ishigame, H., Medan, M.S., Watanabe, G., Shi, Z., Kishi, H., Arai, K.Y., Taya, K., 2004. A new alternative method for superovulation using passive immunization against inhibin in adult rats. Biology of Reproduction 71, 236-243.
Juengel, J.L., Hudson, N.L., Heath, D.A., Smith, P., Reader, K.L., Lawrence, S.B., O’Connell, A.R., Laitinen, M.P., Cranfield, M., Groome, N.P., 2002. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep. Biology of Reproduction 67, 1777-1789.
Kaczor U. (2017) Genes involved litter size in Olkuska sheep. In: Narasimha Reddy Parine, Parine, N.R. (Ed.), Genetic Polymorphisms. King Saud University, Saudi Arabia, pp. 251-273.
Kondi-Pafiti, A., Grigoriadis, C., Samiotaki, D., Filippidou-Giannopoulou, A., Kleanthis, C., Hassiakos, D., 2013. Immunohistochemical study of inhibin A and B expression in placentas from normal and pathological gestations. Clinical and Experimental Obstetrics & Gynecology 40, 109-112.
Li, H.W.R., Anderson, R.A., Yeung, W.S.B., Ho, P.C., Ng, E.H.Y., 2011. Evaluation of serum antimullerian hormone and inhibin B concentrations in the differential diagnosis of secondary oligoamenorrhea. Fertility and Sterility 96, 774-779.
Martinez‐Royo, A., Jurado, J., Smulders, J., Marti, J., Alabart, J., Roche, A., Fantova, E., Bodin, L., Mulsant, P., Serrano, M., 2008. A deletion in the bone morphogenetic protein 15 gene causes sterility and increased prolificacy in Rasa Aragonesa sheep. Animal Genetics 39, 294-297.
Mason, A.J., Hayflick, J.S., Ling, N., Esch, F., Ueno, N., Ying, S.Y., Guillemin, R., Niall, H., Seeburg, P.H., 1985. Complementary DNA sequences of ovarian follicular fluid inhibin show precursor structure and homology with transforming growth factor-β. Nature 318, 659-663.
McNatty, K., Heath, D., Hudson, N., Ball, K., Condell, L., 1992. Concentrations of immunoreactive inhibin in ovarian and peripheral venous plasma and follicular fluid of Booroola ewes that are homozygous carriers or non-carriers of the FecB gene. Reproduction 95, 489-502.
McNatty, K.P., Smith, P., Moore, L., Reader, K., Lun, S., Hanrahan, J., Groome, N.P., Laitinen, M., Ritvos, O., Juengel, J.L., 2005. Oocyte-expressed genes affecting ovulation rate. Molecular and Cellular Endocrinology 234, 57-66.
Medan, M., Akagi, S., Kaneko, H., Watanabe, G., Tsonis, C., Taya, K., 2004. Effects of re-immunization of heifers against inhibin on hormonal profiles and ovulation rate. Reproduction 128, 475-482.
Mingxing, C., Rong, C., Guohong, C., Li, F., Sucheng, Y., 2005. Study on bone morphogenetic protein 15 as a candidate gene for prolificacy of Small Tail Han sheep and Hu Sheep. Journal of Anhui Agricultural University 32, 278-282.
Monteagudo, L.V., Ponz, R., Tejedor, M.T., Laviña, A., Sierra, I., 2009. A 17 bp deletion in the Bone Morphogenetic Protein 15 (BMP15) gene is associated to increased prolificacy in the Rasa Aragonesa sheep breed. Animal Reproduction Science 110, 139-146.
Moore, R.K., Shimasaki, S., 2005. Molecular biology and physiological role of the oocyte factor, BMP-15. Molecular and Cellular Endocrinology 234, 67-73.
Muhaghegh Dolatabady, M., Habibizad, J., 2019. Single nucleotide polymorphisms (SNPs) of GDF9 gene in Bahmaei and Lak Ghashghaei sheep breeds and its association with litter size. Iranian Journal of Applied Animal Science 9, 427-432.
National Sheep Association. Sheep Breeders Round Table. Available at: https://www.nationalsheep.org.uk/sbrt/ (accessedon 3 February 2021).
Niu, Z.-G., Qin, J., Jiang, Y., Ding, X.D., Ding, Y.G., Tang, S., Shi, H.C., 2021. The identification of mutation in BMP15 gene associated with litter size in Xinjiang Cele Black Sheep. Animals 11, 668-677.
Otsuka, F., Shimasaki, S., 2002. A negative feedback system between oocyte bone morphogenetic protein 15 and granulosa cell kit ligand: its role in regulating granulosa cell mitosis. Proceedings of the National Academy of Sciences 99, 8060-8065.
Otsuka, F., Yao, Z., Lee, T.H., Yamamoto, S., Erickson, G.F., Shimasaki, S., 2000. Bone morphogenetic protein-15: identification of target cells and biological functions. Journal of Biological Chemistry 275, 39523-39528.
Piper, L., Bindon, B., 1982. The Booroola Merino and the performance of medium Non-Peppin crosses at Armidale [sheep breed; New South Wales].[Conference paper], Workshop on the Booroola Merino. Armidale, NSW (Australia).
Robertson, D., Foulds, L., Leversha, L., Morgan, F., Hearn, M., Burger, H., Wettenhall, R., De Kretser, D., 1985. Isolation of inhibin from bovine follicular fluid. Biochemical and Biophysical Research Communications 126, 220-226.
Rodgers, R.J., Stuchbery, S.J., Findlay, J.K., 1989. Inhibin mRNAs in ovine and bovine ovarian follicles and corpora lutea throughout the estrous cycle and gestation. Molecular and Cellular Endocrinology 62, 95-101.
Saleh, A.A., Hammoud, M., Dabour, N.A., Hafez, E., Sharaby, M.A., 2020. BMPR-1B, BMP-15 and GDF-9 genes structure and their relationship with litter size in six sheep breeds reared in Egypt. BMC Research Notes 13, 1-7.
Saneei D, Nejati-Javaremi, A., 2000. Litter size in Baluchi sheep is controlled by an over-dominant autosomal major gene. The 14th International Congress on Animal Reproduction, Sweden, 1154.
Suo, F., Liu, Y.B, Te, R., Qi, Y.X., He, X.L., Han, Y.S., 2012. Association of INHA and INHBA genes polymorphism with prolificacy of Bamei mutton sheep. Acta Agriculturae Boreali-Sinica 3, 119-128.
Tian, X., Sun, H., Wang, Y., 2010. Genetic polymorphism of INHA gene and its effect on litter size in three sheep breeds. Journal of Northwest A & F University-Natural Science Edition 38, 23-29.
Williams, G. L., Cardoso, R. C., 2021. Neuroendocrine control of estrus and oulation.In: R. M. Hopper (Ed.), Bovine Reproduction, John Wiley & Sons, Inc. New York, USA, pp. 269-291.
Woodruff, T.K., Besecke, L.M., Groome, N., Draper, L.B., Schwartz, N.B., Weiss, J., 1996. Inhibin A and inhibin B are inversely correlated to follicle-stimulating hormone, yet are discordant during the follicular phase of the rat estrous cycle, and inhibin A is expressed in a sexually dimorphic manner. Endocrinology 137, 5463-5467.
Zhou, W., Chu, M., Sun, S., Fang, L., Ye, S., 2007. A candidate gene INHA for prolificacy of small Tail Han sheep. Journal of Agricultural Biotechnology 15, 32-36.
Journal of Livestock Science and Technologies
Volume 10, Issue 2
December 2022
Pages 1-8

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