EXPLORING MUTATIONS IN THE GDF9 GENE FOR ENHANCED PROLIFICACY THROUGH BIOINFORMATICS ANALYSIS
Main Article Content
Keywords
GDF9, Mutations, Reproductive Traits
Abstract
This study comprehensively investigated sixteen mutations within the GDF9 gene in goats (Capra hircus), shedding light on their potential implications for goat reproduction. Utilizing bioinformatics tools, we analyzed the physicochemical properties, structural alterations, protein-protein interactions, and Gene Ontology (GO) associated with these mutations. The results revealed variations in molecular weight, instability index, and other physicochemical characteristics among the mutated GDF9 sequences. Structural modeling demonstrated subtle changes in functional domains induced by specific mutations. Protein-protein interaction network analysis unveiled close associations between GDF9 and key reproductive genes, emphasizing its central role in fertility. The study provides crucial insights for molecular breeding strategies aimed at enhancing goat prolificacy and reproductive performance. Understanding the genetic factors influencing goat reproduction is pivotal for developing targeted breeding approaches, ultimately contributing to sustainable and efficient livestock production. This research contributes to the growing body of knowledge surrounding the GDF9 gene in goats, offering a foundation for further exploration and practical applications in improving goat reproductive traits through molecular breeding.
References
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[29] Shaha M, Miah G, Lima A, Miazi OF, Gupta MD and Das A. Identification of polymorphisms in GDF9 and BMP15 genes in Jamunapari and crossbred goats in Bangladesh. Tropical Animal Health and Production 2022; 54: 350.
[30] Wang X, Yang Q, Wang K, Yan H, Pan C, Chen H, Liu J, Zhu H, Qu L and Lan X. Two strongly linked single nucleotide polymorphisms (Q320P and V397I) in GDF9 gene are associated with litter size in cashmere goats. Theriogenology 2019; 125: 115-121.
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[33] Wang Y, Zhang X and Chu M. Polymorphisms of caprine GDF9 gene and their association with litter size in Henan dairy goat. J. Anim. Vet. Adv 2013; 12: 1590-1596.
[34] Yang C, Zi X, Wang Y, Yang D, Ma L, Lu J, Niu H and Xiao X. Cloning and mRNA expression levels of GDF9, BMP15, and BMPR1 B genes in prolific and non-prolific goat breeds. Molecular Reproduction and Development 2012; 79:
[35] Wouobeng P, Kouam JS, Meutchieye F, Yacouba M, Achieng G, Tutah J, Mutai C and Agaba M. Polymorphism of Prolificacy Genes (BMP15, BMPR 1B and GDF9), in the Native Goat (Capra hircus) of Cameroon. Genetics & Biodiversity Journal 2020; 4: 28-43.
[36] Hadizadeh M, Mohammadbadi MR, Niazi A, Esmailizadeh A and Gazooei YM. Search for polymorphism in growth and differentiation factor 9 (GDF9) gene in prolific beetal and tali goats (Capra hircus). Journal of Biodiversity and Environmental Sciences 2014; 4: 186-191.
[37]
[38] Wang B, Zhang Q, Xu J, Chen M, Liu K, Li Z and Pan Q. Polymorphism detection of GDF9 gene exon 2 in three China goat breeds. China Herbiv. Sci. Collect. Pap 2014; 1: 132-136.
[39] Tang J, Zhang W, Zhu D, Hui W, Su S and Chen S. Effects of GDF9 gene polymorphisms on serum levels of FSH and LH in goat ewes. Anim. Husb. Vet. Med 2017; 49: 13-18.
[40] Chu M, Wu Z, Feng T, Cao G, Fang L, Di R, Huang D, Li X and Li N. Polymorphism of GDF 9 gene and its association with litter size in goats. Veterinary research communications 2011; 35: 329-336.
[41] Dutta R, Das B, Laskar S, Kalita D, Borah P, Zaman G and Saikia D. Polymorphism, sequencing and phylogenetic characterization of growth differentiation factor 9 (GDF9) gene in Assam Hill goat. African Journal of Biotechnology 2013; 12: 6894.
[42] Ahlawat S, Sharma R, Roy M, Tantia M and Prakash V. Association analysis of novel SNPs in BMPR1B, BMP15 and GDF9 genes with reproductive traits in Black Bengal goats. Small Ruminant Research 2015; 132: 92-98.
[43] Loewe L. Genetic mutation. Nature education 2008; 1: 113.
[44] Wang F, Chu M, Pan L, Wang X, He X, Zhang R, Tao L, La Y, Ma L and Di R. Polymorphism detection of GDF9 gene and its association with litter size in Luzhong mutton sheep (Ovis aries). Animals 2021; 11: 571.
[45] Knight PG and Glister C. TGF-β superfamily members and ovarian follicle development. Reproduction 2006; 132: 191-206.
[46] Chu M, Jiao C, He Y, Wang J, Liu Z and Chen G. Association between PCR-SSCP of bone morphogenetic protein 15 gene and prolificacy in Jining Grey goats. Animal biotechnology 2007; 18: 263-274.
[47] Pourali Dogaheh S, Mirhoseini SZ, Tufarelli V, Hossein-Zadeh NG, Badbarin S, Colonna MA, Seidavi A and Selvaggi M. Investigating the polymorphism of bone morphogenetic protein receptor-1B (BMPR1B) gene in Markhoz goat breed. Animals 2020; 10: 1582.
[2] Mirzaei F. Effect of herbal feed additives on performance parameters of ruminants and especially on dairy goat: a review. 2013;
[3] MacHugh DE and Bradley DG. Livestock genetic origins: goats buck the trend. Proceedings of the National Academy of Sciences 2001; 98: 5382-5384.
[4] Aziz MA. Present status of the world goat populations and their productivity. World 2010; 861: 1.
[5] Skapetas B and Bampidis V. Goat production in the World: present situation and trends. Livestock research for Rural development 2016; 28: 200.
[6] Rischkowsky B, Pilling D and Scherf B. Status of animal genetic resources. Part 2007; 1: 23-49.
[7] Nazeer M and Shah SH. Morphological characterization of indigenous goats breeds of Khyber Pakhtunkhwa, Pakistan. Sarhad J Agric 2018; 34: 258-267.
[8] Sikandar A and Nasir A. Alimentary System of Native Goat Breeds of Pakistan. In: editors. Animal Science Annual Volume 2023. IntechOpen; 2023. p.
[9] Iqbal A, Khan B, Tariq M, Singh US-CTT, Mirza M and Singh T. Goat-A potential dairy animal: present and future prospects. Pakistan Journal of Agricultural Sciences (Pakistan) 2008; 45:
[10] Ali A and Afzal M. Genetic evaluation of Beetal goats for performance traits in Pakistan. A PhD Thesis. University of Agriculture, Faisalabad 2006;
[11] Moradband F, Rahimi G and Gholizadeh M. Association of polymorphisms in fecundity genes of GDF9, BMP15 and BMP15-1B with litter size in Iranian Baluchi sheep. Asian-Australasian journal of animal sciences 2011; 24: 1179-1183.
[12] Liao WX, Moore RK and Shimasaki S. Functional and molecular characterization of naturally occurring mutations in the oocyte-secreted factors bone morphogenetic protein-15 and growth and differentiation factor-9. Journal of Biological Chemistry 2004; 279: 17391-17396.
[13] Rumanta M, Kunda RM, Volkandari SD and Munir IM. Impact of Environmental Geographic toward Point Mutations in Exon 1 of Growth Differentiation Factor (GDF9) Gene in Kosta and Lakor Goat Breeds. Jurnal Penelitian Pendidikan IPA 2023; 9: 4813-4819.
[14] Hanrahan JP, Gregan SM, Mulsant P, Mullen M, Davis GH, Powell R and Galloway SM. 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 2004; 70: 900-909.
[15] Khazraji WJA, AL-Khuzai HM and AL-Shaikh MA. ANALYSIS OF GENETIC VARIANCE FOR MILK PRODUCTION AND IT COMPONENTS IN LOCAL GOAT FOR PROLACTIN RECEPTOR GENE. Diyala Agricultural Sciences Journal 2020; 12: 83-88.
[16] Knight PG and Glister C. Local roles of TGF-β superfamily members in the control of ovarian follicle development. Animal reproduction science 2003; 78: 165-183.
[17] Otsuka F, McTavish KJ and Shimasaki S. Integral role of GDF‐9 and BMP‐15 in ovarian function. Molecular reproduction and development 2011; 78: 9-21.
[18] Ghoreishi H, Fathi-Yosefabad S, Shayegh J and Barzegari A. Identification of mutations in BMP15 and GDF9 genes associated with prolificacy of Markhoz goats. Archives animal breeding 2019; 62: 565-570.
[19] Das A, Shaha M, Gupta MD, Dutta A and Miazi OF. Polymorphism of fecundity genes (BMP15 and GDF9) and their association with litter size in Bangladeshi prolific Black Bengal goat. Tropical Animal Health and Production 2021; 53: 1-8.
[20] Nicol L, Bishop SC, Pong-Wong R, Bendixen C, Holm L-E, Rhind SM and McNeilly AS. Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep. Reproduction 2009; 138: 921.
[21] Silva B, Castro E, Souza C, Paiva S, Sartori R, Franco M, Azevedo H, Silva T, Vieira A and Neves J. A new polymorphism in the Growth and Differentiation Factor 9 (GDF9) gene is associated with increased ovulation rate and prolificacy in homozygous sheep. Animal genetics 2011; 42: 89-92.
[22]
[23] Aboelhassan DM, Darwish AM, Ali NI, Ghaly IS and Farag IM. A study on mutation points of GDF9 gene and their association with prolificacy in Egyptian small ruminants. Journal of Genetic Engineering and Biotechnology 2021; 19: 1-11.
[24] Sherman BT, Hao M, Qiu J, Jiao X, Baseler MW, Lane HC, Imamichi T and Chang W. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res 2022; 50: W216-W221.
[25] Wang X, Yang Q, Zhang S, Zhang X, Pan C, Chen H, Zhu H and Lan X. Genetic effects of single nucleotide polymorphisms in the goat GDF9 gene on prolificacy: True or false positive? Animals 2019; 9: 886.
[26]
[27] Bi Y, Li J, Wang X, He L, Lan K, Qu L, Lan X, Song X and Pan C. Two novel rare strongly linked missense SNPs (P27R and A85G) within the GDF9 gene were significantly associated with litter size in Shaanbei white cashmere (SBWC) goats. Frontiers in Veterinary Science 2020; 7: 406.
[28] Dong C and Du L. Research on polymorphism analysis of GDF9 gene related to reproduction trait of goat. J. Shandong Agric. Univ.(Nat. Sci. Ed.) 2011; 42: 227-237.
[29] Shaha M, Miah G, Lima A, Miazi OF, Gupta MD and Das A. Identification of polymorphisms in GDF9 and BMP15 genes in Jamunapari and crossbred goats in Bangladesh. Tropical Animal Health and Production 2022; 54: 350.
[30] Wang X, Yang Q, Wang K, Yan H, Pan C, Chen H, Liu J, Zhu H, Qu L and Lan X. Two strongly linked single nucleotide polymorphisms (Q320P and V397I) in GDF9 gene are associated with litter size in cashmere goats. Theriogenology 2019; 125: 115-121.
[31]
[32] Zhao J, Liu S, Zhou X, Zhang R, Li Y, Wang X and Chen Y. A non‐synonymous mutation in GDF 9 is highly associated with litter size in cashmere goats. Animal Genetics 2016; 47: 630-631.
[33] Wang Y, Zhang X and Chu M. Polymorphisms of caprine GDF9 gene and their association with litter size in Henan dairy goat. J. Anim. Vet. Adv 2013; 12: 1590-1596.
[34] Yang C, Zi X, Wang Y, Yang D, Ma L, Lu J, Niu H and Xiao X. Cloning and mRNA expression levels of GDF9, BMP15, and BMPR1 B genes in prolific and non-prolific goat breeds. Molecular Reproduction and Development 2012; 79:
[35] Wouobeng P, Kouam JS, Meutchieye F, Yacouba M, Achieng G, Tutah J, Mutai C and Agaba M. Polymorphism of Prolificacy Genes (BMP15, BMPR 1B and GDF9), in the Native Goat (Capra hircus) of Cameroon. Genetics & Biodiversity Journal 2020; 4: 28-43.
[36] Hadizadeh M, Mohammadbadi MR, Niazi A, Esmailizadeh A and Gazooei YM. Search for polymorphism in growth and differentiation factor 9 (GDF9) gene in prolific beetal and tali goats (Capra hircus). Journal of Biodiversity and Environmental Sciences 2014; 4: 186-191.
[37]
[38] Wang B, Zhang Q, Xu J, Chen M, Liu K, Li Z and Pan Q. Polymorphism detection of GDF9 gene exon 2 in three China goat breeds. China Herbiv. Sci. Collect. Pap 2014; 1: 132-136.
[39] Tang J, Zhang W, Zhu D, Hui W, Su S and Chen S. Effects of GDF9 gene polymorphisms on serum levels of FSH and LH in goat ewes. Anim. Husb. Vet. Med 2017; 49: 13-18.
[40] Chu M, Wu Z, Feng T, Cao G, Fang L, Di R, Huang D, Li X and Li N. Polymorphism of GDF 9 gene and its association with litter size in goats. Veterinary research communications 2011; 35: 329-336.
[41] Dutta R, Das B, Laskar S, Kalita D, Borah P, Zaman G and Saikia D. Polymorphism, sequencing and phylogenetic characterization of growth differentiation factor 9 (GDF9) gene in Assam Hill goat. African Journal of Biotechnology 2013; 12: 6894.
[42] Ahlawat S, Sharma R, Roy M, Tantia M and Prakash V. Association analysis of novel SNPs in BMPR1B, BMP15 and GDF9 genes with reproductive traits in Black Bengal goats. Small Ruminant Research 2015; 132: 92-98.
[43] Loewe L. Genetic mutation. Nature education 2008; 1: 113.
[44] Wang F, Chu M, Pan L, Wang X, He X, Zhang R, Tao L, La Y, Ma L and Di R. Polymorphism detection of GDF9 gene and its association with litter size in Luzhong mutton sheep (Ovis aries). Animals 2021; 11: 571.
[45] Knight PG and Glister C. TGF-β superfamily members and ovarian follicle development. Reproduction 2006; 132: 191-206.
[46] Chu M, Jiao C, He Y, Wang J, Liu Z and Chen G. Association between PCR-SSCP of bone morphogenetic protein 15 gene and prolificacy in Jining Grey goats. Animal biotechnology 2007; 18: 263-274.
[47] Pourali Dogaheh S, Mirhoseini SZ, Tufarelli V, Hossein-Zadeh NG, Badbarin S, Colonna MA, Seidavi A and Selvaggi M. Investigating the polymorphism of bone morphogenetic protein receptor-1B (BMPR1B) gene in Markhoz goat breed. Animals 2020; 10: 1582.
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Mar 2, 2024
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Saba Saeed, Shakeela Parveen, Muhammad Amir Iqbal, Jawaria Farooq, & Amreen Naz. (2024). EXPLORING MUTATIONS IN THE GDF9 GENE FOR ENHANCED PROLIFICACY THROUGH BIOINFORMATICS ANALYSIS. Journal of Population Therapeutics and Clinical Pharmacology, 31(3), 17–26. https://doi.org/10.53555/jptcp.v31i3.4711
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Author Biographies
Saba Saeed
Department of Zoology, The Government Sadiq College Women University, 63100, Bahawalpur, Punjab, Pakistan.
Shakeela Parveen
Department of Zoology, The Government Sadiq College Women University, 63100, Bahawalpur, Punjab, Pakistan.
Muhammad Amir Iqbal
Institute of Zoology, University of the Punjab, Lahore, Punjab, Pakistan.
Jawaria Farooq
Department of Zoology, The Government Sadiq College Women University, 63100, Bahawalpur, Punjab, Pakistan.
Amreen Naz
Department of Zoology, The Government Sadiq College Women University, 63100, Bahawalpur, Punjab, Pakistan.