A meta-analysis study of the association between FecB polymorphism and litter size in sheep

Document Type : Original Research Article (Regular Paper)


Department of Animal Science, Faculty of Agriculture, University of Jiroft, Jiroft, Iran


In the current study, a meta-analysis was carried out by merging outcomes resulting from 26 published studies in various breeds of sheep to assess the influence of the FecB gene on litter size by applying the additive, recessive, dominant, and co-dominant genetic models. The model with random effects was used for data analysis according to the Cochran Q test and I2 quantity statistical measures. Standardized mean difference (SMD) was applied to measure the size effects of ' +' and B alleles of FecB on the litter size. The significant effect (P<0.01) of FecB genotypes on the litter size was identified under the additive (SMD = 0.511), dominant (SMD = 0.469) and recessive (SMD = 0.255) models. An increase in the litter size by approximately 0.47 lambs (Dominant model) was associated with the first copy of the FecB gene and 0.25 lambs (Recessive model) with the second copy of FecB. The findings of the current study supported the idea that BMPR1B would fundamentally influence the litter size in sheep. Subsequently, it may be utilized in marker-assisted selection programs to improve the genetic merit of litter size in the future. Introgression this gene through crossbreeding programs in low prolific breeds may improve reproductive performance.


Main Subjects

Ambike, V., Venkataramanan, R., Karthickeyan, S.M.K., and Tirumurugaan, K.G., 2022. Meta-analysis of performance and genetic parameter estimates for growth and body weight traits of sheep in the tropics. Small Ruminant Research 206, 106597.
Chen, X., Sun, H., Tian, S., Xiang, H., Zhou, L., Dun, W., Zhao, X., 2015. Increasing litter size in a sheep breed by marker-assisted selection of BMPR1B A746G mutation. Journal of Genetics 94, 139–142.
Chong, Y., Liu, G., Jiang, X., 2019. Effect of BMPRIB gene on litter size of sheep in China: A meta-analysis. Animal Reproduction Science 210, 106175.
Chu, M., Jia, L., Zhang, Y., Jin, M., Chen, H., Fang, L., Di, R., Cao, G., Feng, T., Tang, Q., 2011. Polymorphisms of coding region of BMPR-IB gene and their relationship with litter size in sheep. Molecular Biology Reports 38, 4071–4076.
Chu, M.X., Liu, Z.H., Jiao, C.L., He, Y.Q., Fang, L., Ye, S.C., Chen, G.H., Wang, J.Y., 2007. Mutations in BMPR-IB and BMP-15 genes are associated with litter size in Small Tailed Han sheep (Ovis aries). Journal of Animal Science 85, 598–603.
Cochran, W.G., 1954. The combination of estimates from different experiments. Biometrics 10, 101–129.
Cohen, J., 2013. Statistical power analysis for the behavioral sciences. 2nd ed. Routledge, New York, USA.
Davis, G.H., 2005. Major genes affecting ovulation rate in sheep. Genetics Selection Evolution 37, S11–S23.
Davis, G.H., Galloway, S.M., Ross, I.K., Gregan, S.M., Ward, J., Nimbkar, B. V., Ghalsasi, P.M., Nimbkar, C., Gray, G.D., Subandriyo, Inounu, I., Tiesnamurti, B., Martyniuk, E., Eythorsdottir, E., Mulsant, P., Lecerf, F., Hanrahan, J.P., Bradford, G.E., Wilson, T., 2002. DNA tests in prolific sheep from eight countries provide new evidence on origin of the Booroola (FecB) mutation. Biology of Reproduction 66, 1869–1874.
Dawson, D.V., Pihlstrom, B.L., Blanchette, D.R., 2016. Understanding and evaluating meta-analysis. The Journal of the American Dental Association 147, 264–270.
Debnath, J., Singh, R.V., 2014. Genetic polymorphism of boorola FecB gene and its association with litter size in Balangir, Shahabadi and Bonpala sheep breeds. Indian Journal of Animal Research 48, 307–314.
Delphino, B., Breno, V., Fernando, L., Pinto, B., 2021a. Meta-analysis of genetic parameters for economic traits in sheep. Livestock Science 247, 104477.
Delphino, B., Breno, V., Fernando, L., Pinto, B., 2021b. Meta-analysis of genetic parameters for economic traits in buffaloes. Livestock Science 251, 104614.
DerSimonian, R., Laird, N., 1986. Meta-analysis in clinical trials. Controlled Clinical Trials 7, 177–188.
Duval, S., Tweedie, R., 2000. Trim and fill: a simple funnel‐plot–based method of testing and adjusting for publication bias in meta‐analysis. Biometrics 56, 455–463.
Egger, M., Smith, G.D., Schneider, M., Minder, C., 1997. Bias in meta-analysis detected by a simple, graphical test. British Medical Journal 315, 629–634.
Fang, D., Wu, J., Xu, J., Luo, Y., Zhang, L., Wang, L., Yang, L., Lei, Z., 2010. Research on application effect in breeding of molecular marker in sheep BMPR-IB gene. Xinjiang Agricultural Sciences 47, 189–194.
Fogarty, N.M., 2009. A review of the effects of the Booroola gene (FecB) on sheep production. Small Ruminant Research 85, 75–84.
Guan, F., Liu, S.-R., Shi, G.-Q.,Yang, L.-G., 2007. Polymorphism of FecB gene in nine sheep breeds or strains and its effects on litter size, lamb growth and development. Animal Reproduction Science 99, 44–52.
Hatala, R., Keitz, S., Wyer, P., Guyatt, G., 2005. Tips for learners of evidence-based medicine: 4. Assessing heterogeneity of primary studies in systematic reviews and whether to combine their results. Canadian Medical Association Journal 172, 661–665.
Hernandez H, D., Montes V, D., De la Ossa V, J., 2019. Association of the FecB polymorphism with the natural prolificacy of the Colombian Hair Sheep. Revista MVZ Córdoba 25, 1–6.
Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J., Welch, V.A., 2019. Cochrane handbook for systematic reviews of interventions. 2nd ed. Chichester, UK, John Wiley & Sons.
Higgins, J.P.T., Thompson, S.G., Deeks, J.J., Altman, D.G., 2003. Measuring inconsistency in meta-analyses. British Medical Journal 327, 557–560.
Hossein-zadeh, N.G., 2021. A meta-analysis of heritability estimates for milk fatty acids and their genetic relationship with milk production traits in dairy cows using a random-effects model. Livestock Science 244, 104388.
Hua, G.H., Yang, L.G., 2009. A review of research progress of FecB gene in Chinese breeds of sheep. Animal Reproduction Science 116, 1–9.
Hua, G.H., Chen, S.L., Ai, J.T., Yang, L.G., 2008. None of polymorphism of ovine fecundity major genes FecB and FecX was tested in goat. Animal Reproduction Science 108, 279–286.
Hunter, J.E., Schmidt, F.L., 2004. Methods of meta-analysis: Correcting error and bias in research findings. 2nd ed. Thousand Oaks, CA, SAGE Publication.
Jia, C., Li, N., Zhao, X., Zhu, X., Jia, Z., 2005. Association of single nucleotide polymorphisms in exon 6 region of BMPRIB gene with litter size traits in sheep. Asian-Australasian Journal of Animal Sciences 18, 1375–1378.
Joober, R., Schmitz, N., Annable, L., Boksa, P., 2012. Publication bias: what are the challenges and can they be overcome?. Journal of Psychiatry and Neuroscience 37, 149.
Kang, X.L., Liu, J.L., Liu, Y.Q., Wang, S.Y.,Feng, D.Z., 2017. Association between BMPR-IB polymorphism and litter size in two sheep groups. Acta Agriculturae Boreali-Occidentalis Sinica 26, 497–502.
Kumar, S., Mishra, A.K., Kolte, A.P., Dash, S.K., Karim, S.A., 2008. Screening for Booroola (FecB) and Galway (FecXG) mutations in Indian sheep. Small Ruminant Research 80, 57–61.
Lee, Y., 2015. Meta-analysis of genetic association studies. Annals of Laboratory Medicine 35, 283.
Li, D., Sun, W., Ni, R., Zhang, X.N., Zhang, Y.L., Chu, M.X., Zhang, Y.F., Shen, G.Z., Chen, L., Wu, W.Z., 2012. Genetic diversity of FecB gene and association analysis of its litter size. Journal of Animal Science and Veterinary Medicine 31, 1–5.
Li, H., Xu, H., Akhatayeva, Z., Liu, H., Lin, C., Han, X., Lu, X., Lan, X., Zhang, Q., Pan, C., 2021. Novel indel variations of the sheep FecB gene and their effects on litter size. Gene 767, 145176.
Mahdavi, M., Nanekarani, S., Hosseini, S.D., 2014. Mutation in BMPR-IB gene is associated with litter size in Iranian Kalehkoohi sheep. Animal Reproduction Science 147, 93–98.
Mahmoudi, P., Rashidi, A., Rostamzadeh, J., Razmkabir, M., 2019. Association between c . 1189G > A single nucleotide polymorphism of GDF9 gene and litter size in goats : A meta-analysis. Animal Reproduction Science 209, 106140.
Mahmoudi, P., Rostamzadeh, J., Rashidi, A., Zergani, E., Razmkabir, M., 2020. A meta-analysis on association between CSN3 gene variants and milk yield and composition in cattle. Animal Genetics 51, 369–381.
Maskur, M., Tapaul, R., Kasip, L., 2016. Genetic polymorphism of bone morphogenetic protein receptor 1B (BMPR-1B) gene and its association with litter size in Indonesian fat-tailed sheep. African Journal of Biotechnology 15, 1315–1319.
Mathur, M.B., VanderWeele, T.J., 2020. Sensitivity analysis for publication bias in meta‐analyses. Journal of the Royal Statistical Society 69, 1091–1119.
Minelli, C., Thompson, J.R., Abrams, K.R., Thakkinstian, A., Attia, J., 2005. The choice of a genetic model in the meta-analysis of molecular association studies. International Journal of Epidemiology 34, 1319–1328.
Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., Group, P., 2009. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Medicine 6, e1000097.
Mulsant, P., Lecerf, F., Fabre, S., Schibler, L., Monget, P., Lanneluc, I., Pisselet, C., Riquet, J., Monniaux, D., Callebaut, I., Cribiu, E., Thimonier, J., Teyssier, J., Bodin, L., Cognié, Y., Chitour, N., Elsen, J.M., 2001. Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Mérino ewes. Proceedings of the National Academy of Sciences, USA 98, 5104–5109.
Pan, Z.Y., Di, R., Tang, Q.Q., Jin, H.H., Chu, M.X., Huang, D.W., He, J.N., Liu, Q.Y., Hu, W.P., Wang, X.Y., Yao, Y.X., Liu, L., Song, C.L., 2015. Tissue-specific mRNA expression profiles of GDF9 , BMP15 , and BMPR1B genes in prolific and non-prolific goat breeds, Czech Journal of Animal Science 10, 452–458.
Peters, J.L., Sutton, A.J., Jones, D.R., Abrams, K.R., Rushton, L., 2008. Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. Journal of Clinical Epidemiology 61, 991–996.
Plakkot, B., Mohanan, A., Kanakkaparambil, R., 2020. Prolificacy in small ruminants. Journal of Dairy, Veterinary and Animal Research 9, 85–90.
Potki, P., Mirhoseini, S.Z., Afraz, F., Vahidi, S.M.F., 2020. A profile of single nucleotide polymorphisms in fecundity genes among Iranian sheep breeds by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Iranian Journal of Applied Animal Science 10, 265–285.
R Development Core Team, 2022. R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria.
Razmkabir, M., Mahmoudi, P., Rashidi, A., Rostamzadeh, J., Idrees, S., 2021.  Effect of BLG gene variants on milk-related traits in small ruminants: a meta-analysis. Italian Journal of Animal Science 20, 1410–1422.
Ren, Y.L., Shen, Z.Q., LI, M., Xiao, N., Dong, W.Y., Li, J.L., Wang, J.J., 2011. Association of polymorphisms in the FecB gene with litter size in Wadi sheep. China Animal Husbandry and Veterinary Medicine 38, 159–162.
Roy, J., Polley, S., De, S., Mukherjee, A., Batabyal, S., Pan, S., Brahma, B., Datta, T.K., Goswami, S.L., 2011. Polymorphism of fecundity genes (FecB, FecX, and FecG) in the Indian Bonpala sheep. Animal Biotechnology 22, 151–162.
Shao, Y.G., Mirinisahan, K., Liu, W.J., 2012. Study on the relationship between the polymorphism of BMPR-IB gene and litter size in Xinjiang Cele Black sheep. China Animal Husbandry and Veterinary Medicine 39, 221-223.
Sharma, R.C., Gowane, G.R., Kumar, R., Kumar, A., Misra, S.S., Mallick, P.K., 2022. Production evaluation of Booroola fecundity (FecB) gene introgressed Avishaan sheep in semi-arid tropics of India. Small Ruminant Research 106720.
Shi, H.C., Niu, Z.G., Bai, J., Feng, L.J., Mu, M.R.S., Yang, Q.Y., Liu, M.J., Jia, F., 2012. Effect on litter size of Cele black sheep and genetic regularity of BMPR-IB gene mutation. China Journal of Animal Science 38, 14–17.
Singh, P., Deepak, S., SatyendraPal, S., 2020. Absence of polymorphism in Booroola (FecB) gene in Indian Muzzafarnagari sheep breed. Journal of Animal Research 10, 30954.
Souza, C.J.H., MacDougall, C., Campbell, B.K., McNeilly, A.S., Baird, D.T., 2001. The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPR1B) gene. Journal of Endocrinology 169, 3–8.
Sterne, J.A.C., Sutton, A.J., Ioannidis, J.P.A., Terrin, N., Jones, D.R., Lau, J., Carpenter, J., Rücker, G., Harbord, R.M., Schmid, C.H., 2011. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. British Medical Journal 342, d4002.
Sun, H.X., Dun, W.T., Chen, X.Y., Tian, S.J., Tan, W., 2011. Relationship between polymorphism of BMPR-IB gene and litter size and sexual season for different sheep breeds. Hunan Agricultural Sciences Technology 3. 147-149.
Sutton, A.J., Abrams, K.R., Jones, D.R., Sheldon, T.A., Song, F., 2000. Methods for meta-analysis in medical research. Chichester, England, John Wiley & Sons.
Tian, X., Sun, H., Wang, Y., 2009. Genetic polymorphism of BMPR-IB gene and effect on litter size in three sheep breeds. Journal of Northwest University (Natural Science Edition) 37, 31–36.
Viechtbauer, W., 2010. Conducting meta-analyses in R with the metafor package. Journal of Statistical Software 3, 1–48.
Wang, W., La, Y., Zhou, X., Zhang, X., Li, F., Liu, B., 2018. The genetic polymorphisms of TGFβ superfamily genes are associated with litter size in a Chinese indigenous sheep breed (Hu sheep). Animal Reproduction Science 189, 19–29.
Wang, W., Liu, S., Li, F., Pan, X., Li, C., Zhang, X., Ma, Y., La, Y., Xi, R., Li, T., 2015. Polymorphisms of the ovine BMPR-IB, BMP-15 and FSHR and their associations with litter size in two Chinese indigenous sheep breeds. International Journal of Molecular Sciences 16, 11385–11397.
Wang, X., Maimaitiyiming, B., 2011. Studies of BMPR-IB gene as a candidate gene for prolificacy in Duolang sheep. Xinjiang Agricultural Sciences 47, 1813–1818.
Wilson, T., Wu, X.Y., Juengel, J.L., Ross, I.K., Lumsden, J.M., Lord, E.A., Dodds, K.G., Walling, G.A., McEwan, J.C., O’Connell, A.R., McNatty, K.P., Montgomery, G.W., 2001. Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biology of Reproduction 64, 1225–1235.
Yang, Y., Feng, T., Chu, M., Yun, P., Xiao, W., Xue, Z., Zhang, J., Meng, D., 2012. FecB mutation of BMPR-IB gene and its association with litter size and growth traits in Small Tailed Han sheep. Acta Agriculturae Boreali-Occidentalis Sinica 27, 38–43.
Yang, H., Yang, Y., Liu, S., Zhong, F., Zhang, Y., He, Q., 2010. Analysis of Single Nucleotide Polymorphism of BMPR-IB Gene in Sheep. Acta Agriculturae Boreali-Occidentalis Sinica 19, 7-11.
Zhu, E.Y., Shi, H.C., Wu, J., Liu, M.J., Jian, Z.J., Bai, J., Xu, X.M., 2006. Study on bone morphogenetic protein receptor IB as a candidate gene for prolificacy in sheep. Acta Agriculturae Boreali-Occidentalis Sinica 15, 20–30.