Jianlei JIA, Dejuan XIE, Yingying ZHANG, Huaixia ZHANG, Liping ZHANG, Shengzhen HOU, Qian CHEN

Association of BMPR-1B Gene 3’-UTR Region Polymorphism with Litter Size in Tibetan Sheep

Bone Morphogenetic Protein Receptor-1B (BMPR-1B) is considered as the primary gene in sheep for follicular development and litter size trait. Ithas been defi ned as the most major candidate gene for genetic markers of sheep reproductive performance. In our study, polymorphisms in theBMPR-1B gene 3’-UTR region were investigated in 363 Tibetan sheep (119 Plateau-type Tibetan sheep, 141 Valley-type Tibetan sheep, and 103Oula-type Tibetan sheep) by DNA sequencing analysis. Two single nucleotide polymorphisms (SNPs) were identifi ed, which were G1339A andA1354G. The frequencies of SNPs were in Hardy-Weinberg equilibrium (Chi-square test, P>0.05). AA and AG genotypes were found in the A1354Gvariant of the 3’UTR region, that AA and A were the preponderant genotype and allele, respectively. The χ2 independence test analyses indicatedthat the A1354G variant of BMPR-1B gene 3’UTR region polymorphisms was signifi cantly correlated with litter size in all-types Tibetan sheep (P

Tibet Koyunlarında BMPR-1B Geni 3’-UTR Bölgesi Polimorfizmi İle Batın Genişliği İlişkisi

Kemik Morfogenetik Protein Reseptörü-1B (BMPR-1B), koyunlarda foliküler gelişim ve batın genişliği özelliği için birincil gen olarak kabul edilir. Bu gen, koyunlarda üreme performansının genetik belirteçleri için en önemli aday gen olarak tanımlanmıştır. Çalışmamızda, 363 Tibet koyununda (119 plato tipi Tibet koyunu, 141 vadi tipi Tibet koyunu ve 103 Oula tipi Tibet koyunu) BMPR-1B geninin 3’-UTR bölgesindeki polimorfi zmler DNA dizi analizi ile araştırıldı. G1339A ve A1354G adlı iki single nükleotid polimorfi zm (SNP) saptandı. SNP’lerin frekansları Hardy-Weinberg dengesi içerisindeydi (Ki-kare testi, P>0.05). 3’UTR bölgesinin A1354G varyantında AA ve AG genotipleri saptandı ve AA ve A sırasıyla baskın genotip ve aleldi. χ2 bağımsızlık testi analizleri, BMPR-1B geni 3’UTR bölgesi polimorfi zmlerinden A1354G varyantının, tüm Tibet koyun türlerinde batın genişliği ile yakından ilişkili olduğunu gösterdi (P

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1. Jia JL, Chen Q, Gui LS, Jin JP, Li YY, Ru QH, Hou SZ: Association of polymorphisms in bone morphogenetic protein receptor-1B gene exon9 with litter size in Dorset, Mongolian, and Small Tail Han ewes. Asian Australas J Anim Sci, 32 (7): 949-955, 2019. DOI: 10.5713/ajas.18.0541

2. Zhang XM, Li WR, Wu YS, Peng XR, Lou B, Wang LQ, Liu MJ: Disruption of the sheep BMPR-1B gene by CRISPR/Cas9 in in vitroproduced embryos. Theriogenology, 91, 163-172.e2, 2017. DOI: 10.1016/j. theriogenology.2016.10.025

3. Jia JL, Jin JP, Chen Q, Yuan Z, Li HQ, Bian JH, Gui LS: Eukaryotic expression, Co-IP and MS identify BMPR-1B protein-protein interaction network. Biol Res, 53:24, 2020. DOI: 10.1186/s40659-020-00290-7

4. Ahlawat S, Sharma R, Maitra A, Tantia MS: Current status of molecular genetics research of goat fecundity. Small Ruminant Res, 125, 34-42, 2015. DOI: 10.1016/j.smallrumres.2015.01.027

5. Maskur M, Tapaul R, Kasip L: Genetic polymorphism of bone morphogenetic protein receptor 1B (BMPR-1B) gene and its association with litter size in Indonesian fat-tailed sheep. Afr J Biotechnol, 15, 1315- 1319, 2016. DOI: 10.5897/AJB2015.15093

6. Carreira AC, Alves GG, Zambuzzi WF, Sogayar MC, Granjeiro JM: Bone morphogenetic proteins: Structure, biological function and therapeutic applications. Arch Biochem Biophys, 561, 64-73, 2014. DOI: 10.1016/j.abb.2014.07.011

7. Polley S, De S, Batabyal S, Kaushik R, Yadav P, Arora JS, Chattopadhyay S, Pan S, Brahma B, Datta TW, Goswami SL: Polymorphism of fecundity genes (BMPR1B, BMP15 and GDF9) in the Indian prolific Black Bengal goat. Small Ruminant Res, 85, 122-129, 2009. DOI: 10.1016/j.smallrumres.2009.08.004

8. Crispo M, Vilariño M, Santos-Neto PC, Nunez-Olivera R, Cuadro F, Barrera N, Mulet AP, Nguyen TH, Anegon I, Menchaca A: Embryo development, fetal growth and postnatal phenotype of eGFP lambs generated by lentiviral transgenesis. Transgenic Res, 24, 31-41, 2015. DOI: 10.1007/s11248-014-9816-x

9. Zhou JW, Guo YM, Kang JP, Degen AA, Titgemeyer EC, Jing XP, Wang WJ, Shang ZH, Li ZP, Yang G, Long RJ: Tibetan sheep require less energy intake than small-tailed Han sheep for N balance when offered a low protein diet. Anim Feed Sci Technol, 248, 85-94, 2019. DOI: 10.1016/j. anifeedsci.2019.01.006

10. Nei M: Estimation of average heterozygosity and genetic distance from a small number of individuals. Genetics, 89 (3): 583-590, 1978.

11. Lin Y, Jiang WG: Bone morphogenetic proteins in tumour associated angiogenesis and implication in cancer therapies. Cancer Lett, 380, 586- 597, 2016. DOI: 10.1016/j.canlet.2015.10.036

12. Jia JL, Zhang LP, Ding Q, Yang ZW: Correlation between polymorphism of BMPR-1B gene exon7 and lambing performance of sheep. JNWAFU, 44 (1): 7-13, 2016. DOI: 10.13207/j.cnki.jnwafu.2016.01.002

13. Du L, Zhang LP, Zhang XY, Zhu SH, Ma XM. The Correlation analysis between polymorphism and fecundity of 1113 locus in BMPR-1B gene CDS area of three sheep (Ovis aries) varieties. J Agric Biotechnol, 25 (12): 1989-1997, 2017.

14. Ma XM, Zhang LP, Zhu SH, Di L, Zhang XY. Analysis of polymorphism at 864 locus of BMPR-1B gene CDS region and its relationship with litter size in four sheep breeds. GAB, 36 (10): 4116-4124, 2017. DOI: 10.13417/j. gab.036.004116

15. Zhu SH, Zhang LP, Ma XM, Di L, Zhang XY: Analysis and differences of sheep BMP-15 gene expression in ewes with different lambing traits. Genomics Appl Biol, 37 (05): 1853-1858, 2018. DOI: 10.13417/j. gab.037.001853

16. Zhao YZ: Application of quantitative genetics in sheep breeding. In, Chinese Sheep Science. 384, China Agriculture Press, Beijing, 2013.

17. Chen CY, Chen ST, Juan HF, Huang HC: Lengthening of 3’ UTR increases with morphological complexity in animal evolution. Bioinformatics, 28, 3178-3181, 2012. DOI: 10.1093/bioinformatics/bts623

18. Berkovits BD, Mayr C: Alternative 3’ UTRs act as scaffolds to regulate membrane protein localization. Nature, 522, 363-367, 2015. DOI: 10.1038/ nature14321

19. Mayr C: What are 3’ UTRs doing. Cold Spring Harb Perspect Biol, 11:a034728, 2018. DOI: 10.1101/cshperspect.a034728

20. Chu MX, Jia LH, Zhang YJ, Jin M, Chen HQ, Fang L, Di R, Cao GL, Feng T, Tang QQ, Ma HY, Li K: Polymorphisms of coding region of BMPR1B gene and their relationship with litter size in sheep. Mol Biol Rep, 38, 4071-4076, 2011. DOI: 10.1007/s11033-010-0526-z

21. Liu HJ, Xu TW, XU SX, Ma L, Han XP, Wang XG, Zhang XL, Hu LY, Zhao N, Chen YW, Pi L, Zhao XQ: Effect of dietary concentrate to forage ratio on growth performance, rumen fermentation and bacterial diversity of Tibetan sheep under barn feeding on the Qinghai-Tibetan plateau. PeerJ, 7:e7462, 2019. DOI: 10.7717/peerj.7462

22. Chu MX, Zhao XH, Zhang YJ, Jin M, Wang JY, Di R, Cao GL, Feng T, Fang L, Ma YH, Li K: Polymorphisms of BMPR-1B gene and their relationship with litter size in goats. Mol Biol Rep, 37 (8): 4033-4039, 2010. DOI: 10.1007/s11033-010-0062-x

23. Mu FF, Wang X, Xu WJ, Liu EY, Ci RQZ, Zhang L: Correlation between BMP15 and BMPR-IB gene mutations in Pengbo semi-fine wool sheep and their lambing. Journal of Huaibei Normal University (Natural Sciences), 40 (3): 49-54, 2019. DOI: 10.3969/j.issn.2095-0691.2019.03.010

24. Antebi YE, Linton JM, Klumpe H, Bintu B, Gong M, Su C, McCardell R, Elowitz MB: Combinatorial signal perception in the bmp pathway. Cell, 170, 1184-1196, 2017. DOI: 10.1016/j.cell.2017.08.015