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Association analysis of SSTR2 copy number variation with cattle stature and its expression analysis in Chinese beef cattle

  • J. Cheng (a1), R. Jiang (a1), X. K. Cao (a1), M. Liu (a1), Y. Z. Huang (a1), X. Y. Lan (a1), H. Cao (a2), C. Z. Lei (a1) and H. Chen (a1)...


Copy number variations (CNVs), as an important source of genetic variation, can affect a wide range of phenotypes by diverse mechanisms. The somatostatin receptor 2 (SSTR2) gene plays important roles in cell proliferation and apoptosis. Recently, this gene was mapped to a CNV region, which encompasses quantitative trait loci of cattle economic traits including body weight, marbling score, etc. Therefore, SSTR2 CNV may exhibit phenotypic effects on cattle growth traits. In the current study, distribution of SSTR2 gene CNVs was investigated in six Chinese cattle breeds (XN, QC, NY, JA, LX and PN), and the results showed higher CNV polymorphisms in XN, QC and NY cattle. Next, association analysis between growth traits and SSTR2 CNV was performed for XN, QC and NY cattle. In NY, individuals with fewer copies showed better performance than those with more copies. Further, the effects of SSTR2 CNV on the SSTR2 mRNA level were also investigated, but revealed no significant correlation in either muscle or adipose tissue of adult NY cattle. The results suggested the potential for use of SSTR2 CNV as a marker for the molecular breeding of NY cattle.


Corresponding author

Author for correspondence: H. Chen, E-mail:


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Altshuler, DM, Gibbs, RA, Peltonen, L, Dermitzakis, E, Schaffner, SF, Yu, F, Bonnen, PE, de Bakker, PIW, Deloukas, P, Gabriel, SB, Gwilliam, R, Hunt, S, Inouye, M, Jia, X, Palotie, A, Parkin, M, Whittaker, P, Chang, K, Hawes, A, Lewis, LR, Ren, Y, Wheeler, D, Muzny, DM, Barnes, C, Darvishi, K, Hurles, M, Korn, JM, Kristiansson, K, Lee, C, McCarroll, SA, Nemesh, J, Keinan, A, Montgomery, SB, Pollack, S, Price, AL, Soranzo, N, Gonzaga-Jauregui, C, Anttila, V, Brodeur, W, Daly, MJ, Leslie, S, McVean, G, Moutsianas, L, Nguyen, H, Zhang, Q, Ghori, MJR, McGinnis, R, McLaren, W, Takeuchi, F, Grossman, SR, Shlyakhter, I, Hostetter, EB, Sabeti, PC, Adebamowo, CA, Foster, MW, Gordon, DR, Licinio, J, Manca, MC, Marshall, PA, Matsuda, I, Ngare, D, Wang, VO, Reddy, D, Rotimi, CN, Royal, CD, Sharp, RR, Zeng, C, Brooks, LD, McEwen, JE and Int HapMap, C (2010) Integrating common and rare genetic variation in diverse human populations. Nature 467, 5258.
Beckmann, JS, Estivill, X and Antonarakis, SE (2007) Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability. Nature Reviews Genetics 8, 639646.
Bennewitz, J, Reinsch, N, Guiard, V, Fritz, S, Thomsen, H, Looft, C, Kuhn, C, Schwerin, M, Weimann, C, Erhardt, G, Reinhardt, F, Reents, R, Boichard, D and Kalm, E (2004) Multiple quantitative trait loci mapping with cofactors and application of alternative variants of the false discovery rate in an enlarged granddaughter design. Genetics 168, 10191027.
Boichard, D, Grohs, C, Bourgeois, F, Cerqueira, F, Faugeras, R, Neau, A, Rupp, R, Amigues, Y, Boscher, MY and Leveziel, H (2003) Detection of genes influencing economic traits in three French dairy cattle breeds. Genetics Selection Evolution 35, 77101.
Buscail, L, Esteve, JP, Saint-Laurent, N, Bertrand, V, Reisine, T, O'Carroll, AM, Bell, GI, Schally, AV, Vaysse, N and Susini, C (1995) Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms. Proceedings of the National Academy of Sciences USA 92, 15801584.
Cao, XK, Huang, YZ, Ma, YL, Cheng, J, Qu, ZX, Ma, Y, Bai, YY, Tian, F, Lin, FP and Ma, YL (2018) Integrating CNVs into meta-QTL identified GBP4 as positional candidate for adult cattle stature. Functional & Integrative Genomics 18, 559567.
Chen, JS, Liang, QM, Li, HS, Yang, J, Wang, S and Long, JW (2009) Octreotide inhibits growth of colonic cancer SW480 cells by modulating the Wnt/β-catenin pathway. Pharmazie: An International Journal of Pharmaceutical Sciences 64, 126131.
Corbi-Botto, CM, Morales-Durand, H, Zappa, ME, Sadaba, SA, Peral-Garcia, P, Giovambattista, G and Diaz, S (2019) Genomic structural diversity in Criollo Argentino horses: analysis of copy number variations. Gene 695, 2631.
Di Gerlando, R, Sardina, MT, Tolone, M, Sutera, AM, Mastrangelo, S and Portolano, B (2019) Genome-wide detection of copy-number variations in local cattle breeds. Animal Production Science 59, 815822.
Doan, R, Cohen, N, Harrington, J, Veazey, K, Juras, R, Cothran, G, McCue, ME, Skow, L and Dindot, SV (2013) Identification of copy number variants in horses. Genome Research 22, 899907.
Fontanesi, L, Martelli, PL, Beretti, F, Riggio, V, Dall'Olio, S, Colombo, M, Casadio, R, Russo, V and Portolano, B (2010) An initial comparative map of copy number variations in the goat (Capra hircus) genome. Bmc Genomics 11, 639.
Gilbert, R, Bailey, D and Shannon, N (1993) Linear body measurements of cattle before and after 20 years of selection for postweaning gain when fed two different diets. Journal of Animal Science 71, 17121720.
Guryev, V, Saar, K, Adamovic, T, Verheul, M, Van Heesch, SAAC, Cook, S, Pravenec, M, Aitman, T, Jacob, H, Shull, JD, Hubner, N and Cuppen, E (2008) Distribution and functional impact of DNA copy number variation in the rat. Nature Genetics 40, 538545.
Henrichsen, CN, Chaignat, E and Reymond, A (2009) Copy number variants, diseases and gene expression. Human Molecular Genetics 18, R1R8.
Heron, I, Thomas, F, Dero, M, Gancel, A, Ruiz, J, Schatz, B and Kuhn, J (1993) Pharmacokinetics and efficacy of a long-acting formulation of the new somatostatin analog BIM 23014 in patients with acromegaly. The Journal of Clinical Endocrinology & Metabolism 76, 721727.
Hindson, BJ, Ness, KD, Masquelier, DA, Belgrader, P, Heredia, NJ, Makarewicz, AJ, Bright, IJ, Lucero, MY, Hiddessen, AL, Legler, TC, Kitano, TK, Hodel, MR, Petersen, JF, Wyatt, PW, Steenblock, ER, Shah, PH, Bousse, LJ, Troup, CB, Mellen, JC, Wittmann, DK, Erndt, NG, Cauley, TH, Koehler, RT, So, AP, Dube, S, Rose, KA, Montesclaros, L, Wang, S, Stumbo, DP, Hodges, SP, Romine, S, Milanovich, FP, White, HE, Regan, JF, Karlin-Neumann, GA, Hindson, CM, Saxonov, S and Colston, BW (2011) High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Analytical Chemistry 83, 86048610.
Hollox, EJ and Hoh, BP (2014) Human gene copy number variation and infectious disease. Human Genetics 133, 12171233.
Huang, H, Cao, J, Guo, G, Li, X, Wang, Y, Yu, Y, Zhang, S, Zhang, Q and Zhang, Y (2019) Genome-wide association study identifies QTLs for displacement of abomasum in Chinese Holstein cattle. Journal of Animal Science 97, 11331142.
Jiang, L, Jiang, J, Yang, J, Liu, X, Wang, J, Wang, H, Ding, X, Liu, J and Zhang, Q (2013) Genome-wide detection of copy number variations using high-density SNP genotyping platforms in Holsteins. BMC Genomics 14, article no. 131. doi:
Kader, A, Liu, X, Dong, K, Song, S, Pan, J, Yang, M, Chen, X, He, X, Jiang, L and Ma, Y (2016) Identification of copy number variations in three Chinese horse breeds using 70K single nucleotide polymorphism BeadChip array. Animal Genetics 47, 560569.
Karczewski, KJ and Snyder, MP (2018) Integrative omics for health and disease. Nature Reviews Genetics 19, 299310.
Karim, L, Takeda, H, Lin, L, Druet, T, Arias, JA, Baurain, D, Cambisano, N, Davis, SR, Farnir, F, Grisart, B, Harris, BL, Keehan, MD, Littlejohn, MD, Spelman, RJ, Georges, M and Coppieters, W (2011) Variants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature. Nature Genetics 43, 405413.
Karimi, K, Esmailizadeh, A, Wu, DD and Gondro, C (2018) Mapping of genome-wide copy number variations in the Iranian indigenous cattle using a dense SNP data set. Animal Production Science 58, 11921200.
Liu, M, Li, B, Huang, Y, Yang, M, Lan, X, Lei, C, Qu, W, Bai, Y and Chen, H (2016) Copy number variation of bovine MAPK10 modulates the transcriptional activity and affects growth traits. Livestock Science 194, 4450.
Liu, M, Zhou, Y, Rosen, BD, Van Tassell, CP, Stella, A, Tosser-Klopp, G, Rupp, R, Palhière, I, Colli, L, Sayre, B, Crepaldi, P, Fang, L, Mészáros, G, Chen, H and Liu, GE and the ADAPTmap Consortium (2018) Diversity of copy number variation in the worldwide goat population. Heredity 122, 636646.
MacDonald, JR, Ziman, R, Yuen, RKC, Feuk, L and Scherer, SW (2014) The database of genomic variants: a curated collection of structural variation in the human genome. Nucleic Acids Research 42, D986D992.
McCarroll, SA and Altshuler, DM (2007) Copy-number variation and association studies of human disease. Nature Genetics 39(suppl), S37-S42.
McClure, MC, Morsci, NS, Schnabel, RD, Kim, JW, Yao, P, Rolf, MM, McKay, SD, Gregg, SJ, Chapple, RH, Northcutt, SL and Taylor, JF (2010) A genome scan for quantitative trait loci influencing carcass, post-natal growth and reproductive traits in commercial Angus cattle. Animal Genetics 41, 597607.
Mills, RE, Walter, K, Stewart, C, Handsaker, RE, Chen, K, Alkan, C, Abyzov, A, Yoon, SC, Ye, K, Cheetham, RK, Chinwalla, A, Conrad, DF, Fu, Y, Grubert, F, Hajirasouliha, I, Hormozdiari, F, Iakoucheva, LM, Iqbal, Z, Kang, S, Kidd, JM, Konkel, MK, Korn, J, Khurana, E, Kural, D, Lam, HYK, Leng, J, Li, R, Li, Y, Lin, CY, Luo, R, Mu, XJ, Nemesh, J, Peckham, HE, Rausch, T, Scally, A, Shi, X, Stromberg, MP, Stuetz, AM, Urban, AE, Walker, JA, Wu, J, Zhang, Y, Zhang, ZD, Batzer, MA, Ding, L, Marth, GT, McVean, G, Sebat, J, Snyder, M, Wang, J, Ye, K, Eichler, EE, Gerstein, MB, Hurles, ME, Lee, C, McCarroll, SA and Korbel, JO and 1000 Genomes Project (2011) Mapping copy number variation by population-scale genome sequencing. Nature 470, 5965.
Moemke, S, Scholz, H, Doll, K, Rehage, J and Distl, O (2008) Mapping quantitative trait loci for left-sided displacement of the abomasum in German Holstein dairy cows. Journal of Dairy Science 91, 43834392.
Olias, P, Adam, I, Meyer, A, Scharff, C and Gruber, AD (2014) Reference genes for quantitative gene expression studies in multiple avian species. PLoS ONE 9, article no. e99678. doi: 10.1371/journal.pone.0099678
Pang, AW, MacDonald, JR, Pinto, D, Wei, J, Rafiq, MA, Conrad, DF, Park, H, Hurles, ME, Lee, C, Venter, JC, Kirkness, EF, Levy, S, Feuk, L and Scherer, SW (2010) Towards a comprehensive structural variation map of an individual human genome. Genome Biology 11, article no. R52. doi:
Rauch, F, Lalic, L, Roughley, P and Glorieux, FH (2010) Relationship between genotype and skeletal phenotype in children and adolescents with osteogenesis imperfecta. Journal of Bone and Mineral Research 25, 13671374.
Ritchie, MD, Holzinger, ER, Li, R, Pendergrass, SA and Kim, D (2015) Methods of integrating data to uncover genotype–phenotype interactions. Nature Reviews Genetics 16, 8597.
Sambrook, J, Russell, D and Russell, D (2001) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press.
Sebat, J, Lakshmi, B, Troge, J, Alexander, J, Young, J, Lundin, P, Maner, S, Massa, H, Walker, M, Chi, MY, Navin, N, Lucito, R, Healy, J, Hicks, J, Ye, K, Reiner, A, Gilliam, TC, Trask, B, Patterson, N, Zetterberg, A and Wigler, M (2004) Large-scale copy number polymorphism in the human genome. Science 305, 525528.
Shi, T, Xu, Y, Yang, M, Huang, Y, Lan, X, Lei, C, Qi, X, Yang, X and Chen, H (2016) Copy number variations at LEPR gene locus associated with gene expression and phenotypic traits in Chinese cattle. Animal Science Journal 87, 336343.
Wang, X, Nahashon, S, Feaster, TK, Bohannon-Stewart, A and Adefope, N (2010) An initial map of chromosomal segmental copy number variations in the chicken. BMC Genomics 11, article no. 351. doi:
Wang, J, Wang, H, Jiang, J, Kang, H, Feng, X, Zhang, Q and Liu, JF (2013 a) Identification of genome-wide copy number variations among diverse pig breeds using SNP genotyping arrays. PLoS ONE 8, article no. e68683. doi: 10.1371/journal.pone.0068683
Wang, S, Bao, Z, Liang, QM, Long, JW, Xiao, ZS, Jiang, ZJ, Liu, B, Yang, J and Long, ZX (2013 b) Octreotide stimulates somatostatin receptor-induced apoptosis of SW480 colon cancer cells by activation of glycogen synthase kinase-3β, A Wnt/β-catenin pathway modulator. Hepato-gastroenterology 60, 16391646.
Wang, J, Jiang, J, Wang, H, Kang, H, Zhang, Q and Liu, JF (2014) Enhancing genome-wide copy number variation identification by high density array CGH using diverse resources of pig breeds. PLoS ONE 9, article no. e87571. doi: 10.1371/journal.pone.0087571
Xu, Y, Zhang, L, Shi, T, Zhou, Y, Cai, H, Lan, X, Zhang, C, Lei, C and Chen, H (2013) Copy number variations of MICAL-L2 shaping gene expression contribute to different phenotypes of cattle. Mammalian Genome 24, 508516.
Xu, Y, Jiang, Y, Shi, T, Cai, H, Lan, X, Zhao, X, Plath, M and Chen, H (2017) Whole-genome sequencing reveals mutational landscape underlying phenotypic differences between two widespread Chinese cattle breeds. PLoS ONE 12, article no. e0183921. doi: 10.1371/journal.pone.0183921
Yalcin, B, Wong, K, Agam, A, Goodson, M, Keane, TM, Gan, X, Nellaker, C, Goodstadt, L, Nicod, J, Bhomra, A, Hernandez-Pliego, P, Whitley, H, Cleak, J, Dutton, R, Janowitz, D, Mott, R, Adams, DJ and Flint, J (2011) Sequence-based characterization of structural variation in the mouse genome. Nature 477, 326329.
Yamada, Y, Post, SR, Wang, K, Tager, HS, Bell, GI and Seino, S (1992 a) Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. Proceedings of the National Academy of Sciences USA 89, 251255.
Yamada, Y, Reisine, T, Law, SF, Ihara, Y, Kubota, A, Kagimoto, S, Seino, M, Seino, Y, Bell, GI and Seino, S (1992 b) Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase. Molecular Endocrinology 6, 21362142.
Yamada, Y, Kagimoto, S, Kubota, A, Yasuda, K, Masuda, K, Someya, Y, Ihara, Y, Li, Q, Imura, H, Seino, S and Y, S (1993) Cloning, functional expression and pharmacological characterization of a fourth (hSSTR4) and a fifth (hSSTR5) human somatostatin receptor subtype. Biochemical and Biophysical Research Communications 195, 844852.
Yang, L, Xu, L, Zhu, B, Niu, H, Zhang, W, Miao, J, Shi, X, Zhang, M, Chen, Y, Zhang, L, Gao, X, Gao, H, Li, L, Liu, GE and Li, J (2017 a) Genome-wide analysis reveals differential selection involved with copy number variation in diverse Chinese cattle. Scientific Reports 7, article no. 14299. doi:
Yang, M, Lv, J, Zhang, L, Li, M, Zhou, Y, Lan, X, Lei, C and Chen, H (2017 b) Association study and expression analysis of CYP4A11 gene copy number variation in Chinese cattle. Scientific Reports 7, article no. 46599. doi: 10.1038/srep46599
Zhang, F, Gu, W, Hurles, ME and Lupski, JR (2009) Copy number variation in human health, disease, and evolution. Annual Review of Genomics and Human Genetics 10, 451481.
Zhang, L, Jia, S, Yang, M, Xu, Y, Li, C, Sun, J, Huang, Y, Lan, X, Lei, C, Zhou, Y, Zhang, C, Zhao, X and Chen, H (2014) Detection of copy number variations and their effects in Chinese bulls. BMC Genomics 15, article no. 480. doi:
Zhang, RQ, Wang, JJ, Zhang, T, Zhai, HL and Shen, W (2019) Copy-number variation in goat genome sequence: a comparative analysis of the different litter size trait groups. Gene 696, 4046.
Zheng, X, Kuang, Y, Lv, W, Cao, D, Sun, Z, Jin, W and Sun, X (2017) Quantitative trait loci for morphometric traits in multiple families of common carp (Cyprinus carpio). Science China Life Sciences 60, 287297.


Association analysis of SSTR2 copy number variation with cattle stature and its expression analysis in Chinese beef cattle

  • J. Cheng (a1), R. Jiang (a1), X. K. Cao (a1), M. Liu (a1), Y. Z. Huang (a1), X. Y. Lan (a1), H. Cao (a2), C. Z. Lei (a1) and H. Chen (a1)...


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