Please wait a minute...
Journal of Integrative Agriculture  2020, Vol. 19 Issue (3): 793-799    DOI: 10.1016/S2095-3119(19)62773-5
Special Issue: 动物科学Animal Science
Animal Science · Veterinary Medicine Advanced Online Publication | Current Issue | Archive | Adv Search |
Genetic parameter estimation and genome-wide association study (GWAS) of red blood cell count at three stages in a Duroc×Erhualian pig population
NAN Jiu-hong1*, YIN Li-lin1*, TANG Zhen-shuang1, CHEN Jian-hai1, ZHANG Jie1, WANG Hai-yan1, 2, DU Xiao-yong1, 2, LIU Xiang-dong1, 3  
1 Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, P.R.China
2 Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P.R.China
3 Key Lab of Swine Healthy Breeding of Ministry of Agriculture and Rural Affairs, Guangxi Yangxiang Co., Ltd., Guigang 537100, P.R.China
Download:  PDF in ScienceDirect  
Export:  BibTeX | EndNote (RIS)      
Abstract  
Red blood cells play an essential role in the immune system.  Moreover, red blood cell count (RBC) is an important clinical indicator of various diseases, including anemia, type 2 diabetes and the metabolic syndrome.  Thus, it is necessary to reveal the genetic mechanism of RBC for animal disease resistance breeding.  However, quite a few studies had focused on porcine RBC, especially at different stages.  Thus, studies on porcine RBC at different stages are needed for disease resistant breeding.  In this study, the porcine RBC of 20-, 33-, and 80-day old were measured, and genetic parameter estimation and genome-wide association study (GWAS) were both performed.  As a result, the heritability was about 0.6 at the early stages, much higher than that at 80 days.  Nine novel genome wide significant single nucleotide polymorphisms (SNPs), located at Sus scrofa chromosome (SSC)3, 4, 8, 9, 10 and 15, respectively, were identified.  Further, TGFβ2, TMCC2 and PPP1R15B genes were identified as important candidate genes of porcine red blood cell count.  So different SNPs and candidate genes were found significantly associated with porcine RBC at different stages, suggesting that different genes might play key roles on porcine RBC at different stages.  Overall, new evidences were offered in this study for the genetic bases of animal RBC, and that the SNPs and candidate genes would be useful for disease resistant breeding of pig.
Keywords:  RBC        genome-wide association        SNP        candidate gene        pig  
Received: 19 October 2018   Accepted:
Fund: This work was supported by the National Natural Science Foundation of China (31572375, NSFC-CGIAR31361140365), the Fundamental Research Funds for the Central Universities of China (2662016PY006), the National High Technology Research and Development Program of China (2013AA102502), the earmarked fund for China Agriculture Research System (CARS-35), and the Dabeinong Group Promoted Project for Young Scholar of Huazhong Agricultural University, China (2017DBN019).
Corresponding Authors:  Correspondence LIU Xiang-dong, E-mail: liuxiangdong@mail.hzau.edu.cn; DU Xiao-yong, E-mail: duxiaoyong@mail.hzau.edu.cn   
About author:  * These authors contributed equally to this study.

Cite this article: 

NAN Jiu-hong, YIN Li-lin, TANG Zhen-shuang, CHEN Jian-hai, ZHANG Jie, WANG Hai-yan, DU Xiao-yong, LIU Xiang-dong . 2020. Genetic parameter estimation and genome-wide association study (GWAS) of red blood cell count at three stages in a Duroc×Erhualian pig population. Journal of Integrative Agriculture, 19(3): 793-799.

Abbott D, Wang K, Shapiro A, Trudy B, Di P, Di Jorge P. 2007. genome wide scan of complete blood count (CBC) measures suggests strong linkage of red blood cell (RBC) count to chromosome 4q25. Blood, 110, 11.
Arnold S J, Stappert J, Bauer A, Kispert A, Herrmann B G, Kemler R. 2000. Brachyury is a target gene of the Wnt/beta-catenin signaling pathway. Mechanisms of Development, 91, 249–258.
Dal Colletto G M, Fulker D W, Barretto O C, Kolya M. 1993. Genetic and environmental effects on blood cells. Acta Geneticae Medicae et Gemellologiae, 42, 245.
Flori L, Gao Y, Laloë D, Lemonnier G, Leplat J J, Teillaud A, Cossalter A M, Laffitte J, Pinton P, De V C. 2011. Immunity traits in pigs: Substantial genetic variation and limited covariation. PLoS ONE, 6, e22717.
Garner C, Tatu T, Reittie J E, Littlewood T, Darley J, Cervino S, Farrall M, Kelly P, Spector T D, Thein S L. 2000. Genetic influences on F cells and other hematologic variables: A twin heritability study. Blood, 95, 342–346.
Harding H P, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, Ron D. 2000. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Molecular Cell, 6, 1099–1108.
Harding H P, Zhang Y, Scheuner D, Chen J J, Kaufman R J, Ron D. 2009. Ppp1r15 gene knockout reveals an essential role for translation initiation factor 2 alpha (eIF2α) dephosphorylation in mammalian development. Proceedings of the National Academy of Sciences of the United States of America, 106, 1832–1837.
Hinckley J D, Abbott D, Burns T L, Heiman M, Shapiro A D, Wang K, Di P J. 2013. Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits. Molecular Genetics & Genomic Medicine, 1, 131–141.
Kloft N, Neukirch C, Von H G, Bobkiewicz W, Weis S, Boller K, Husmann M. 2012. A subunit of eukaryotic translation initiation factor 2α-phosphatase (CreP/PPP1R15B) regulates membrane traffic. Journal of Biological Chemistry, 287, 35299.
Lasley J F. 1978. Genetics of Livestock Improvement. Prentice-Hall, Inc., Upper Saddle River, New Jersey.
Liu X, Huang J, Yang S, Zhao Y, Xiang A, Cao J, Fan B, Wu Z, Zhao J, Zhao S. 2014. Whole blood transcriptome comparison of pigs with extreme production of in vivo dsRNA-induced serum IFN-a. Developmental & Comparative Immunology, 44, 35.
Liu X, Huang M, Fan B, Buckler E S, Zhang Z. 2016. Iterative usage of fixed and random effect models for powerful and efficient genome-wide association studies. PLoS Genetics, 12, e1005767.
Luo W, Chen S, Cheng D, Wang L, Li Y, Ma X, Song X, Liu X, Li W, Liang J. 2012. Genome-wide association study of porcine hematological parameters in a Large white×Minzhu F2 resource population. International Journal of Biological Sciences, 8, 870–881.
Madsen P, Jensen J. 2013. A user’s guide to DMU. Version 6, release 5.2. Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, Tjele, Denmark.
Majka M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K,  Pietrzkowski Z, Kowalska M A, Gewirtz A M, Emerson S G, Ratajczak M Z. 2001. Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood, 97, 3075–3085.
Miao Y, Soudy F, Zhong X, Liao M, Zhao S, Li X. 2017. Candidate gene identification of feed efficiency and coat color traits in a C57BL/6J×Kunming F2 mice population using genome-wide association study.  Biomed Research International, 2017, 1–7.
Mpetile Z, Young J M, Gabler N K, Dekkers J C M, Tuggle C K. 2015. Assessing peripheral blood cell profile of Yorkshire pigs divergently selected for residual feed intake. Journal of Animal Science, 93, 892–899.
Purcell S, Neale B M, Toddbrown K, Thomas L, Ferreira M A R, Bender D, Maller J B, Sklar P, De Bakker P I W, Daly M J. 2007. PLINK: A tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics, 81, 559–575.
Reiner G, Clemens N, Fischer R, Kohler F, Berge T, Hepp S, Willems H. 2009. Mapping of quantitative trait loci for clinicalchemical traits in swine. Animal Genetics, 40, 57–64.
Shau H, Gupta R K, Golub S H. 1993. Identification of a natural killer enhancing factor (NKEF) from human erythroid cells. Cellular Immunology, 147, 1–11.
Siegel I, Liu T L, Gleicher N. 1981a. Red cell immune adherence. Lancet, 318, 878–879.
Siegel I, Liu T L, Gleicher N. 1981b. The red-cell immune system. Lancet, 318, 556–559.
Simmons D. 2010. Increased red cell count in diabetes and pre-diabetes. Diabetes Research & Clinical Practice, 90, e50.
Thompson P D, Hannah T, Andy B, Harry N, Steve K, Jan N, May T. 2010. Claudin 13, a member of the claudin family regulated in mouse stress induced erythropoiesis. PLoS ONE, 5, e12667.
Vanraden P M. 2008. Efficient methods to compute genomic predictions. Journal of Dairy Science, 91, 4414–4423.
Wang J Y, Luo Y R, Fu W X, Lu X, Zhou J P, Ding X D, Liu J F, Zhang Q. 2013. Genome-wide association studies for hematological traits in swine. Animal Genetics, 44, 34–43.
Wang Z S, Song Z C, Bai J H, Fei L, Tao W, Ji Q, Jian H. 2013. Red blood cell count as an indicator of microvascular complications in Chinese patients with type 2 diabetes mellitus. Vascular Health & Risk Management, 2013, 237.
Yang Q, Kathiresan S, Lin J, Tofler G H, Odonnell C J. 2007. Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study. BMC Medical Genetics, 8, 1–11.
Yang S, Liu X, Li X, Sun S, Sun F, Fan B, Zhao S. 2013. MicroRNA-124 reduces caveolar density by targeting caveolin-1 in porcine kidney epithelial PK15 cells. Molecular & Cellular Biochemistry, 384, 213–219.
Zhang J, Chen J H, Liu X D, Wang H Y, Liu X L, Li X Y, Wu Z F, Zhu M J, Zhao S H. 2016. Genomewide association studies for hematological traits and T lymphocyte subpopulations in a Duroc×Erhualian F-2 resource population. Journal of Animal Science, 94, 5028–5041.
Zhang Z, Hong Y, Gao J, Xiao S, Ma J, Zhang W, Ren J, Huang L. 2013. Genome-wide association study reveals constant and specific loci for hematological traits at three time stages in a White Duroc×Erhualian F2 resource population. PLoS ONE, 8, e63665.
[1] Wei Liu, Xueling Huang, Meng Ju, Mudi Sun, Zhimin Du, Zhensheng Kang, Jie Zhao. Molecular evidence of the west-to-east dispersal of Puccinia striiformis f. sp. tritici in central Shaanxi and the migration of the inoculum from Gansu[J]. >Journal of Integrative Agriculture, 2025, 24(6): 2251-2265.
[2] Zipeng Zhang, Siyuan Xing, Ao Qiu, Ning Zhang, Wenwen Wang, Changsong Qian, Jia’nan Zhang, Chuduan Wang, Qin Zhang, Xiangdong Ding. The development of a porcine 50K SNP panel using genotyping by target sequencing and its application[J]. >Journal of Integrative Agriculture, 2025, 24(5): 1930-1943.
[3] Huairen Zhang, Tauseef Taj Kiani, Huabang Chen, Juan Liu, Xunji Chen. Genome wide association analysis reveals multiple QTLs controlling root development in maize [J]. >Journal of Integrative Agriculture, 2025, 24(5): 1656-1670.
[4] Yang Wang, Chunhua Mu, Xiangdong Li, Canxing Duan, Jianjun Wang, Xin Lu, Wangshu Li, Zhennan Xu, Shufeng Sun, Ao Zhang, Zhiqiang Zhou, Shenghui Wen, Zhuanfang Hao, Jienan Han, Jianzhou Qu, Wanli Du, Fenghai Li, Jianfeng Weng. A genome-wide association study and transcriptome analysis reveal the genetic basis for the Southern corn rust resistance in maize[J]. >Journal of Integrative Agriculture, 2025, 24(2): 453-466.
[5] Kaiyuan Ji, Yiwei Zhao, Xin Yuan, Chun’e Liang, Xueqing Zhang, Wenli Tian, Tong Yu, Yangyang Ma, Yinghui Ling, Yunhai Zhang. circKIF27 inhibits melanogenesis and proliferation by targeting miR-129-5p/TGIF2 pathway in goat melanocytes[J]. >Journal of Integrative Agriculture, 2025, 24(10): 3997-4011.
[6] Xiaogang He, Zirong Li, Sicheng Guo, Xingfei Zheng, Chunhai Liu, Zijie Liu, Yongxin Li, Zheming Yuan, Lanzhi Li. Epistasis-aware genome-wide association studies provide insights into the efficient breeding of high-yield and high-quality rice[J]. >Journal of Integrative Agriculture, 2024, 23(8): 2541-2556.
[7] Hongge Li, Shurong Tang, Zhen Peng, Guoyong Fu, Yinhua Jia, Shoujun Wei, Baojun Chen, Muhammad Shahid Iqbal, Shoupu He, Xiongming Du. Genetic dissection and origin of pleiotropic loci underlying multi-level fiber quality traits in upland cotton (Gossypium hirsutum L.)[J]. >Journal of Integrative Agriculture, 2024, 23(10): 3250-3263.
[8] Simin Liao, Zhibin Xu, Xiaoli Fan, Qiang Zhou, Xiaofeng Liu, Cheng Jiang, Liangen Chen, Dian Lin, Bo Feng, Tao Wang.

Genetic dissection and validation of a major QTL for grain weight on chromosome 3B in bread wheat (Triticum aestivum L.) [J]. >Journal of Integrative Agriculture, 2024, 23(1): 77-92.

[9] SHA Xiao-qian, GUAN Hong-hui, ZHOU Yu-qian, SU Er-hu, GUO Jian, LI Yong-xiang, ZHANG Deng-feng, LIU Xu-yang, HE Guan-hua, LI Yu, WANG Tian-yu, ZOU Hua-wen, LI Chun-hui. Genetic dissection of crown root traits and their relationships with aboveground agronomic traits in maize[J]. >Journal of Integrative Agriculture, 2023, 22(11): 3394-3407.
[10] ZHANG Hua, WU Hai-yan, TIAN Rui, KONG You-bin, CHU Jia-hao, XING Xin-zhu, DU Hui, JIN Yuan, LI Xi-huan, ZHANG Cai-ying. Genome-wide association and linkage mapping strategies reveal genetic loci and candidate genes of phosphorus utilization in soybean[J]. >Journal of Integrative Agriculture, 2022, 21(9): 2521-2537.
[11] WANG Peng-fei, WANG Ming, SHI Zhi-bin, SUN Zhen-zhao, WEI Li-li, LIU Zai-si, WANG Shi-da, HE Xi-jun, WANG Jing-fei. Development of a recombinant pB602L-based indirect ELISA assay for detecting antibodies against African swine fever virus in pigs[J]. >Journal of Integrative Agriculture, 2022, 21(3): 819-825.
[12] ZHANG Xu-huan, LIU Hao, MA Xu-hui, ZHOU Gu-yi, RUAN Hong-qiang, CUI Hong-wei, PANG Jun-ling, SIFFAT Ullah Khan, ZONG Na, WANG Ren-zhong, LENG Peng-fei, ZHAO Jun. Genome-wide association study and metabolic pathway prediction of barrenness in maize as a response to high planting density[J]. >Journal of Integrative Agriculture, 2022, 21(12): 3514-3523.
[13] JIA Jia, WANG Huan, CAI Zhan-dong, WEI Ru-qian, HUANG Jing-hua, XIA Qiu-ju, XIAO Xiao-hui, MA Qi-bin, NIAN Hai, CHENG Yan-bo. Identification and validation of stable and novel quantitative trait loci for pod shattering in soybean [Glycine max (L.) Merr.][J]. >Journal of Integrative Agriculture, 2022, 21(11): 3169-3184.
[14] YU Hai-xia, DUAN Xi-xian, SUN Ai-qing, SUN Xiao-xiao, ZHANG Jing-juan, SUN Hua-qing, SUN Yan-yan, NING Tang-yuan, TIAN Ji-chun, WANG Dong-xue, LI Hao, FAN Ke-xin, WANG Ai-ping, MA Wu-jun, CHEN Jian-sheng. Genetic dissection of the grain filling rate and related traits through linkage analysis and genome-wide association study in bread wheat[J]. >Journal of Integrative Agriculture, 2022, 21(10): 2805-2817.
[15] ZHANG Zhe, CHEN Zi-tao, DIAO Shu-qi, YE Shao-pan, WANG Jia-ying, GAO Ning, YUAN Xiao-long, CHEN Zan-mou, ZHANG Hao, LI Jia-qi. Identifying the complex genetic architecture of growth and fatness traits in a Duroc pig population[J]. >Journal of Integrative Agriculture, 2021, 20(6): 1607-1614.
No Suggested Reading articles found!