Scientia Agricultura Sinica ›› 2014, Vol. 47 ›› Issue (14): 2872-2880.doi: 10.3864/j.issn.0578-1752.2014.14.017

• ANIMAL SCIENCE·VETERINARY SCIENCERE·SOURCE INSECT • Previous Articles     Next Articles

Genome-Wide Association Study Reveals Candidate Susceptibility Loci for Pig Scrotal Hernia Using Both F2 Intercross and Outbred Populations

 SU  Ying-1, RUAN  Guo-Rong-2, LONG  Yi-1, YANG  Bin-1, ZHANG  Zhi-Yan-1, DENG  Wei-Yun-1, WU  Li-Hua-1, 吕Xian-Shan-1 , AI  Hua-Shui-1, XIAO  Shi-Jun-1, REN  Jun-1, HUANG  Lu-Sheng-1, DING  Neng-Shui-1   

  1. 1、Candidate of National Key Laboratory for Animal Biotechnology, Jiangxi Agricultural University, Nanchang 330045;
    2、Fujian Vocational College of Agriculture, Fuzhou 350119
  • Received:2013-12-03 Online:2014-07-15 Published:2014-05-07

RichHTML

3

PDF

997

Abstract: 【Objective】Isolation of susceptible loci and positional candidate genes associated with pig scrotal hernia through case-control genome-wide association study (GWAS) based on haplotypes in a F2 White Duroc × Erhualian intercross and it’s replication in outbred trio families.【Method】Phenotypic data and Illumina porcine 60K SNP genotypes were collected from 1020 individuals in the White Duroc × Erhualian intercross (containing 19 affected pigs) and outbred trio families (containing 237 scrotal hernia pigs). Quality control was carried out using PLINK v1.07 for each population， separately. Samples of low (<90%) call rate were removed. SNP markers were removed if they had genotype-missing rates ＞0.1, or Hardy-Weinberg P≤10-3(based on Chi-squared test) or minor allele frequencies (MAF) ＜0.05, and SNPs on sex chromosomes or with unknown positions were also excluded. PHASEBOOK package was used to infer haplotypes from the genotyped individuals and to assign them to K ancestral haplotype clusters by hidden monto carlo markov models. The software GLASCOW based on generalized linear mixed models was used to carry out GWAS for pig scrotal hernia in the F2 intercross by the ancestral haplotype and significant SNPs were chosen to perform transmission disequilibrium test (TDT) based on both single SNP markers and haplotypes in the outbred population (containing 237 affected pigs) by Haploview. 【Result】After quality control, all samples in F2 population and 724 samples in outbred populations passed the filter and a final set of 38 033 SNPs and 96 SNPs were selected for GWAS and TDT analysis. In total, 108 SNPs with Bonferroni chromosome-wise significance (P＜2.63×10-5) were identified to be associated with scrotal hernia in F2 intercross, and located on SSC2, SSC8 and SSC17, respectively. The most promising SNP was located on SSC17. Five significant SNPs, located in on nearby IQGAP2，CHMP4B，SERINC3，ZNF334 genes, were replicated (located on SSC2 and SSC17) in outbred trio families by TDT analysis. TDT analysis based on haplotype revealed that two haplotypes contribute to risk of scrotal hernia, one of which was overlapped with two significant SNP on SSC17 in the TDT analysis based on single marker. IQGAP2 and CHMP4B genes close to the SNPs most associated with pig scrotal hernia were selected as positional candidate genes according to its biological and physiological functions.【Conclusion】A GWAS with small samples was conducted and variation and replication test was performed in a larger populations, which revealed 5 susceptible loci for pig scrotal hernia both in the F2 intercross and the outbred populations. IQGAP2 and CHMP4B may play a role in the risk of scrotal hernia, and deeper analysis should be carried out in the future study.

Key words: pig , genome-wide association study , transmission disequilibrium test , scrotal hernia , susceptibility gene

[1]Walters J R. Have we forgotten about inherited disease//AGBU Pig Genetics Workshop, 2010: 27-28.

[2]孙淑东, 殷凤振, 刘文明, 来长海. 仔猪腹股沟阴囊疝的预防及治疗措施. 山东畜牧兽医, 2011, 32(8): 30-31.

Sun S D, Yin F Z, Liu W M, Lai C H. Piglets scrotal/inguinal hernia prevention and treatment measures. Shandong Journal of Animal Husbandry and Veterinary Science, 2011, 32 (8): 30-31. (in Chinese)

[3]Chang K S, Chang J H. Animal models of pediatric surgical diseases. Pediatric Surgery International 1994, 9(5/6): 307-322.

[4]Gatphayak K, Chongkasikit N, Charoensook R, Laenoi W, Vearasilp T, Sardsud V, Knorr C, ter Meulen U, Brenig B. Present situation of porcine hernia inguinalis/scrotalis in Thailand. The Global Food & Product Chain-Dynamics, Innovalions, Conficts, Strategies, Tropentag Dctober 11-13, 2005.

[5]Grindflek E, Moe M, Taubert H, Simianer H, Lien S, Moen T. Genome-wide linkage analysis of inguinal hernia in pigs using affected sib pairs. BMC Genetics, 2006, 7(1): 25.

[6]Ding N S, Mao H R, Guo Y M, Ren J, Xiao S J, Wu G Z, Shen H Q, Wu L H, Ruan G F, Brenig B. A genome-wide scan reveals candidate susceptibility loci for pig hernias in an intercross between White Duroc and Erhualian. Journal of Animal Science, 2009, 87(8): 2469-2474.

[7]Du F X, Mathialagan N, Dyer C, Grosz M, Messer L, Clutter A, Wang T, Lohuis M, Byatt J. Mapping genes affecting scrotal hernia condition in domestic pigs. Journal of Dairy Science, 2004, 87: 453-453.

[8]Du Z Q, Zhao X, Vukasinovic N, Rodriguez F, Clutter AC, Rothschild M F. Association and haplotype analyses of positional candidate genes in five genomic regions linked to scrotal hernia in commercial pig lines. PloS One, 2009, 4(3): e4837.

[9]Tanyel F, Müftüoglu S, Dagdeviren A, Kaymaz F, Büyükpamukçu N. Myofibroblasts defined by electron microscopy suggest the dedifferentiation of smooth muscle within the sac walls associated with congenital inguinal hernia. BJU International, 2001, 87(3): 251-255.

[10]Tanyel F C, Erdem S, Büyükpamukçu N, Tan E. Smooth muscle within incomplete obliterations of processus vaginalis lacks apoptotic nuclei. Urologia Internationalis, 2002, 69(1): 42-45.

[11]Rodrigues Junior A J, Rodrigues C J, Cunha A C, Jin Y. Quantitative analysis of collagen and elastic fibers in the transversalis fascia in direct and indirect inguinal hernia. Revista do Hospital das Clínicas, 2002, 57(6): 265-270.

[12]Rodrigues C J, Yoo J H, Rodrigues Junior A J. Elastin (ELN) gene point mutation in patients with inguinal hernia. Genetics and Molecular Biology, 2006, 29(1): 45-46.

[13]Andersson L, Georges M. Domestic-animal genomics: deciphering the genetics of complex traits. Nature Reviews Genetics, 2004, 5(3): 202-212.

[14]兰旅涛, 郭源梅, 陈从英, 杨斌, 毛辉荣, 任军, 周利华. 在白色杜洛克× 二花脸 F2 资源家系中定位影响猪 210 日龄 8 个体尺性状的 QTL. 中国农业科学, 2010, 43(15): 3214-3220.

Lan L T, Guo Y M, Chen C Y, Yang B, Mao H R, Ren J, Zhou L H. QTL Mapping for eight traits related to porcine body dimensions at 210 days in a White Duroc × Erhualian F2 resource population. Scientia Agricultura Sinica, 2010, 43(15): 3214-3220. (in Chinese)

[15]Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira M A, Bender D, Maller J, Sklar P, De Bakker P I, Daly M J. PLINK: a tool set for whole-genome association and population-based linkage analyses. The American Journal of Human Genetics, 2007, 81(3): 559-575.

[16]Druet T, Georges M. A hidden Markov model combining linkage and linkage disequilibrium information for haplotype reconstruction and quantitative trait locus fine mapping. Genetics, 2010, 184(3): 789-798.

[17]Zhang Z, Guillaume F, Sartelet A, Charlier C, Georges M, Farnir F, Druet T. Ancestral haplotype-based association mapping with generalized linear mixed models accounting for stratification. Bioinformatics, 2012, 28(19): 2467-2473.

[18]Yang Q, Cui J, Chazaro I, Cupples L A, Demissie S. Power and type I error rate of false discovery rate approaches in genome-wide association studies. BMC Genetics, 2005, 6(Suppl 1): 134.

[19]Barrett J C, Fry B, Maller J, Daly M. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21(2): 263-265.

[20]Horvath S, Xu X, Laird N M. The family based association test method: strategies for studying general genotype–phenotype associations. European Journal of Human Genetics, 2001, 9(4): 301-306.

[21]Klein R J, Zeiss C, Chew E Y, Tsai J Y, Sackler R S, Haynes C, Henning A K, SanGiovanni J P, Mane S M, Mayne S T. Complement factor H polymorphism in age-related macular degeneration. Science, 2005, 308(5720): 385-389.

[22]McCarthy M I, Hirschhorn J N. Genome-wide association studies: potential next steps on a genetic journey. Human Molecular Genetics, 2008, 17(R2): R156-R165.

[23]Brown M D, Sacks D B. IQGAP1 in cellular signaling: bridging the GAP. Trends in Cell Biology, 2006, 16(5): 242-249.

[24]Katoh K, Shibata H, Suzuki H, Nara A, Ishidoh K, Kominami E, Yoshimori T, Maki M. The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. Journal of Biological Chemistry, 2003, 278(40): 39104-39113.

[25]Vito P, Pellegrini L, Guiet C, D’Adamio L. Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction. Journal of Biological Chemistry, 1999, 274(3): 1533-1540.

[26]Mahul-Mellier A-L, Hemming F J, Blot B, Fraboulet S, Sadoul R. Alix, making a link between apoptosis-linked gene-2, the endosomal sorting complexes required for transport, and neuronal death in vivo. The Journal of Neuroscience, 2006, 26(2): 542-549.

[27]Avila M, Kirchhoff M, Marle N, Hove H D, Chouchane M, Thauvin‐Robinet C, Masurel A, Mosca‐Boidron A L, Callier P, Mugneret F. Delineation of a new chromosome 20q11. 2 duplication syndrome including the ASXL1 gene. American Journal of Medical Genetics Part A, 2013, 161(7): 1594-1598.

[28]Li X, Leo BM, Beck G, Balian G, Anderson G D. Collagen and proteoglycan abnormalities in the GDF-5-deficient mice and molecular changes when treating disk cells with recombinant growth factor. Spine, 2004, 29(20): 2229-2234.
[1] TAN XianMing,ZHANG JiaWei,WANG ZhongLin,CHEN JunXu,YANG Feng,YANG WenYu. Prediction of Maize Yield in Relay Strip Intercropping Under Different Water and Nitrogen Conditions Based on PLS [J]. Scientia Agricultura Sinica, 2022, 55(6): 1127-1138.
[2] CHEN XueSen, YIN HuaLin, WANG Nan, ZHANG Min, JIANG ShengHui, XU Juan, MAO ZhiQuan, ZHANG ZongYing, WANG ZhiGang, JIANG ZhaoTao, XU YueHua, LI JianMing. Interpretation of the Case of Bud Sports Selection to Promote the High-Quality and Efficient Development of the World’s Apple and Citrus Industry [J]. Scientia Agricultura Sinica, 2022, 55(4): 755-768.
[3] BaoHua CHU,FuGuo CAO,NingNing BIAN,Qian QIAN,ZhongXing LI,XueWei LI,ZeYuan LIU,FengWang MA,QingMei GUAN. Resistant Evaluation of 84 Apple Cultivars to Alternaria alternata f. sp. mali and Genome-Wide Association Analysis [J]. Scientia Agricultura Sinica, 2022, 55(18): 3613-3628.
[4] MingJie XING,XianHong GU,XiaoHong WANG,Yue HAO. Effects of IL-15 Overexpression on Myoblast Differentiation of Porcine Skeletal Muscle Cells [J]. Scientia Agricultura Sinica, 2022, 55(18): 3652-3663.
[5] YANG ChangPei,WANG NaiXiu,WANG Kai,HUANG ZiQing,LIN HaiLan,ZHANG Li,ZHANG Chen,FENG LuQiu,GAN Ling. Effects and Mechanisms of Exogenous GABA Against Oxidative Stress in Piglets [J]. Scientia Agricultura Sinica, 2022, 55(17): 3437-3449.
[6] CHANG LiGuo,HE KunHui,LIU JianChao. Mining of Genetic Locus of Maize Stay-Green Related Traits Under Multi-Environments [J]. Scientia Agricultura Sinica, 2022, 55(16): 3071-3081.
[7] DENG FuLi,SHEN Dan,ZHONG RuQing,ZHANG ShunFen,LI Tao,SUN ShuDong,CHEN Liang,ZHANG HongFu. Non-Starch Polysaccharide Enzymes Cocktail of Corn-Miscellaneous Meal-Based Diet Optimization by In Vitro Method and Its Effects on Intestinal Microbiome in Finishing Pigs [J]. Scientia Agricultura Sinica, 2022, 55(16): 3242-3255.
[8] JIN MengJiao,LIU Bo,WANG KangKang,ZHANG GuangZhong,QIAN WanQiang,WAN FangHao. Light Energy Utilization and Response of Chlorophyll Synthesis Under Different Light Intensities in Mikania micrantha [J]. Scientia Agricultura Sinica, 2022, 55(12): 2347-2359.
[9] HU RongRong,DING ShiJie,GUO Yun,ZHU HaoZhe,CHEN YiChun,LIU Zheng,DING Xi,TANG ChangBo,ZHOU GuangHong. Effects of Trolox on Proliferation and Differentiation of Pig Muscle Stem Cells [J]. Scientia Agricultura Sinica, 2021, 54(24): 5290-5301.
[10] TANG ZhenShuang,YIN Dong,YIN LiLin,MA YunLong,XIANG Tao,ZHU MengJin,YU Mei,LIU XiaoLei,LI XinYun,QIU XiaoTian,ZHAO ShuHong. To Evaluate the “Two-Step” Genomic Selection Strategy in Pig by Simulation [J]. Scientia Agricultura Sinica, 2021, 54(21): 4677-4684.
[11] ZHANG DanDan,XU TengTeng,GAO Di,QI Xin,NING Wei,RU ZhenYuan,ZHANG XiangDong,GUO TengLong,SHENTU LuYan,YU Tong,MA YangYang,LI YunSheng,ZHANG YunHai,CAO ZuBing. Transcription Factor TEAD4 Regulates Early Embryonic Development in Pigs [J]. Scientia Agricultura Sinica, 2021, 54(20): 4456-4465.
[12] SHI Jiang,WANG JiaTong,PENG QunHua,LÜ Haipeng,BALDERMANN Susanne,LIN Zhi. Changes in Lipid-Soluble Pigments in Fresh Tea Leaves Treated by Methyl Jasmonate and During Postharvest Oolong Tea Manufacturing [J]. Scientia Agricultura Sinica, 2021, 54(18): 3984-3997.
[13] DU Xing,ZENG Qiang,LIU Lu,LI QiQi,YANG Liu,PAN ZengXiang,LI QiFa. Identification of the Core Promoter of Linc-NORFA and Its Transcriptional Regulation in Erhualian Pig [J]. Scientia Agricultura Sinica, 2021, 54(15): 3331-3342.
[14] YU ZhengWang,ZHOU ZhongXin. Functions of Antibacterial and Inducing Defense Peptide Expression of Medium-Chain Fatty Acid and Its Application in Piglet Feeds [J]. Scientia Agricultura Sinica, 2021, 54(13): 2895-2905.
[15] WANG JiQing,REN Yi,SHI XiaoLei,WANG LiLi,ZHANG XinZhong,SULITAN· GuZhaLiAYi,XIE Lei,GENG HongWei. Genome-Wide Association Analysis of Superoxide Dismutase (SOD) Activity in Wheat Grain [J]. Scientia Agricultura Sinica, 2021, 54(11): 2249-2260.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
京ICP备09089781号-30
Copyright 2018 © Editorial office of Scientia Agricultura Sinica
Tel: 86-010-82106279    E-mail: zgnykx@mail.caas.net.cn
Supported by Beijing Magtech Co.Ltd