中国农业科学Issue(14)：2872-2880,9.DOI:10.3864/j.issn.0578-1752.2014.14.017
全基因组关联分析鉴别白色杜洛克×二花脸F2资源家系中猪阴囊疝易感基因位点的鉴定
Genome-Wide Association Study Reveals Candidate Susceptibility Loci for Pig Scrotal Hernia Using Both F2 Intercross and Outbred Populations
摘要
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-WeinbergP≤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 nearbyIQGAP2,CHMP4B,SERINC3,ZNF334genes, 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.IQGAP2and 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.关键词
猪/全基因组关联分析/传递不平衡分析/阴囊疝/易感基因Key words
pig/genome-wide association study/transmission disequilibrium test/scrotal hernia/susceptibility gene引用本文复制引用
宿英,肖石军,任军,黄路生,丁能水,阮国荣,龙毅,杨斌,张志燕,邓玮芸,吴丽花,吕显山,艾华水..全基因组关联分析鉴别白色杜洛克×二花脸F2资源家系中猪阴囊疝易感基因位点的鉴定[J].中国农业科学,2014,(14):2872-2880,9.基金项目
国家自然科学基金（31071089）、教育部新世纪优秀人才计划（教技函[2012]80）、国家科技支撑计划（2011BAD28B01）、江西省青年科学家培养计划、福建省教育厅科技项目 （）
