Abstract: 【Objective】 Genome-wide association study (GWAS) was used to demonstrate the molecular mechanism and genetic architecture of chicken spleen weight, which will provide a basis for improving hens health condition in late laying period. 【Method】 The resource population was from reciprocal by Dongxiang Blueshell Chicken and White Leghon, the spleen weight of 1 501 individuals from F2 generation was used as the experimental material. First, the F2 population genome DNA was genotyped by 600 K Affymetrix Axiom Chicken Genotyping Array. Then the quality control was conducted by APT software, some sporadic missing genotypes were imputed using BEAGLE procedure, principal component analysis was performed by PLINK software, genome-wide association study was carried out by GEMMA software, after these steps, the significant and suggestive loci association with spleen weight was identified. Besides, the heritability of spleen weight and chromosome was calculated by GCTA software. According to the false positive significant or suggestive loci, conditional analysis was carried out with the leading SNP as covariance and the linkage disequilibuium was analysis by Haploview. Eventually, the candidate genes were identified based on the gene annotation. 【Result】The phenotype of spleen weight showed extensive variations in late laying period. The heritability of spleen weight was 0.236. A total of 435 867 high quality SNPs were obtained after genotyped. The genomic inflation factor was 1.042 which showed that there is negligible inflation caused by population stratification. Totally, we found 412 and 281 SNPs for significant and suggestive association with spleen weight, respectively. The SNPs that located on GGA1 (gallus gallus chromosome 1), GGA4, GGA16 and GGA28, the significant region on GGA1 spanned from 161 to 174 Mb and ranged from 0.47 to 1.27 on GGA28, the suggestive significant SNPs located on 76 Mb on GGA4 and 175 kb on GGA16. Due to the linkage disequilibrium between the significant loci, the conditional analysis and linkage disequilibrium were performed. After conditional analysis of rs314001986 on GGA1 and rs312729296 on GGA28, the significant loci all dropped below threshold. The linkage disequilibrium analysis was performed by the significant loci on GGA4 and GGA16, the results showed that the suggestive loci showed strong linkage disequilibrium. The genes KCTD4, LDB2, HEP21, and PCASP2 that may involve in spleen growth development and immune response were considered as candidate gene after blasting against chicken genome reference assembly. Moreover, the heritability based on SNP of GGA1 was 9.25%, GGA28 was 4.55%. 【Conclusion】These results enriched the genetic architecture for spleen weight of adult hen in late laying period, the heritability of spleen weight was novel. By bioinformatics analysis the QTL detected for spleen weight was also novel, and 4 candidate genes identified.

Key words: chicken, spleen, genome-wide association study, resource population