Research Note: Fine mapping of sequence variants associated with body weight of Lueyang black-boned chicken in the CCKAR gene

Cholecystokinin A receptor (CCKAR) is a key receptor mediating satiety. Previous studies found that decreased expression of CCKAR attenuated satiety, and thus contributed to the high-growth of broiler chickens. The objective of this study is to map sequence variants associated with the growth of chickens in the CCKAR. The CCKAR and upstream 1.4 kb genomic sequences were resequenced to find out all sequence variants using 35 Lueyang black-boned chickens (LBC). Haplotypes were reconstructed using the PHASE program. Linkage disequilibrium between variants was analyzed using the Haploview software. Associations of 33 tag SNPs that captured 89% of all variants with body weight of LBC (n = 675) at 16 (BW16), 20 (BW20) weeks of age and the onset (BWOEP) of egg production were tested using linear mixed models. A total of 126 SNPs were found and formed 41 haplotypes in 35 resequenced samples. Average length of haplotype blocks is 129 bp, indicating that LBC maintains low linkage disequilibrium at the CCKAR locus. Eleven of 33 tag SNPs were significantly associated with BW16, but not with BW20 and BWOEP. These significantly associated variants were most (8/11) distributed in a 2 kb region (chr4:73206169-73208244) around the Exon3. They together with 33 captured variants potentially disrupted binding sites of 471 transcription factors. Twelve variants can disrupt appetite (FOXO1) or lipid metabolism-related TF (AR and C/ EBP) motifs. This study recognized chr4:7320616973208244 as a key region harboring functional variants affecting the growth of chickens.