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 chr4:73206169-73208244 as a key region harboring functional variants affecting the growth of chickens.
Decreased expression of chicken cholecystokinin A receptor (CCKAR) attenuates satiety, which contributes to increased food intake and growth for modern broilers. The study aims to define the core promoter of CCKAR, and to identify variants associated with expression activity. A 21 kb region around the CCKAR was re-sequenced to detect sequence variants. A series of 5′-deleted promoter plasmids were constructed to define the core promoter of CCKAR. The effects of sequence variants located in promoter (PSNP) and conserved (CSNP) regions on promoter activity were analyzed by comparing luciferase activity between haplotypes. A total of 182 variants were found in the 21 kb region. There were no large structural variants around CCKAR. pNL−328/+183, the one with the shortest insertion, showed the highest activity among the six promoter constructs, implying that the key cis elements regulating CCKAR expression are mainly distributed 328 bp upstream. We detected significant activity differences between high- and low-growth associated haplotypes in four of the six promoter constructs. The high-growth haplotypes of constructs pNL−1646/+183, pNL−799/+183 and pNL−528/+183 showed lower activities than the low-growth haplotypes, which is consistent with decreased expression of CCKAR in high-growth chickens. Lower expression of the high-growth allele was also detected for the CSNP5-containing construct. The data suggest that the core promoter of CCKAR is located the 328 bp region upstream from the transcription start site. Lower expression activities shown by the high-growth haplotypes in the reporter assay suggest that CSNP5 and variants located between 328 bp and 1646 bp upstream form a promising molecular basis for decreased expression of CCKAR and increased growth in chickens.
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