Selective sweep is used to detect genomic regions with reduced variation in allele frequency in any population experiencing divergent selection for specific traits. Here, we determined the feasibility of the selective sweep approach for finding genes important for AF deposition in chickens. The long-range haplotype test was employed, which detects selection signature by measuring the characteristics of haplotypes within the lean and fat lines divergently selected for AF content. There were 5357 and 5593 core regions in the lean and fat lines, respectively. When comparing the average marker spacing with mean core length and number of SNPs forming cores, we revealed that core regions are more likely to appear in regions with higher marker density.
The selection signatures on the whole genome were calculated, and a subset of putative core regions with significant REHH P-values (P<0.01) was identified. The genes in these core regions were detected and 10 genes, including RB1, BBS7, MAOA, MAOB, EHBP1, LRP2BP, LRP1B, MYO7A, MYO9A and PRPSAP1, were important for fatness. Among these 10 important genes, seven genes, including RB1, BBS7, MAOA, MAOB, EHBP1, LRP2BP and LRP1B, were all in the QTL regions reported previously for AF in chickens (Table 5). Although the other three genes, including MYO7A, MYO9A and PRPSAP1, were not in the QTL regions, these genes were also important for the AF deposition.
The known functions of these 10 genes were analyzed and the results indicated that they were likely to be linked with fatness. The RB1 gene regulates the C/EBP-DNA-binding activity during 3T3-L1 adipogenesis and plays a key role in adipocyte differentiation [40, 41].
The BBS7 gene is a member of the Bardet-Biedl syndrome (BBS) family. BBS is a pleiotropic genetic disorder characterized by obesity, photoreceptor degeneration, polydactyly, hypogenitalism, renal abnormalities, and developmental delay . BBS is recognized to be a genetically heterogeneous autosomal recessive disorder mapped to eight loci . Positional cloning and candidate genes identified six BBS genes, including BBS1, BBS2, BBS4, BBS6, BBS7, and BBS8. These BBS genes may be important for obesity.
The MAOA and MAOB are two enzymes important for dopamine production. The dopamine levels influence the risk of obesity and MAOA and MOAB may be implicated in human obesity .
The EHBP1 gene is required for insulin-stimulated GLUT4 movements . Insulin stimulates glucose transport in adipose tissues by recruiting intracellular membrane vesicles containing the glucose transporter GLUT4 to the plasma membrane . The mechanisms involved in the biogenesis of these vesicles and their translocation to the cell surface were studied and the results indicated that EHD1 and EHBP1 are required for perinuclear localization of GLUT4, and the loss of EHBP1 disrupts insulin-regulated GLUT4 recycling in cultured adipocytes . This indicates that the EHBP1 gene may be important in adipocyte differentiation.
The LRP2BP and LRP1B genes are two members of the low-density lipoprotein receptor family that participates in a wide range of physiological processes, including the regulation of lipid metabolism, protection against atherosclerosis, neurodevelopment, and transport of nutrients and vitamins .
The MYO7A and MYO9A are two myosin genes. A spontaneous mutant mouse line, Myo7ash1-6J, was used to study the function of the MYO7A gene, and the result indicated that the mutant male homozygous mice displayed decreased body weight and body fat . The MYO9A gene was in the BBS4 region of chromosome 15q22-q23 , which might be important for obesity.
The PRPSAP1 gene is named as phosphoribosyl pyrophosphate synthetase-associated protein 1. The results of differentially expressed genes associated with insulin resistance indicate that PRPSAP1 gene is associated with percentage of body fat .
The associations of these 10 genes with obesity or lipid metabolism were mainly in humans and mice. Because of the high conservation of these genes between humans, mice and chickens, the 10 genes might also be important for AF deposition in chickens.