Fine mapping of candidate regions associated with fat deposition in thin and fat tail sheep breeds suggests new insights into molecular aspects of fat tail selection
Abstract Background Fatness related traits are economically very important in sheep production and are associated with serious diseases in humans. The fat tail is a phenotype that divides domesticated sheep into two major groups. The objective of the present study is to refine the map location of candidate regions associated with fat deposition, obtained via two separate whole genome scans contrasting thin and fat tail breeds, and to determine the nature of the selection occurring in these regions using hitchhiking approach. Results Zel (thin tail) and Lori-Bakhtiari (fat tail) breed samples that had previously been run on the Illumina Ovine 50k BeadChip, were genotyped with a denser set of SNPs in the three candidate regions using a Sequenom Mass ARRAY platform. Statistical tests were then performed using different and complementary methods based on either site frequency (FST and Median homozygosity) or haplotype (iHS and XP-EHH). Results from candidate regions on chromosome 5 and X revealed clear evidence of selection with the derived haplotypes that were consistent with selection to near fixation for the haplotypes affecting fat tail size in the fat tail breed. Analysis of the candidate region on chromosome 7 indicated that selection differentiated the beneficial alleles between breeds and homozygosity has increased in the thin tail breed which also had the ancestral haplotype. These results enabled us to confirm the signature of selection in these regions and refine the critical intervals from 113kb, 201kb and 2,831kb to 28kb, 142kb and 1,006kb on chromosome 5, 7 and X respectively. These regions contain several genes associated with fat metabolism or developmental processes consisting TCF7 and PPP2CA (OAR5), PTGDR and NID2 (OAR7), AR, EBP, CACNA1F, HSD15B, SLC35A2, BMP15, WDR13 and RBM3 (OAR X), each of which could potentially be the actual target of selection. Study of core haplotypes alleles in our regions of interest also supported the hypothesis that the first domesticated sheep were thin tailed and fat tail animals were developed later. Conclusions Our results provide a comprehensive assessment of how and where selection has affected the patterns of variation in candidate regions associated with fat deposition in thin and fat tail sheep breeds. The hitchhiking mapping approach in this study was novel in the sense that most of the exploratory genome scan studies in domestic animals have not clarified the signal from the candidate regions, probably due to the lack of suitable genomic resources.