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A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs

Figure 2

The association with Shar-Pei Fever susceptibility and the strongest selective sweep signal co-localize on chromosome 13.

(A) A 10-fold reduction of heterozygosity was identified on chromosome 13 when comparing Shar-Pei (n = 50) to 24 other canine breeds (n = 230). 50,000 SNPs were used to screen the whole genome using a sliding window approach (see Materials and Methods). (B) A case-control genome-wide association analysis identified a strong peak with several SNPs on chromosome 13 to be in association with Familial Shar-Pei Fever (FSF). After correcting for stratification and multiple testing (100,000 permutations), four SNPs retained significant association (p<0.05; strongest SNP association, CanFam 2.0 chr13: 27,913,803 Mb). Shar-Pei dogs used in the study were strictly classified into groups of affected (n = 22) and unaffected (n = 17) by FSF. (C) SNPs associated with FSF (blue line) are interspersed with the signals of selection (red line). The 39 Shar-Pei and 17,227 SNP common to both analyses were used to generate this graph.

Figure 2