Fig 3. The SLIT1 gene harbours an associated haplotype in Shar-Pei and fixed blocks in German shepherd.

(A) In SP, four SNPs (grey circles) suggestively associated to IgA levels, were located within the first intron of SLIT1. (B) A distinct increase in the degree of genetic differentiation (F_ST) between dogs and wolves span a 75 kb region (windows with F_ST >0.67 are coloured in black) within the SLIT1 locus, with F_ST values of two consecutive 50 kb windows reaching 0.68 and 0.67, respectively (windows with F_ST >0.43 are coloured in grey). More extreme genetic differentiation was only seen in 7% of the whole dog genome, potentially indicating that IgA levels may have been affected in a pleiotropic manner by primary selection affecting another primary target (such as brain function) during dog domestication. Blocks of fixation were identified in GSD, spanning several regulatory sites including binding sites for the transcription factor CTCF. (C) The top SNPs in SP were in high LD (r² >0.8) and phased into four haplotypes where two were common (1 and 4) and two were rare (2 and 3). Dogs homozygous for 1/1 had significantly higher IgA levels compared to dogs homozygous for 4 (4/4) and heterozygous 4/1 (p = 0.0005 and p = 0.03, respectively). Additionally, homozygous 4/4 had significantly lower IgA levels than heterozygous 4/1 (p = 0.006) indicating an additive effect of the risk and/or protective haplotype.