Figure 1.
Identification of locus responsible for FIS by genome-wide association scan.
(A) Manhattan plot of association test results showing the chromosome locations of the 42,536 SNPs which passed quality control against –log10(P). The red line indicates the threshold for genome-wide significance after Bonferroni correction for multiple testing (Praw = 1.2×10−6), which corresponds to an alpha value of 0.05. (B) Focus on region of ECA26 that shows FIS association. The vertical broken lines indicate the region (29.6–32.2 Mb) which was investigated further by fine-mapping.
Figure 2.
SNP haplotypes and genes from the region of ECA26 genetically linked and associated with FIS.
(A) The affected SNP haplotype is shown on the left. The affected alleles for three key microsatellite markers are also included. The extent of conserved affected haplotypes present in the 13 affected individuals (A1–13) are indicated with blue bars. Accession numbers (newly identified SNPs) or the local SNP ID number (http://www.broadinstitute.org/ftp/distribution/horse_snp_release/v2/), together with the genome position are given. The minimal 992 kb shared region of homozygosity (29,825 – 30,817 kb) is out-lined in orange. (B) The positions of the 14 ENSEMBL annotated genes within the conserved block are indicated.
Figure 3.
SLC5A3 amino acid sequences alignments in the region of the FIS mutation.
The amino acid affected by the mutation, indicated with an arrow, is conserved in all placental mammals now sequenced with high coverage (n = 11); the top panel shows alignments of this gene region in a selection of these mammals. The bottom panel shows alignments of this region with other members of the SLC5 gene family in the horse which show structural similarity; the amino acid affected by the mutation is conserved in all of these members.