Figure 1

<p>Comparative Sequence Analysis of the <i>GLI3</i> Locus Detects Conserved Non-coding Sequence Elements. (A) Sequence alignments of the genomic interval containing the human <i>GLI3</i> locus and flanking human genes <i>INHBA</i> and <i>PSMA2</i> with orthologous counterparts from representative members of rodent, bird, amphibian, and fish lineages. These are shown as SLAGAN derived VISTA representations. Conserved coding sequences are depicted in blue and conserved non-coding sequences are in pink. Criteria of alignment were 60 bp window and 50% conservation cutoff. Conservation between human and <i>Fugu</i> (scaffold_210 ENSEMBL genome browser) is restricted to the <i>GLI3</i> gene. Red bars above the conservation plot depict the approximate length of intergenic regions flanking human <i>GLI3.</i> The blue arrow shows the length of the <i>GLI3</i> gene and the direction of transcription. A graphic representation showing exons and introns of <i>GLI3</i> is shown below the homology plot. Green vertical lines indicate the positions of alterations affecting the genomic structure of the locus which result in loss of GLI3 function: a translocation event associated with Greig cephalopolysyndactyly syndrome (GCPS) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000366#pone.0000366-Kruger1" target="_blank">[36]</a>, and two insertions (ins) in mouse mutants anterior digit pattern deformity (<i>add</i>) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000366#pone.0000366-Pohl1" target="_blank">[7]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000366#pone.0000366-vanderHoeven1" target="_blank">[37]</a> and polydactyly Nagoya (<i>Pdn</i>) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000366#pone.0000366-Ueta1" target="_blank">[38]</a>. (B) Magnified view of the human/<i>Fugu</i> conservation plot and the genomic structure of human <i>GLI3</i>. The red vertical bars below the plot show the position of human/<i>Fugu</i> highly conserved non-coding sequence elements (CNEs) that were functionally tested as putative enhancers.