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Fig. 1. A zebrafish sox10 homologue maps to the region of the cls locus. (A) Sequence comparison of predicted zebrafish Sox10 homologue (44, 45 and 60% identity to mouse Sox8, Sox9 and Sox10, respectively). Blocks of identity corresponding to all proposed functional domains can be seen, including the HMG domain (red underline; 95% amino acid identity), N-terminal synergy domain (1-105; 48% identity), dimerisation domain (66-105; 78% identity), C-terminal transcriptional activation domain (395-485; 76% identity) and a domain C-terminal to the HMG domain corresponding to a putative protein-protein interaction domain (234-325; 64% identity) (Bondurand et al., 2000; Kuhlbrodt et al., 1998a; Kuhlbrodt et al., 1998b; Liu et al., 1999; Peirano and Wegner, 2000). (B) Maximum likelihood phylogenetic tree of subgroup E Sox genes. Zebrafish sox10 clusters within the Sox10 clade of vertebrate Sox genes. The Accession Numbers for the sequences are as follows: chicken Sox8 (AF228664); trout SoxP1 (D83256); mouse Sox8 (AF191325); human SOX8 (AF226675); frog Sox9a (AB035887); alligator Sox9 (AF106572); trout Sox9 (AB006448); zebrafish sox9a (AF277096); zebrafish sox9b (AF277097); chicken Sox9 (AB012236); pig Sox9 (AF029696); human SOX9 (Z46629); zebrafish sox10 (AF402677); chicken Sox10 (AF152356); mouse Sox10 (AF047389); rat Sox10 (AJ001029); human SOX10 (NM_006941). (C) Mapping using the LN54 panel placed sox10 on LG 3 in the region of the cls locus identified using microsatellite markers (we found four recombinants between cls and z13387 in 274 meioses). Note that z8492 was not polymorphic and could not be analysed in the mapping cross. (D) Schematic to illustrate changes in Sox10 mutant proteins. In clsm618 a T425A substitution results in a non-conservative change (Leu142Gln) within the HMG domain (red). In clstw2 and clstw11, a A1126T substitution introduced a Stop codon truncating the protein just N-terminal to the transactivation domain (blue). Insertion of a 1.4 kb transposon at the site indicated by the arrow in A disrupts sox10 in clst3 and introduces a C-terminal extension of eight novel amino acids before premature truncation N-terminal to the HMG domain (yellow). (E) Chromatogram traces to show nucleotide changes affecting sox10-coding regions in clsm618 and clstw2.