Figure 5

Mutation analysis of the MTM1 gene in affected and unaffected Rottweilers. (A) DNA sequence tracings from Sanger sequencing of a portion of MTM1 exon 11 centered on cDNA position 1151 illustrating mutation of adenine to a cytosine in a hemizygous affected puppy (middle), compared with an unaffected male littermate (bottom) and his carrier mother (top). (B) Schematic of full-length myotubularin with major domains and motifs showing the location of the wild type glutamine (Q) at position 384. (C, D) Alignments of a 30 amino acid stretch of myotubularins from different species (C), and from each of the first 13 human myotubularin related proteins (D), centered about the position of Q384. (D) The six enzymatically inactive myotubularin related proteins are separated by a space from the eight active forms. Residues constituting the phosphatase active site (P-loop) and α helix 10 are indicated by brackets above.