Figure 2. Genetic mapping identified a loss of function allele of Katnal1 as the causal genetic lesion.

Genome-wide SNP linkage analysis identified a single region of distal chromosome 5 as the site of the causal mutation. Quantitative RT-PCR analysis and DNA sequencing analysis of genes within the critical region identified a single point mutational change (Thymine to Guanine) within exon seven of the gene encoding the putative microtubule severing protein Katnal1 (a, b) (The mutated allele was designated Katnal1^1H). The point mutation within Katnal1^1H generates a Leucine to Valine substitution at residue 286, within the conserved ATPase AAA-Core domain of the KATNAL1 protein (a, b). (c) Comparative genome analysis of KATNAL1 peptide sequence across diverse species demonstrated complete conservation of the Leucine residue for at least 400 million years.