Partial Deletion of the Sulfate Transporter SLC13A1 Is Associated with an Osteochondrodysplasia in the Miniature Poodle Breed

• DOI: 10.1371/journal.pone.0051917
• Publication Date: 2012-12-26T22:12:33Z
• Authors: Mark W. Neff; John S. Beck; Julie M. Koeman; Elissa Boguslawski; Lisa Kefene; Andrew Borgman; Alison L. Ruhe
• Keywords: Male; 0303 health sciences; Symporters; Sulfates; Science; Q; R; DNA; Osteochondrodysplasias; Mice; 03 medical and health sciences; Dogs; Case-Control Studies; Medicine; Animals; Humans; Female; Cation Transport Proteins; Cells, Cultured; Gene Deletion; In Situ Hybridization, Fluorescence; Research Article; Sodium Sulfate Cotransporter

A crippling dwarfism was first described in the Miniature Poodle Great Britain 1956. Here, we resolve genetic basis of this recessively inherited disorder. case-control analysis (8∶8) genotype data from 173 k SNPs revealed a single associated locus on CFA14 (Praw <10–8). All affected dogs were homozygous for an ancestral haplotype consistent with founder effect and identical-by-descent mutation. Systematic failure nine, nearly contiguous SNPs, observed solely dogs, suggesting deletion causal 130-kb confirmed both by fluorescence situ hybridization (FISH) cloning physical breakpoints. The mutation perfectly all cases obligate heterozygotes. ablated but exon SLC13A1, sodium/sulfate symporter responsible regulating serum levels inorganic sulfate. Our results corroborate earlier findings Slc13a1 mouse knockout, which resulted hyposulfatemia syndromic defects. Interestingly, metabolic disorder Poodles appears to share more clinical signs spectrum human disorders caused SLC26A2 than model. is primary sodium-independent sulfate transporter cartilage bone important sulfation proteoglycans such as aggregan. We propose that disruption SLC13A1 dog similarly causes undersulfation extracellular matrix (ECM), impacts conversion bone. co-dominant DNA test developed enable breeders avoid producing selectively eliminate gene pool.