PMID- 23300579
OWN - NLM
STAT- MEDLINE
DCOM- 20130717
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - Partial deletion of the sulfate transporter SLC13A1 is associated with an 
      osteochondrodysplasia in the Miniature Poodle breed.
PG  - e51917
LID - 10.1371/journal.pone.0051917 [doi]
LID - e51917
AB  - A crippling dwarfism was first described in the Miniature Poodle in Great Britain 
      in 1956. Here, we resolve the genetic basis of this recessively inherited 
      disorder. A case-control analysis (8:8) of genotype data from 173 k SNPs revealed 
      a single associated locus on CFA14 (P(raw) <10(-8)). All affected dogs were 
      homozygous for an ancestral haplotype consistent with a founder effect and an 
      identical-by-descent mutation. Systematic failure of nine, nearly contiguous 
      SNPs, was observed solely in affected dogs, suggesting a deletion was the causal 
      mutation. A 130-kb deletion was confirmed both by fluorescence in situ 
      hybridization (FISH) analysis and by cloning the physical breakpoints. The 
      mutation was perfectly associated in all cases and obligate heterozygotes. The 
      deletion ablated all but the first exon of SLC13A1, a sodium/sulfate symporter 
      responsible for regulating serum levels of inorganic sulfate. Our results 
      corroborate earlier findings from an Slc13a1 mouse knockout, which resulted in 
      hyposulfatemia and syndromic defects. Interestingly, the metabolic disorder in 
      Miniature Poodles appears to share more clinical signs with a spectrum of human 
      disorders caused by SLC26A2 than with the mouse Slc13a1 model. SLC26A2 is the 
      primary sodium-independent sulfate transporter in cartilage and bone and is 
      important for the sulfation of proteoglycans such as aggregan. We propose that 
      disruption of SLC13A1 in the dog similarly causes undersulfation of proteoglycans 
      in the extracellular matrix (ECM), which impacts the conversion of cartilage to 
      bone. A co-dominant DNA test of the deletion was developed to enable breeders to 
      avoid producing affected dogs and to selectively eliminate the mutation from the 
      gene pool.
FAU - Neff, Mark W
AU  - Neff MW
AD  - Laboratory of Neurogenetics and Canine Behavior, Van Andel Research Institute, 
      Grand Rapids, MI, USA. mark.neff@vai.org
FAU - Beck, John S
AU  - Beck JS
FAU - Koeman, Julie M
AU  - Koeman JM
FAU - Boguslawski, Elissa
AU  - Boguslawski E
FAU - Kefene, Lisa
AU  - Kefene L
FAU - Borgman, Andrew
AU  - Borgman A
FAU - Ruhe, Alison L
AU  - Ruhe AL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20121226
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Sodium Sulfate Cotransporter)
RN  - 0 (Sulfates)
RN  - 0 (Symporters)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Case-Control Studies
MH  - Cation Transport Proteins/*deficiency/genetics
MH  - Cells, Cultured
MH  - DNA/genetics
MH  - Dogs
MH  - Female
MH  - *Gene Deletion
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Mice
MH  - Osteochondrodysplasias/*etiology/metabolism/pathology
MH  - Sodium Sulfate Cotransporter
MH  - Sulfates/analysis
MH  - Symporters/*deficiency/genetics
PMC - PMC3530542
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/10 06:00
MHDA- 2013/07/19 06:00
PMCR- 2012/12/26
CRDT- 2013/01/10 06:00
PHST- 2012/03/06 00:00 [received]
PHST- 2012/11/14 00:00 [accepted]
PHST- 2013/01/10 06:00 [entrez]
PHST- 2013/01/10 06:00 [pubmed]
PHST- 2013/07/19 06:00 [medline]
PHST- 2012/12/26 00:00 [pmc-release]
AID - PONE-D-12-06836 [pii]
AID - 10.1371/journal.pone.0051917 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e51917. doi: 10.1371/journal.pone.0051917. Epub 2012 Dec 26.