genetic cause of Dalmatian hyperuricosuria & hyperuricaemia
Geplaatst: do 13 nov 2008, 15:07
kreeg deze mail, misschien iets voor de geintresseerde dalmaten eigenaren?
Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the
Dog
Danika Bannasch, Noa Safra, Amy Young, Nili Karmi, R. S. Schaible, G. V.
Ling
Abstract
Allantoin is the end product of purine catabolism in all mammals except
humans, great apes, and one breed of dog, the Dalmatian. Humans and
Dalmatian dogs produce uric acid during purine degradation, which leads to
elevated levels of uric acid in blood and urine and can result in
significant diseases in both species. The defect in Dalmatians results from
inefficient transport of uric acid in both the liver and renal proximal
tubules. Hyperuricosuria and hyperuricemia (huu) is a simple autosomal
recessive trait for which all Dalmatian dogs are homozygous. Therefore, in
order to map the locus, an interbreed backcross was used. Linkage mapping
localized the huu trait to CFA03, which excluded the obvious urate
transporter 1 gene, SLC22A12. Positional cloning placed the locus in a
minimal interval of 2.5 Mb with a LOD score of 17.45. A critical interval of
333 kb containing only four genes was homozygous in all Dalmatians. Sequence
and expression analyses of the SLC2A9 gene indicated three possible
mutations, a missense mutation (G616T;C188F) and two promoter mutations that
together appear to reduce the expression levels of one of the isoforms. The
missense mutation is associated with hyperuricosuria in the Dalmatian, while
the promoter SNPs occur in other unaffected breeds of dog. Verification of
the causative nature of these changes was obtained when hyperuricosuric dogs
from several other breeds were found to possess the same combination of
mutations as found in the Dalmatian. The Dalmatian dog model of
hyperuricosuria and hyperuricemia underscores the importance of SLC2A9 for
uric acid transport in mammals.
full text available fee online from:
http://www.plosgenetics.org/article/inf ... en.1000246
Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the
Dog
Danika Bannasch, Noa Safra, Amy Young, Nili Karmi, R. S. Schaible, G. V.
Ling
Abstract
Allantoin is the end product of purine catabolism in all mammals except
humans, great apes, and one breed of dog, the Dalmatian. Humans and
Dalmatian dogs produce uric acid during purine degradation, which leads to
elevated levels of uric acid in blood and urine and can result in
significant diseases in both species. The defect in Dalmatians results from
inefficient transport of uric acid in both the liver and renal proximal
tubules. Hyperuricosuria and hyperuricemia (huu) is a simple autosomal
recessive trait for which all Dalmatian dogs are homozygous. Therefore, in
order to map the locus, an interbreed backcross was used. Linkage mapping
localized the huu trait to CFA03, which excluded the obvious urate
transporter 1 gene, SLC22A12. Positional cloning placed the locus in a
minimal interval of 2.5 Mb with a LOD score of 17.45. A critical interval of
333 kb containing only four genes was homozygous in all Dalmatians. Sequence
and expression analyses of the SLC2A9 gene indicated three possible
mutations, a missense mutation (G616T;C188F) and two promoter mutations that
together appear to reduce the expression levels of one of the isoforms. The
missense mutation is associated with hyperuricosuria in the Dalmatian, while
the promoter SNPs occur in other unaffected breeds of dog. Verification of
the causative nature of these changes was obtained when hyperuricosuric dogs
from several other breeds were found to possess the same combination of
mutations as found in the Dalmatian. The Dalmatian dog model of
hyperuricosuria and hyperuricemia underscores the importance of SLC2A9 for
uric acid transport in mammals.
full text available fee online from:
http://www.plosgenetics.org/article/inf ... en.1000246
