A mutation in the CLN8 gene in English Setter dogs with neuronal ceroid-lipofuscinosis.
A heritable neurodegenerative disease of English Setters has long been studied as a model of human neuronal ceroid-lipofuscinosis (NCL). Megablast searches of the first build of the canine genome for potential causative genes located the CLN8 gene near the q telomere of canine chromosome 37, close to a marker previously linked to English Setter NCL. Sequence analysis of the coding region from affected dogs revealed a T-to-C transition in the CLN8 gene that predicts a p.L164P missense mutation. Leucine 164 is conserved in four other mammalian species. The C allele co-segregated with the disease phenotype in a two-generation English Setter family in a pattern consistent with autosomal recessive inheritance. All four NCL-affected family members were C/C homozygotes and all four obligate carriers were C/T heterozygotes; whereas, 103 unrelated dogs were all T/T homozygotes. These findings indicate that the CLN8 T-to-C transition is the likely cause of English Setter NCL.
Katz
Martin L
ML
Mason Eye Institute, University of Missouri School of Medicine, Columbia, MO, USA.
Khan
Shahnawaz
S
Awano
Tomoyuki
T
Shahid
S Adam
SA
Siakotos
Aristotle N
AN
Johnson
Gary S
GS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D033481:Chromosomes, Mammalian / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D010375:Pedigree; D020161:Physical Chromosome Mapping; D016415:Sequence Alignment
D008565:Membrane Proteins