Genetic linkage of autosomal recessive canine narcolepsy with a mu immunoglobulin heavy-chain switch-like segment.
Identification of genes determining narcolepsy susceptibility is important not only for understanding that disorder but also for possible clues to general sleep-control mechanisms. Studies in humans reveal at least one such gene related to the major histocompatibility complex and in dog an as-yet-unmapped single, autosomal recessive gene canarc-1. Gene markers for canarc-1 were therefore sought by DNA restriction fragment length polymorphisms in our colony of narcoleptic dogs. A human mu-switch immunoglobulin probe and the enzyme Hae III identified a gene cosegregating with canarc-1 in backcrossed animals (logarithm of odds scores: m = 24, Z max = 7.2 at theta = 0%). canarc-1 was also shown not to be tightly linked with the dog major histocompatibility complex (m = 40, Z less than -2 at theta less than 4.8%). These results represent the mapping of a non-major histocompatibility complex narcolepsy gene and strongly suggest involvement of the immune system in the pathophysiology of that disease.
Mignot
E
E
Sleep Disorders Research Center, Stanford University School of Medicine, Palo Alto, CA 94304.
Wang
C
C
Rattazzi
C
C
Gaiser
C
C
Lovett
M
M
Guilleminault
C
C
Dement
W C
WC
Grumet
F C
FC
D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005803:Genes, Immunoglobulin; D005808:Genes, Recessive; D005812:Genes, Switch; D008040:Genetic Linkage; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D008285:Major Histocompatibility Complex; D009290:Narcolepsy / Q000235:genetics / Q000662:veterinary*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
D007148:Immunoglobulin mu-Chains