IgH (mu-switch and gamma-1) region restriction fragment length polymorphism in human narcolepsy

Abstract

Predisposition to narcolepsy involves genetic factors both in humans and in a canine model of the disorder. In humans, narcolepsy is strongly associated with HLA DR15 and DQB1*0602. In Dobermans and Labradors, narcolepsy is transmitted as a single autosomal recessive gene with full penetrance (canarc-1). Canine narcolepsy is not linked with DLA, the canine equivalent of HLA, but co-segregates with a DNA segment with high homology with the mu immunoglobulin heavy-chain (IgH) switch-like region (S mu). To determine if the IgH locus is involved in genetic predisposition to human narcolepsy, restriction fragment length polymorphisms specific for the IgM and IgG cluster within this locus were studied in sporadic cases of the disease, as well as in five families with two or more affected individuals. Comparisons were made between control populations and both familial and sporadic cases and for patients with and without HLA-DR15 and DQB1*0602. RFLP analysis at the S mu and gamma-1 loci, which cover over 200 kb of 14q32.3, indicates that there is no evidence for any association between the IgH region and human narcolepsy.