HLA CLASS-II HAPLOTYPE AND SEQUENCE-ANALYSIS SUPPORT A ROLE FOR DQ INNARCOLEPSY

A systematic haplotype and sequencing analysis of the HLA-DR and -DQ r egion in patients with narcolepsy was performed. Five new (CA)(n) micr osatellite markers were generated and positioned on the physical map a cross the HLA-DQB1-DQA1-DRB1 interval, Haplotypes for these new marker s and the three HLA loci were established using somatic cell hybrids g enerated from patients. A four-marker haplotype surrounding the DQB10 602 gene was found in all narcolepsy patients, and was identical to ha plotypes observed on random chromosomes harboring the DQB10602 allele . Eighty-six kilobases of contiguous genomic sequence across the regio n did not reveal new genes, and analysis of this sequence for single n ucleotide polymorphisms did not reveal sequence variation among DQB10 602 chromosomes. These results are consistent with other studies, sugg esting that the HLA-DQ genes themselves are among the predisposing fac tors in narcolepsy.