HLA class II haplotype and sequence analysis support a role for DQ in narcolepsy

Abstract

A systematic haplotype and sequencing analysis of the HLA -DR and - DQ region in patients with narcolepsy was performed. Five new (CA) n microsatellite markers were generated and positioned on the physical map across the HLA -DQB1-DQA1-DRB1 interval. Haplotypes for these new markers and the three HLA loci were established using somatic cell hybrids generated from patients. A four-marker haplotype surrounding the DQB1 * 0602 gene was found in all narcolepsy patients, and was identical to haplotypes observed on random chromosomes harboring the DQB1 * 0602 allele. Eighty-six kilobases of contiguous genomic sequence across the region did not reveal new genes, and analysis of this sequence for single nucleotide polymorphisms did not reveal sequence variation among DQB1 * 0602 chromosomes. These results are consistent with other studies, suggesting that the HLA -DQ genes themselves are among the predisposing factors in narcolepsy.