HLA class II haplotype and sequence analysis support a role for DQ in narcolepsy.
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.
Ellis
M C
MC
Mercator Genetics, Inc., 4040 Campbell Ave., Menlo Park, CA 94025, USA.
Hetisimer
A H
AH
Ruddy
D A
DA
Hansen
S L
SL
Kronmal
G S
GS
McClelland
E
E
Quintana
L
L
Drayna
D T
DT
Aldrich
M S
MS
Mignot
E
E
D015984:Causality; D002874:Chromosome Mapping; D005819:Genetic Markers; D015698:Genomic Library; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D018895:Microsatellite Repeats; D009290:Narcolepsy / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
D005819:Genetic Markers; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen