PMID- 11132147
OWN - NLM
STAT- MEDLINE
DCOM- 20010118
LR  - 20190831
IS  - 0093-7711 (Print)
IS  - 0093-7711 (Linking)
VI  - 52
IP  - 1-2
DP  - 2000 Nov
TI  - Identification of a telomeric boundary of the HLA region with potential for 
      predisposition to human narcolepsy.
PG  - 12-8
AB  - We report on a study performed to determine a boundary of the region with the 
      potential to contribute to the predisposition to human narcolepsy (the 
      susceptibility region) in the human leukocyte antigen (HLA) region. We 
      investigated a Japanese narcolepsy family, in which a de novo chromosomal 
      recombination occurred between the HLA-DRB1 and HLA-B genes in the proband. The 
      recombinant chromosome carrying HLA-DRB1*1501 was transmitted to the affected 
      child and grandchild, suggesting that a strong genetic factor(s) predisposing to 
      the disorder was (were) present on the chromosome, and that the recombination 
      breakpoint could be regarded as a boundary to the susceptibility region. To 
      search for the breakpoint, we carried out allele typing at various polymorphic 
      sites, e.g., microsatellite repeat polymorphisms, restriction fragment length 
      polymorphisms, and single-nucleotide polymorphisms in the HLA region, and 
      examined haplotypes with the polymorphic sites in the family members. Haplotype 
      analyses revealed that the recombination breakpoint was present approximately 50 
      kb to the telomeric side of the palmitoyl-protein thioesterase-2 (PPT2) gene in 
      the HLA class III region. From the gene map of the HLA region, the cyclic AMP 
      response element-binding protein-related protein gene (CREB-RP) appeared to be 
      located at the telomeric end in the 50-kb region. Therefore, the data presented 
      here suggest that the susceptibility region for the disorder in the family is 
      present on the centromeric side of the CREB-RP gene in the recombinant Chromosome 
      6 carrying HLA-DRB1*1501.
FAU - Miyagawa, T
AU  - Miyagawa T
AD  - Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 
      Japan.
FAU - Hohjoh, H
AU  - Hohjoh H
FAU - Honda, Y
AU  - Honda Y
FAU - Juji, T
AU  - Juji T
FAU - Tokunaga, K
AU  - Tokunaga K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Immunogenetics
JT  - Immunogenetics
JID - 0420404
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (NOTCH4 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptor, Notch4)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Notch)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Female
MH  - Genetic Predisposition to Disease/genetics
MH  - HLA Antigens/*genetics
MH  - HLA-B Antigens/genetics
MH  - HLA-DR Antigens/genetics
MH  - HLA-DRB1 Chains
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Microsatellite Repeats
MH  - Narcolepsy/*genetics
MH  - Pedigree
MH  - Polymorphism, Genetic
MH  - Proto-Oncogene Proteins/genetics
MH  - Receptor, Notch4
MH  - *Receptors, Cell Surface
MH  - Receptors, Notch
MH  - Recombination, Genetic
MH  - Telomere/*genetics
MH  - Thiolester Hydrolases/genetics
EDAT- 2000/12/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/12/29 11:00
PHST- 2000/12/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/12/29 11:00 [entrez]
AID - 10.1007/s002510000245 [doi]
PST - ppublish
SO  - Immunogenetics. 2000 Nov;52(1-2):12-8. doi: 10.1007/s002510000245.