PMID- 11923913
OWN - NLM
STAT- MEDLINE
DCOM- 20020523
LR  - 20240411
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 70
IP  - 5
DP  - 2002 May
TI  - Genetic dissection of the human leukocyte antigen region by use of haplotypes of 
      Tasmanians with multiple sclerosis.
PG  - 1125-37
AB  - Association of multiple sclerosis (MS) with the human leukocyte antigen (HLA) 
      class II haplotype DRB1*1501-DQB1*0602 is the most consistently replicated 
      finding of genetic studies of the disease. However, the high level of linkage 
      disequilibrium (LD) in the HLA region has hindered the identification of other 
      loci that single-marker tests for association are unlikely to resolve. In order 
      to address this issue, we generated haplotypes spanning 14.754 Mb (5 cM) across 
      the entire HLA region. The haplotypes, which were inferred by genotyping 
      relatives of 152 patients with MS and 105 unaffected control subjects of 
      Tasmanian ancestry, define a genomic segment from D6S276 to D6S291, including 13 
      microsatellite markers integrated with allele-typing data for DRB1 and DQB1. 
      Association to the DRB1*1501-DQB1*0602 haplotype was replicated. In addition, we 
      found that the class I/extended class I region, defined by a genomic segment of 
      approximately 400 kb between MOGCA and D6S265, harbors genes that independently 
      increase risk of, or provide protection from, MS. Log-linear modeling analysis of 
      constituent haplotypes that represent genomic regions containing class I 
      (MOGCA-D6S265), class III (TNFa-TNFd-D6S273), and class II (DRB1-DQB1) genes 
      indicated that having class I and class II susceptibility variants on the same 
      haplotype provides an additive effect on risk. Moreover, we found no evidence for 
      a disease locus in the class III region defined by a 150-kb genomic segment 
      containing the TNF locus and 14 other genes. A global overview of LD performed 
      using GOLD identified two discrete blocks of LD in the HLA region that correspond 
      well with previous findings. We propose that the analysis of haplotypes, by use 
      of the types of approaches outlined in the present article, should make it 
      possible to more accurately define the contribution of the HLA to MS.
FAU - Rubio, Justin P
AU  - Rubio JP
AD  - Walter and Eliza Hall Institute of Medical Research, and Cooperative Research 
      Centre for Discovery of Genes for Common Human Diseases, Melbourne, Victoria, 
      Australia. rubio@wehi.edu.au
FAU - Bahlo, Melanie
AU  - Bahlo M
FAU - Butzkueven, Helmut
AU  - Butzkueven H
FAU - van Der Mei, Ingrid A F
AU  - van Der Mei IA
FAU - Sale, Michele M
AU  - Sale MM
FAU - Dickinson, Joanne L
AU  - Dickinson JL
FAU - Groom, Patricia
AU  - Groom P
FAU - Johnson, Laura J
AU  - Johnson LJ
FAU - Simmons, Rex D
AU  - Simmons RD
FAU - Tait, Brian
AU  - Tait B
FAU - Varney, Mike
AU  - Varney M
FAU - Taylor, Bruce
AU  - Taylor B
FAU - Dwyer, Terence
AU  - Dwyer T
FAU - Williamson, Robert
AU  - Williamson R
FAU - Gough, Nicholas M
AU  - Gough NM
FAU - Kilpatrick, Trevor J
AU  - Kilpatrick TJ
FAU - Speed, Terence P
AU  - Speed TP
FAU - Foote, Simon J
AU  - Foote SJ
LA  - eng
SI  - OMIM/126200
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20020329
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Genetic Markers)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-D Antigens)
SB  - IM
MH  - Alleles
MH  - Case-Control Studies
MH  - Chromosome Mapping
MH  - Female
MH  - Gene Frequency/genetics
MH  - Genetic Markers/genetics
MH  - Genetic Predisposition to Disease/genetics
MH  - HLA Antigens/*genetics
MH  - HLA-D Antigens/genetics
MH  - Haplotypes/*genetics
MH  - Humans
MH  - Leukocytes/*metabolism
MH  - Linkage Disequilibrium/genetics
MH  - Major Histocompatibility Complex/genetics
MH  - Male
MH  - Models, Genetic
MH  - Multiple Sclerosis/*genetics
MH  - Odds Ratio
MH  - Software
MH  - Tasmania/epidemiology
PMC - PMC447590
EDAT- 2002/04/02 10:00
MHDA- 2002/05/25 10:01
PMCR- 2002/11/01
CRDT- 2002/04/02 10:00
PHST- 2001/12/03 00:00 [received]
PHST- 2002/01/28 00:00 [accepted]
PHST- 2002/04/02 10:00 [pubmed]
PHST- 2002/05/25 10:01 [medline]
PHST- 2002/04/02 10:00 [entrez]
PHST- 2002/11/01 00:00 [pmc-release]
AID - S0002-9297(07)62508-7 [pii]
AID - 013595 [pii]
AID - 10.1086/339932 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2002 May;70(5):1125-37. doi: 10.1086/339932. Epub 2002 Mar 29.