PMID- 10053014
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 64
IP  - 3
DP  - 1999 Mar
TI  - The predisposition to type 1 diabetes linked to the human leukocyte antigen 
      complex includes at least one non-class II gene.
PG  - 793-800
AB  - The human leukocyte antigen (HLA) complex, encompassing 3.5 Mb of DNA from the 
      centromeric HLA-DPB2 locus to the telomeric HLA-F locus on chromosome 6p21, 
      encodes a major part of the genetic predisposition to develop type 1 diabetes, 
      designated "IDDM1." A primary role for allelic variation of the class II 
      HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci has been established. However, studies of 
      animals and humans have indicated that other, unmapped, major histocompatibility 
      complex (MHC)-linked genes are participating in IDDM1. The strong linkage 
      disequilibrium between genes in this complex makes mapping a difficult task. In 
      the present paper, we report on the approach we have devised to circumvent the 
      confounding effects of disequilibrium between class II alleles and alleles at 
      other MHC loci. We have scanned 12 Mb of the MHC and flanking chromosome regions 
      with microsatellite polymorphisms and analyzed the transmission of these marker 
      alleles to diabetic probands from parents who were homozygous for the alleles of 
      the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes. Our analysis, using three independent 
      family sets, suggests the presence of an additional type I diabetes gene (or 
      genes). This approach is useful for the analysis of other loci linked to common 
      diseases, to verify if a candidate polymorphism can explain all of the 
      association of a region or if the association is due to two or more loci in 
      linkage disequilibrium with each other.
FAU - Lie, B A
AU  - Lie BA
AD  - Institute of Transplantation Immunology, The National Hospital, 0027 Oslo, 
      Norway. b.a.lie@labmed.uio.no
FAU - Todd, J A
AU  - Todd JA
FAU - Pociot, F
AU  - Pociot F
FAU - Nerup, J
AU  - Nerup J
FAU - Akselsen, H E
AU  - Akselsen HE
FAU - Joner, G
AU  - Joner G
FAU - Dahl-Jorgensen, K
AU  - Dahl-Jorgensen K
FAU - Ronningen, K S
AU  - Ronningen KS
FAU - Thorsby, E
AU  - Thorsby E
FAU - Undlien, D E
AU  - Undlien DE
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (HLA Antigens)
SB  - IM
CIN - Am J Hum Genet. 2000 Apr;66(4):1468. PMID: 10739775
MH  - Alleles
MH  - Case-Control Studies
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Exons
MH  - Genes, MHC Class II/genetics
MH  - Genetic Predisposition to Disease
MH  - HLA Antigens/*genetics
MH  - Histocompatibility Testing
MH  - Humans
MH  - Microsatellite Repeats
MH  - Models, Statistical
MH  - Polymorphism, Genetic
PMC - PMC1377797
EDAT- 1999/03/03 03:04
MHDA- 2000/03/21 09:00
PMCR- 1999/09/01
CRDT- 1999/03/03 03:04
PHST- 1999/03/03 03:04 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/03/03 03:04 [entrez]
PHST- 1999/09/01 00:00 [pmc-release]
AID - S0002-9297(07)61717-0 [pii]
AID - 10.1086/302283 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Mar;64(3):793-800. doi: 10.1086/302283.