PMID- 12215900
OWN - NLM
STAT- MEDLINE
DCOM- 20030430
LR  - 20101118
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 3 Suppl 1
DP  - 2002 Oct
TI  - Genome scan stratified by the presence of anti-double-stranded DNA (dsDNA) 
      autoantibody in pedigrees multiplex for systemic lupus erythematosus (SLE) 
      establishes linkages at 19p13.2 (SLED1) and 18q21.1 (SLED2).
PG  - S35-41
AB  - Anti-double-stranded DNA (anti-dsDNA) is arguably one of the most specific 
      autoantibodies in systemic lupus erythematosus (SLE). This antibody is associated 
      with more severe SLE and with glomerulonephritis. From 196 pedigrees multiplex 
      for SLE, we selected those that had any SLE affected positive for anti-dsDNA by 
      the Crithidia luciliae kinetoplast imunofluorescence assay. This stratification 
      strategy tested the hypothesis that anti-dsDNA would identify a more genetically 
      homogeneous group of pedigrees, in which previously undetected linkage effects 
      could be established. A genome screen data for linkage to SLE was available at 
      307 microsatellite markers for this selected group of 71 pedigrees: 37 
      European-American, 29 African-American, and five others. The most significant 
      results were obtained at 19p13.2 (LOD(max) = 4.93), named SLED1, in the 37 
      European-American pedigrees using a dominant model with mixed penetrances (92% 
      for females and 49% for males) at 100% homogeneity (theta = 0). A second linkage 
      effect, SLED2, was established in the 29 African-American pedigrees at 18q21.1 
      (LOD(max) = 3.40) using a recessive model with 100% penetrance (theta = 0.1). 
      Parametric and non-parametric multipoint analyses were performed, which provided 
      further evidence and support of susceptibility genes residing in these regions. 
      In conclusion, two powerful linkages have been detected with SLE based on the 
      presence of anti-dsDNA. These findings show SLE to be a richly complicated 
      disease phenotype that is now ripe for important new discovery through a genetic 
      approach.
FAU - Namjou, B
AU  - Namjou B
AD  - Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, 
      OK 73104, USA.
FAU - Nath, S K
AU  - Nath SK
FAU - Kilpatrick, J
AU  - Kilpatrick J
FAU - Kelly, J A
AU  - Kelly JA
FAU - Reid, J
AU  - Reid J
FAU - Reichlin, M
AU  - Reichlin M
FAU - James, J A
AU  - James JA
FAU - Harley, J B
AU  - Harley JB
LA  - eng
GR  - AI24717/AI/NIAID NIH HHS/United States
GR  - AI31584/AI/NIAID NIH HHS/United States
GR  - AR12253/AR/NIAMS NIH HHS/United States
GR  - AR42460/AR/NIAMS NIH HHS/United States
GR  - AR45231/AR/NIAMS NIH HHS/United States
GR  - RR15577/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (Antibodies)
RN  - 0 (Autoantibodies)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Antibodies/blood
MH  - Autoantibodies/*immunology
MH  - *Chromosomes, Human, Pair 18
MH  - *Chromosomes, Human, Pair 19
MH  - Crithidia/immunology
MH  - DNA/*immunology
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Genetic Linkage
MH  - Humans
MH  - Lod Score
MH  - Lupus Erythematosus, Systemic/*genetics/*immunology
MH  - Male
MH  - Pedigree
EDAT- 2002/09/07 10:00
MHDA- 2003/05/06 05:00
CRDT- 2002/09/07 10:00
PHST- 2001/12/18 00:00 [received]
PHST- 2002/05/15 00:00 [revised]
PHST- 2002/05/15 00:00 [accepted]
PHST- 2002/09/07 10:00 [pubmed]
PHST- 2003/05/06 05:00 [medline]
PHST- 2002/09/07 10:00 [entrez]
AID - 10.1038/sj.gene.6363905 [doi]
PST - ppublish
SO  - Genes Immun. 2002 Oct;3 Suppl 1:S35-41. doi: 10.1038/sj.gene.6363905.