A genome-wide screen for linkage in Nordic sib-pairs with multiple sclerosis

被引:59
作者
Akesson, E [1 ]
Oturai, A
Berg, J
Fredrikson, S
Andersen, O
Harbo, HF
Laaksonen, M
Myhr, KM
Nyland, HI
Ryder, LP
Sandberg-Wollheim, M
Sorensen, PS
Spurkland, A
Svejgaard, A
Holmans, P
Compston, A
Hillert, J
Sawcer, S
机构
[1] Huddinge Univ Hosp, Dept Neurol, Karolinska Inst, S-14186 Huddinge, Sweden
[2] Univ Cambridge, Addenbrookes Hosp, Neurol Unit, Cambridge CB2 2QQ, England
[3] Copenhagen Univ Hosp, Dept Neurol, Rigshosp, Copenhagen, Denmark
[4] Sahlgrenska Hosp, Inst Clin Neurosci, Gothenburg, Sweden
[5] Univ Oslo, Natl Hosp, Inst Immunol, Oslo, Norway
[6] Univ Turku, Turku Immunol Ctr, SF-20500 Turku, Finland
[7] Univ Turku, Dept Virol, SF-20500 Turku, Finland
[8] Haukeland Univ Hosp, Dept Neurol, N-5021 Bergen, Norway
[9] Copenhagen Univ Hosp, Dept Clin Immunol, Rigshosp, Copenhagen, Denmark
[10] Univ Lund Hosp, Dept Neurol, S-22185 Lund, Sweden
[11] Inst Publ Hlth, MRC, Biostat Unit, Cambridge, England
基金
英国医学研究理事会;
关键词
multiple sclerosis; linkage; susceptibility gene;
D O I
10.1038/sj.gene.6363866
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Genetic factors influence susceptibility to multiple sclerosis but the responsible genes remain largely undefined, association with MHC class II alleles being the only established genetic feature of the disease. The Nordic countries have a high prevalence of multiple sclerosis, and to further explore the genetic background of the disease, we have carried out a genome-wide screen for linkage in 136 sibling-pairs with multiple sclerosis from Denmark, Finland, Norway and Sweden by typing 399 microsatellite markers. Seventeen regions where the lod score exceeds the nominal 5% significance threshold (0.7) were identified-1q11-24, 2q24-32, 3p26.3, 3q21.1, 4q12, 6p25.3, 6p21-22, 6q21, 9q34.3, 10p15, 10p12-13, 11p15.5, 12q21.3, 16p13.3, 17q25.3, 22q12-13 and Xp22.3. Although none of these regions reaches the level of genome-wide significance, the number observed exceeds the 10 that would be expected by chance alone. Our results significantly add to the growing body of linkage data relating to multiple sclerosis.
引用
收藏
页码:279 / 285
页数:7
相关论文
共 41 条
  • [1] Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases
    Becker, KG
    Simon, RM
    Bailey-Wilson, JE
    Freidlin, B
    Biddison, WE
    McFarland, HF
    Trent, JM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (17) : 9979 - 9984
  • [2] Bodmer JG, 1999, HUM IMMUNOL, V60, P361
  • [3] A genome screen for multiple sclerosis in Italian families
    Broadley, S
    Sawcer, S
    D'Alfonso, S
    Hensiek, A
    Coraddu, F
    Gray, J
    Roxburgh, R
    Clayton, D
    Buttinelli, C
    Quattrone, A
    Trojano, M
    Massacesi, L
    Compston, A
    [J]. GENES AND IMMUNITY, 2001, 2 (04) : 205 - 210
  • [4] Multiple sclerosis in Oslo, Norway: prevalence on 1 January 1995 and incidence over a 25-year period
    Celius, EG
    Vandvik, B
    [J]. EUROPEAN JOURNAL OF NEUROLOGY, 2001, 8 (05) : 463 - 469
  • [5] A genome screen for multiple sclerosis in Sardinian multiplex families
    Coraddu, F
    Sawcer, S
    D'Alfonso, S
    Lai, M
    Hensiek, A
    Solla, E
    Broadley, S
    Mancosu, C
    Pugliatti, M
    Marrosu, MG
    Compston, A
    [J]. EUROPEAN JOURNAL OF HUMAN GENETICS, 2001, 9 (08) : 621 - 626
  • [6] A GENOME-WIDE SEARCH FOR HUMAN TYPE-1 DIABETES SUSCEPTIBILITY GENES
    DAVIES, JL
    KAWAGUCHI, Y
    BENNETT, ST
    COPEMAN, JB
    CORDELL, HJ
    PRITCHARD, LE
    REED, PW
    GOUGH, SCL
    JENKINS, SC
    PALMER, SM
    BALFOUR, KM
    ROWE, BR
    FARRALL, M
    BARNETT, AH
    BAIN, SC
    TODD, JA
    [J]. NATURE, 1994, 371 (6493) : 130 - 136
  • [7] Delepine M, 1997, AM J HUM GENET, V60, P174
  • [8] Ebers GC, 2000, ANN NEUROL, V48, P927, DOI 10.1002/1531-8249(200012)48:6<927::AID-ANA14>3.3.CO
  • [9] 2-6
  • [10] A full genome search in multiple sclerosis
    Ebers, GC
    Kukay, K
    Bulman, DE
    Sadovnick, AD
    Rice, G
    Anderson, C
    Armstrong, H
    Cousin, K
    Bell, RB
    Hader, W
    Paty, DW
    Hashimoto, S
    Oger, J
    Duquette, P
    Warren, S
    Gray, T
    OConnor, P
    Nath, A
    Auty, A
    Metz, L
    Francis, G
    Paulseth, JE
    Murray, TJ
    PrysePhillips, W
    Nelson, R
    Freedman, M
    Brunet, D
    Bouchard, JP
    Hinds, D
    Risch, N
    [J]. NATURE GENETICS, 1996, 13 (04) : 472 - 476