The different approaches to the genetic analysis of autoimmune thyroid disease

被引:24
作者
Allahabadia, A
Gough, SCL [1 ]
机构
[1] Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
[2] Univ Birmingham, Queen Elizabeth Hosp, Birmingham B15 2TH, W Midlands, England
基金
英国惠康基金;
关键词
D O I
10.1677/joe.0.1630007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Graves' disease and Hashimoto's thyroiditis are organ-specific autoimmune disorders of multifactorial aetiology with a polygenic mode of inheritance. Familial clustering and twin studies provide evidence for a genetic predisposition Three main approaches have been used in the search for susceptibility loci: population-based case-control studies, classical linkage analysis, and intrafamilial linkage disequilibrium. Case-control studies are a sensitive method of gene detection and the collection of subjects is resource-efficient. However, they require prior knowledge of a candidate gene and are prone to inconsistent results due to false positives that may arise from population mismatch. Linkage analysis is a powerful tool for detecting 'major' genes that does not require a candidate gene and is, therefore, a means of genome screening. This method, however, has Limited power to detect genes of 'modest' effect, and the collection of sibpairs and multiple family members may be difficult. Intrafamilial linkage disequilibrium analysis is more sensitive than classical linkage analysis, requires only one affected offspring, and eliminates population mismatch. This approach has confirmed Linkage disequilibrium of the HLA region with Graves disease, previously not detected by linkage analysis. Knowledge of a candidate locus is required, however, and this method cannot, therefore, at present be used for genome screening. It is likely that a combination of all three approaches will be: required to identify susceptibility loci for autoimmune thyroid disease.
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页码:7 / 13
页数:7
相关论文
共 41 条
  • [1] Lack of association between polymorphism of the thyrotropin receptor gene and Graves' disease in United Kingdom and Hong Kong Chinese patients: Case control and family-based studies
    Allahabadia, A
    Heward, JM
    Mijovic, C
    Carr-Smith, J
    Daykin, J
    Cockram, C
    Barnett, AH
    Sheppard, MC
    Franklyn, JA
    Gough, SCL
    [J]. THYROID, 1998, 8 (09) : 777 - 780
  • [2] SUSCEPTIBILITY AND RESISTANCE ALLELES OF HUMAN-LEUKOCYTE ANTIGEN (HLA) DQA1 AND HLA DQB1 ARE SHARED IN ENDOCRINE AUTOIMMUNE-DISEASE
    BADENHOOP, K
    WALFISH, PG
    RAU, H
    FISCHER, S
    NICOLAY, A
    BOGNER, U
    SCHLEUSENER, H
    USADEL, KH
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1995, 80 (07) : 2112 - 2117
  • [3] Linkage analysis of candidate genes in autoimmune thyroid disease: 1. Selected immunoregulatory genes
    Barbesino, G
    Tomer, Y
    Concepcion, E
    Davies, TF
    Greenberg, DA
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (05) : 1580 - 1584
  • [4] Association of HLA-DQA1*0501 with Graves' disease in English Caucasian men and women
    Barlow, ABT
    Wheatcroft, N
    Watson, P
    Weetman, AP
    [J]. CLINICAL ENDOCRINOLOGY, 1996, 44 (01) : 73 - 77
  • [5] BARTELS FD, 1941, HEREDITY GRAVES DIS
  • [6] A POLYMORPHIC LOCUS NEAR THE HUMAN INSULIN GENE IS ASSOCIATED WITH INSULIN-DEPENDENT DIABETES-MELLITUS
    BELL, GI
    HORITA, S
    KARAM, JH
    [J]. DIABETES, 1984, 33 (02) : 176 - 183
  • [7] ASSOCIATION OF GRAVES-DISEASE WITH AN ALLELE OF THE INTERLEUKIN-1 RECEPTOR ANTAGONIST GENE
    BLAKEMORE, AIF
    WATSON, PF
    WEETMAN, AP
    DUFF, GW
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1995, 80 (01) : 111 - 115
  • [8] Bluestone JA, 1997, J IMMUNOL, V158, P1989
  • [9] BOEHM BO, 1992, CLIN INVESTIGATOR, V70, P956
  • [10] Brix TH, 1998, CLIN ENDOCRINOL, V48, P397