TY - JOUR
T1 - A new Graves disease-susceptibility locus maps to chromosome 20q11.2
AU - Tomer, Yaron
AU - Barbesino, Giuseppe
AU - Greenberg, David A.
AU - Concepcion, Erlinda
AU - Davies, Terry F.
N1 - Funding Information:
We thank all the AITD families who graciously agreed to participate in the study. This work was supported, in part, by National Institutes of Health grants DK35764, DK45011, and DK52464 (to T.F.D.), DK02498 (to Y.T.), and DK31775, NS27941, and MH48858 (to D.A.G.) and by the David Owen Segal Endowment and the Consorzio Pisa Ricerche, University of Pisa (support to G.B.). Additional members of the International Consortium for the Genetics of Autoimmune Thyroid Disease are Meir Berezin (Tel-Hashomer, Israel), Rhoda Cobin (New York), Luca Chiovato and Aldo Pinchera (Pisa), Sandra McLachlan (Los Angeles), Bernard Rees Smith (Cardiff, Wales), and Fred Clark and Eric Young (Newcastle upon Tyne, United Kingdom). These contributors were not responsible for the content of the present manuscript.
PY - 1998
Y1 - 1998
N2 - The autoimmune thyroid diseases (AITDs) include two related disorders, graves disease (GD) and Hashimoto thyroiditis, in which perturbations of immune regulation result in an immune attack on the thyroid gland. The AITDS are multifactorial and develop in genetically susceptible individuals. However, the genes responsible for this susceptibility remain unknown. Recently, we initiated a whole-genome linkage study of patients with AITD, in order to identify their susceptibility genes. We studied a data set of 53 multiplex, multigenerational AITD families (323 individuals), using highly polymorphic and densely spaced microsatellite markers (intermarker distance <10 cM). Linkage analysis was performed by use of two-point and multipoint parametric methods (classic LOD-score analysis). While studying chromosome 20, we found a locus on chromosome 20q11.2 that was strongly linked to GD. A maximum two-point LOD score of 3.2 was obtained at marker D20S195, assuming a recessive mode of inheritance and a penetrance of .3. The maximum nonparametric LOD score was 2.4 (P = .00043); this score also was obtained at marker D20S195. Multipoint linkage analysis yielded a maximum LOD score of 3.5 for a 6-cM interval between markers D20S195 and D20S107. There was no evidence for heterogeneity in our sample. In our view, these results indicate strong evidence for linkage and suggest the presence of a major GD- susceptibility gene on chromosome 20q11.2.
AB - The autoimmune thyroid diseases (AITDs) include two related disorders, graves disease (GD) and Hashimoto thyroiditis, in which perturbations of immune regulation result in an immune attack on the thyroid gland. The AITDS are multifactorial and develop in genetically susceptible individuals. However, the genes responsible for this susceptibility remain unknown. Recently, we initiated a whole-genome linkage study of patients with AITD, in order to identify their susceptibility genes. We studied a data set of 53 multiplex, multigenerational AITD families (323 individuals), using highly polymorphic and densely spaced microsatellite markers (intermarker distance <10 cM). Linkage analysis was performed by use of two-point and multipoint parametric methods (classic LOD-score analysis). While studying chromosome 20, we found a locus on chromosome 20q11.2 that was strongly linked to GD. A maximum two-point LOD score of 3.2 was obtained at marker D20S195, assuming a recessive mode of inheritance and a penetrance of .3. The maximum nonparametric LOD score was 2.4 (P = .00043); this score also was obtained at marker D20S195. Multipoint linkage analysis yielded a maximum LOD score of 3.5 for a 6-cM interval between markers D20S195 and D20S107. There was no evidence for heterogeneity in our sample. In our view, these results indicate strong evidence for linkage and suggest the presence of a major GD- susceptibility gene on chromosome 20q11.2.
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U2 - 10.1086/302146
DO - 10.1086/302146
M3 - Article
C2 - 9837828
AN - SCOPUS:0032471612
SN - 0002-9297
VL - 63
SP - 1749
EP - 1756
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -