Linkage analysis of candidate genes in autoimmune thyroid disease. III. Detailed analysis of chromosome 14 localizes Graves' disease-1 (GD-1) close to multinodular goiter-1 (MNG-1)

Yaron Tomer, Giuseppe Barbesino, David A. Greenberg, Erlinda Concepcion, Terry F. Davies, Meir Berezin, Rhoda Cobin, Luca Chiovato, Aldo Pinchera, Sandra McLachlan, Bernard Rees Smith, Fred Clark, Eric Young

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Abstract

The autoimmune thyroid diseases [Graves' and Hashimoto's diseases (GD and HT)] develop in genetically susceptible individuals, but the genes responsible for this susceptibility remain unknown. To identify such genes, we have been testing candidate genes and chromosomal regions using highly polymorphic microsatellite markers. We recently reported evidence for the first locus linked to GD (GD-1) on chromosome 14q31 in a small group of families. We have now extended these studies and analyzed 53 multiplex families with GD and/or HT (323 individuals). Chromosome 14 was screened using 16 microsatellite markers spanning the entire chromosome. Three additional markers located inside candidate genes on chromosome 14 were also studied. Microsatellite markers were amplified using fluorescent-labeled primers and separated on an ABI-310 genetic analyzer. The data were analyzed using LIPED software for two-point logarithm of odds (LOD) score analysis and GeneHunter software for multipoint linkage analysis. No linkage of any marker was found to HT or autoimmune thyroid diseases (GD+HT). The previously identified GD-1 locus on 14q31 continued to show evidence of linkage to GD in this much larger set of families. The maximum LOD score was 2.1 obtained for marker D14S81 (0 = 0.01), assuming a recessive mode of inheritance and a penetrance of 0.3. Multipoint analysis yielded a maximum LOD score of 2.5 between markers D14S81 and D14S1054. There was no evidence for heterogeneity in our sample. These data again suggest the presence of a major Graves' disease susceptibility gene (GD-1) on chromosome 14q31. This locus is close to the recently identified multinodular goiter-1 locus.

Original languageEnglish
Pages (from-to)4321-4327
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number12
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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    Tomer, Y., Barbesino, G., Greenberg, D. A., Concepcion, E., Davies, T. F., Berezin, M., Cobin, R., Chiovato, L., Pinchera, A., McLachlan, S., Rees Smith, B., Clark, F., & Young, E. (1998). Linkage analysis of candidate genes in autoimmune thyroid disease. III. Detailed analysis of chromosome 14 localizes Graves' disease-1 (GD-1) close to multinodular goiter-1 (MNG-1). Journal of Clinical Endocrinology and Metabolism, 83(12), 4321-4327.