Identification and characterization of new variants of three associated SNPs and a microsatellite in the TSH receptor gene which are useful for genetic studies

Mol Cell Probes. 2008 Oct-Dec;22(5-6):281-6. doi: 10.1016/j.mcp.2008.06.003. Epub 2008 Jul 4.

Abstract

The purpose of the present work was to characterize g.IVS5-69C>T, g.IVS6+13C>T and c.561C>T SNPs and the [CT](n) microsatellite in the TSHR gene for genetic analysis. Exons 6 and 7 of the TSHR gene, including the flanking intronic sequences, were screened for the presence of g.IVS5-69C>T, g.IVS6+13C>T and c.561C>T SNPs by SSCP. We found genetic association between the three SNPs and a total of three different haplotypes were observed. Two were homozygous blocks, g.IVS5-69T/g.IVS6+13G/c.561C (Haplotype TGC, 3.3%) and g.IVS5-69C/g.IVS6+13A/c.561T (Haplotype CAT, 75%). Every individual who was heterozygous for g.IVS5-69C>T was equally heterozygous for g.IVS6+13A>G and c.561T>C (Haplotype CAT/TGC, 21.7%). The [CT](n) microsatellite, localized in intron 7 of the TSHR gene was amplified by PCR and the labeled products were separated in a polyacrylamide denaturing sequencing gel. Three variable numbers of CT motif were identified, two previously reported ([CT](6) and [CT](8)) and one previously unreported ([CT](9)). The construction and expression of the hybrid minigenes using pSPL3 and alpha-globin-fibronectin EDB (pTB) vectors showed that the [CT](n) microsatellite itself does not interfere with exon 8 definition and processing in vitro. In conclusion, g.IVS5-69C>T/g.IVS6+13C>T/c.561C>T haplotypes and [CT](n) microsatellite are informative polymorphic markers and can be used in linkage studies in families with germ line TSHR mutations or autoimmunity thyroid diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Exons
  • Haplotypes
  • Humans
  • Microsatellite Repeats*
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide*
  • Receptors, Thyrotropin / genetics*
  • Sequence Analysis, DNA

Substances

  • Receptors, Thyrotropin