Polymorphisms of heat shock factor‐1: Genetic diversity in an evolutionarily conserved, multifunctional regulator gene

Abstract

In the present study we analyzed heat shock factor‐1 (HSF‐1) for SNPs by mining the NCBI dbSNP database and directly sequencing the 13 HSF‐1 exons (2152 nt mRNA sequence) from 60 anonymous genomic DNA samples representing 30 Caucasians and 30 African Americans and comparing these with a reference human HSF‐1 sequence (NT_037704).ResultsMining the dbSNP database revealed 6 SNPs (3 in the 3′UTR and 3 in the coding sequence). One of the coding SNPs causes a proline‐to‐threonine missense at amino acid 365 adjacent to LZ3 and one causes a frame‐shift replacement of the 26‐amino acid C‐terminal transactivation domain. Direct sequencing confirmed the P365T SNP, identified a second novel nonsynonymous SNP (L25I) located in the DNA binding domain, 2 novel 5′UTR and 2 novel 3′UTR SNPs. Four of the five 3′UTR SNPs alter predicted miRNA target sequences (MicroSNiPer) and both 5′UTR SNPs alter predicted 5′UTR secondary structure (RNAFOLD).ConclusionsWe have identified several SNPs in both the coding and untranslated regions that are likely to alter HSF‐1 function and expression level, respectively. The functional consequences of these SNPs will be analyzed by overexpressing in MEFs from HSF‐1‐null mice.