Investigations into the molecular effects of single nucleotide polymorphism.
OBJECTIVE
DNA sequences are very rich in short repeats and their pattern can be altered by point mutations. We wanted to investigate the effect of single nucleotide polymorphism (SNP) on the pattern of short DNA repeats and its biological consequences.


METHODS
Analysis of the pattern of short DNA repeats of the Thy-1 sequence with and without SNP. Searching for DNA-binding factors in any region of significance.


RESULTS
Comparing the pattern of short repeats in the Thy-1 gene sequences of Turkish patients with ataxia telangiectasia (AT) with the "wild type" sequence from the DNA database, we identified a missing 8-bp repeat element due to an SNP in position 1271 (intron II) in AT-DNA sequences. Only the mutated sequence had the potential for the formation of a stem loop in DNA or pre-mRNA. In super-shift experiments we found that DNA oligomers covering the area of this SNP formed a complex with proteins amongst which we identified the proliferating cell nuclear antigen (PCNA) protein.


CONCLUSIONS
SNPs have the potential to alter DNA or pre-mRNA conformation. Although no SNP-depeding formation of the DNA-protein complex was evident, future investigations could reveal differential molecular mechanisms of cellular regulation.
Lohrer
H D
HD
Radiobiological Institute, Ludwig Maximilians University, Munich, Germany.
Tangen
U
U
D001260:Ataxia Telangiectasia / Q000235:genetics; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D018900:Dinucleotide Repeats / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017422:Sequence Analysis, DNA; D018800:Thy-1 Antigens / Q000235:genetics
D017931:DNA Primers; D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D018800:Thy-1 Antigens