title: Allele-specific transcript quantification detects haplotypic variation in the levels of the SDF-1 transcripts.
abstract: It has been suggested that SDF1-G801A, a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the SDF1 gene, is associated with susceptibility to diseases such as AIDS and type-I diabetes. However, experimental studies examining the effect of SDF1-G801A on SDF-1 expression have not supported its functional importance. In this study, to examine whether other polymorphisms have a cis-acting effect on SDF1 expression, we carried out haplotype analyses of the SDF1 gene and the allele-specific transcript quantification utilizing Epstein-Barr virus-transformed lymphoblastoid cell lines with heterozygous genotype for SDF1-G801A. Haplotype-based analyses on the proportion of the allele-specific transcripts revealed the presence of haplotypes associated with a decreased amount of the transcripts. In addition, we observed haplotypic variation in response to dibutyl cyclic AMP and tetradecanoyl phorbol acetate that enhances the levels of SDF-1 transcripts probably through activation of transcription factors. Showing evidence that polymorphisms other than the SDF1-G801A have a cis-acting effect on expression of SDF-1 transcripts, the results of this study contribute to the interpretation of previous disease-association studies and to the selection of SNP markers for future studies. As shown in this study, allele-specific transcript quantification coupled with haplotype analyses can be an effective tool for detecting cis-acting polymorphisms in expressional regulation.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kimura
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishioka
authors.forename: Augustinus
authors.initials: A
authors.lastname: Soemantri
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ishida
mesh_terms: D000483:Alleles; D003994:Bucladesine / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: C515255:CXCL12 protein, human; D002273:Carcinogens; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D012333:RNA, Messenger; D003994:Bucladesine; D013755:Tetradecanoylphorbol Acetate