Thirteen single-nucleotide polymorphisms in the human osteopontin gene identified by sequencing of the entire gene in Japanese individuals

Iwasaki, Hiromichi; Shinohara, Yasutomo; Ezura, Yoichi; Ishida, Ryota; Kodaira, Mina; Kajita, Mitsuko; Nakajima, Toshiaki; Shiba, Tadayoshi; Emi, Mitsuru

doi:10.1007/s100380170037

Cited by 22 publications

(17 citation statements)

References 5 publications

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“…1B shows the sequence between Ϫ462 and ϩ3. Three of these SNPs (ϩ245, ϩ954, ϩ1020) were located in the first intron: the first one (ϩ245) was previously described by us, and the two others were already reported in the Japanese population (17). Six novel SNPs were found in the sequence upstream of the transcription start site and also confirmed in a recent Japanese Fig.…”

Section: Snp Identification and Haplotype Reconstructionsupporting

confidence: 61%

“…Several polymorphisms in the human OPN encoding gene have been identified in different populations: some have been reported in the 5Ј flanking region in a Japanese population (22), others in exons and introns and in the 3Ј untranslated region (12,17). Our work was aimed at verifying whether alleles at polymorphic sites in the 5Ј flanking region were able to influence the level of promoter activity and characterizing their ability to bind transcription factors.…”

Section: Discussionmentioning

confidence: 99%

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Polymorphisms in the osteopontin promoter affect its transcriptional activity

Giacopelli

Marciano

Pistorio

et al. 2004

Physiological Genomics

120

133

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.-Understanding the molecular mechanisms that underlie regulation of transcription of the human osteopontin encoding gene (OPN) may help to clarify several processes, such as fibrotic evolution of organ damage, tumorigenesis and metastasis, and immune response, in which OPN overexpression is observed. With the aim to evaluate variants with functional effect on transcription, we have analyzed the promoter region and focused our investigation on three common variants present in the first 500 bp upstream of the transcription start site. Transfection of constructs carrying the four most frequent haplotypes relative to variants at Ϫ66, Ϫ156, and Ϫ443 fused to the luciferase reporter gene in a panel of different cell lines showed that one haplotype conferred a significantly reduced level of reporter gene expression in all tested cell lines. We describe that the Ϫ66 polymorphism modifies the binding affinity for the SP1/SP3 transcription factors, the Ϫ156 polymorphism is included in a yet uncharacterized RUNX2 binding site, and the Ϫ443 polymorphism causes differential binding of an unknown factor. The finding of differential effects of various combination of variants in haplotypes may contribute to explain data of association studies reported in several already published articles. Future association studies using haplotypes instead of single OPN variants will allow to achieve more accurate results referable to differential expression of OPN in several common diseases, in which OPN is considered a candidate susceptibility gene.

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Section: Snp Identification and Haplotype Reconstructionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the osteopontin promoter affect its transcriptional activity

Giacopelli

Marciano

Pistorio

et al. 2004

Physiological Genomics

120

133

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“…As a result of this worldwide intensive effort, more than 2.8 million SNPs have been identified and a high-density map has been constructed in some cases (Iida et al 2001a-d;Iwasaki et al 2001;Saito et al 2001;Osier et al 2001). Although several mapping methods (Table 2), such as single-strand conformational polymorphism (Orita et al 1989), denaturing gradient gel electrophoresis (DGGE), enzymatic mutation detection (Youil et al 1995), microarray or variant detector arrays (Wang et al 1998;Marshall and Hodgson 1998;Ramsay 1998;Dong et al 2001;Qi et al 2001;Yoshino et al 2001), and heteroduplex analysis (Lichten and Fox 1983) are available, so far none of them has supplanted DNA sequencing as the method of choice.…”

Section: Mapping and Characterization Of Snpsmentioning

confidence: 99%

SNP alleles in human disease and evolution

Shastry¹

2002

J Hum Genet

329

176

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information and how to take advantage of this effort. The majority of them believe that one possible benefit of this information is to use it to understand the genetic basis of the most common familial traits, evolutionary processes, and complex and common diseases such as hypertension, diabetes, obesity, and psychiatric disorders. These common diseases are likely to be caused by multiple genes and multiple nongenetic factors (environmental factors), each contributing a modest effect. Their cumulative effect results in the condition or trait. The traditional methods of identifying disease-related genes are not readily applicable to the detection of genes responsible for these multifactorial diseases. The availability of the entire genome sequence, therefore, may speed up the gene-hunting efforts in the near future, but what approaches are to be taken to accomplish this task and what are their limitations?The human genome and the discovery of singlenucleotide polymorphisms (SNPs) as genetic markersIn two randomly selected human genomes, 99.9% of the DNA sequence is identical. The remaining 0.1% is thought to include some differences or variations in the genome between individuals. This variation, called polymorphism, arises because of mutations. The simplest form of these variations is the substitution of one single nucleotide for another (Fig. 1A), termed SNP. SNPs are more common than other types of polymorphisms and occur at a frequency of approximately 1 in 1000 base pairs (Brookes 1999) throughout the genome (promoter region, coding sequences, and intronic sequences). These simple changes in DNA sequence, most of which are probably located in intergenic spacers, are believed to be stable and not deleterious to organisms. SNPs that do not change encoded amino acids are called synonymous and are not subject to natural selection (Kimura 1983, snp.cshl.org). On the other hand, nonsynonymous SNPs alter amino acids and might be subject to natural selection. SNPs can be observed between individuals in a population, may influence promoter activity B.S. Shastry (*) Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA Tel. ϩ1-248-370-3577; Fax ϩ1-248-370-4225 e-mail: Barkur@aol.com Abstract In two randomly selected human genomes, 99.9% of the DNA sequence is identical. The remaining 0.1% of DNA contains sequence variations. The most common type of such variation is called a single-nucleotide polymorphism, or SNP. SNPs are highly abundant, stable, and distributed throughout the genome. These variations are associated with diversity in the population, individuality, susceptibility to diseases, and individual response to medicine. Recently, it has been suggested that SNPs can be used for homogeneity testing and pharmacogenetic studies and to identify and map complex, common diseases such as high blood pressure, diabetes, and heart disease. Consistent with this proposal is the identification of the patterns of SNPs in conditions such as diabetes, schizophrenia, and bloodpressure homeostasis. Alt...

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“…ncbi.nlm.nih.gov/SNP/index.html) on the basis of its location, allele frequencies, and polymorphic characteristics (Table 1). SNP genotyping was performed by cycle resequencing of PCR products (Iwasaki et al 2001). Plasmid construction A 1006-bp fragment of the apoA-II promoter region that was sufficient to promote maximum transcriptional activity (Ribeiro et al 1999) was PCR-amplified from peripheral leukocyte DNAs of individuals homozygous for either the Ϫ265T variant or the Ϫ265C variant.…”

Section: Flow-cytometric Functional Analyses Of the Ldl Receptormentioning

confidence: 99%