Mining Treasures from 'Junk DNA'

Nowak, Rachel

doi:10.1126/science.7508142

Cited by 149 publications

(58 citation statements)

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“…Their mutation is considered to be a bystander event in the general instability caused by defective mismatch repair (Ionov et al, 1993). There is increasing evidence however to suggest that UTR regions are rich in sequence elements that are essential for gene expression (Nowak, 1994) and some of these are known to contain microsatellites. It is conceivable therefore that deletions in some UTR repeat sequences may have functional consequences in MSI-H tumors.…”

Section: Discussionmentioning

confidence: 99%

Conservation of mononucleotide repeats within 3′ and 5′ untranslated regions and their instability in MSI-H colorectal cancer

et al. 2001

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Section: Discussionmentioning

confidence: 99%

Conservation of mononucleotide repeats within 3′ and 5′ untranslated regions and their instability in MSI-H colorectal cancer

et al. 2001

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“…2,5,[7][8][9][10][11]16,21,30 The core assumption in phylogenetic footprinting is that significant control mechanisms in an organism are evolutionarily conserved. Therefore, by utilizing the genomes of multiple related organisms, one should be able to identify conserved regulatory regions within the DNA.…”

Section: Introductionmentioning

confidence: 99%

Context Specific Transcription Factor Prediction

et al. 2007

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Abstract-One of the goals of systems biology is the identification of regulatory mechanisms that govern an organism's response to external stimuli. Transcription factors have been hypothesized as a major contributor to an organism's response to various outside stimuli, and a great deal of work has been done to predict the set of transcription factors which regulate a given gene. Most of the current methods seek to identify possible binding sites from genomic sequence. Initial attempts at predicting transcription factors from genomic sequences suffered from the problem of false positives. Making the problem more difficult, it has also been shown that while predicted binding sites might be false positives, they can be shown to bind to their corresponding sequences in vitro. One method for rectifying this is through the use of phylogenetic analysis in which only regions which show high evolutionary conservation are analyzed. However such an approach may be too stringent because of the level of degeneracy shown in transcription factor binding site position weight matrices. Due to the degeneracy, there may be only a few bases that need to be conserved across species. Therefore, while a sequence may not show a high level of evolutionary conservation, these sequences may still show high affinity for the same transcription factor. In predicting transcription factor binding we explore the notion that ''Coexpression implies co-regulation'' [Allocco et al. BMC Bioinformatics 5:18, 2004]. With multiple genes requiring similar transcription factors binding sites, there exists a basis for eliminating false positives. This method allows for the selection of transcription factors binding sites that are active under a given experimental paradigm, thereby allowing us to indirectly incorporate the effects of chromosome and recognition site presentation upon transcription factor binding prediction. Rather than having to rationalize that a few transcription factors binding sites are over-represented in a cluster of genes, one can show that a few transcription factors are active in the cluster of genes that have been grouped together. Although the method focuses on predicting experiment-specific transcription factor binding sites, it is possible that if such a methodology were used in an iterative process where different experiments were analyzed, one could obtain a comprehensive set of transcription factors binding sites which regulate the various dynamic responses shown by biological systems under a variety of conditions hence building a more comprehensive model of transcriptional regulation.

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“…The 5 0 and 3 0 UTRs are involved in various biological processes, such as post-transcriptional regulatory pathways, stability and translational efficiency (Sonenberg 1994;Nowak 1994 (Pesole et al 2002). The UTRsite has the data collected from UTRdb and also is continuously enriched with new functional patterns.…”

Section: Functional Snps In Utr Found By the Utrscanmentioning

confidence: 99%

In silico investigations on functional and haplotype tag SNPs associated with congenital long QT syndromes (LQTSs)

Sudandiradoss

Sethumadhavan

2008

HUGO J

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Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases. It is still a major challenge to identify the functional SNPs in disease-related genes. In this review, the genetic variation that can alter the expression and the function of the genes, namely KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2, with the potential role for the development of congenital long QT syndrome (LQTS) was analyzed. Of the total of 3,309 SNPs in all five genes, 27 non-synonymous SNPs (nsSNPs) in the coding region and 44 SNPs in the 5 0 and 3 0 un-translated regions (UTR) were identified as functionally significant. SIFT and PolyPhen programs were used to analyze the nsSNPs and FastSNP; UTR scan programs were used to compute SNPs in the 5 0 and 3 0 untranslated regions. Of the five selected genes, KCNQ1 has the highest number of 26 haplotype blocks and 6 tag SNPs with a complete linkage disequilibrium value. The gene SCN5A has ten haplotype blocks and four tag SNPs. Both KCNE1 and KCNE2 genes have only one haplotype block and four tag SNPs. Four haplotype blocks and two tag SNPs were obtained for KCNH2 gene. Also, this review reports the copy number variations (CNVs), expressed sequence tags (ESTs) and genome survey sequences (GSS) of the selected genes. These computational methods are in good agreement with experimental works reported earlier concerning LQTS.

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Mining Treasures from 'Junk DNA'

Cited by 149 publications

References 1 publication

Conservation of mononucleotide repeats within 3′ and 5′ untranslated regions and their instability in MSI-H colorectal cancer

Conservation of mononucleotide repeats within 3′ and 5′ untranslated regions and their instability in MSI-H colorectal cancer

Context Specific Transcription Factor Prediction

In silico investigations on functional and haplotype tag SNPs associated with congenital long QT syndromes (LQTSs)

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