Search results for: genomes.
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 20

Search results for: genomes.

20 Intuition Operator: Providing Genomes with Reason

Authors: Grigorios N. Beligiannis, Georgios A. Tsirogiannis, Panayotis E. Pintelas

Abstract:

In this contribution, the use of a new genetic operator is proposed. The main advantage of using this operator is that it is able to assist the evolution procedure to converge faster towards the optimal solution of a problem. This new genetic operator is called ''intuition'' operator. Generally speaking, one can claim that this operator is a way to include any heuristic or any other local knowledge, concerning the problem, that cannot be embedded in the fitness function. Simulation results show that the use of this operator increases significantly the performance of the classic Genetic Algorithm by increasing the convergence speed of its population.

Keywords: Genetic algorithms, intuition operator, reasonable genomes, complex search space, nonlinear fitness functions

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19 SeqWord Gene Island Sniffer: a Program to Study the Lateral Genetic Exchange among Bacteria

Authors: Bezuidt O., Lima-Mendez G., Reva O. N.

Abstract:

SeqWord Gene Island Sniffer, a new program for the identification of mobile genetic elements in sequences of bacterial chromosomes is presented. This program is based on the analysis of oligonucleotide usage variations in DNA sequences. 3,518 mobile genetic elements were identified in 637 bacterial genomes and further analyzed by sequence similarity and the functionality of encoded proteins. The results of this study are stored in an open database http://anjie.bi.up.ac.za/geidb/geidbhome. php). The developed computer program and the database provide the information valuable for further investigation of the distribution of mobile genetic elements and virulence factors among bacteria. The program is available for download at www.bi.up.ac.za/SeqWord/sniffer/index.html.

Keywords: mobile genetic elements, virulence, bacterial genomes

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18 MIM: A Species Independent Approach for Classifying Coding and Non-Coding DNA Sequences in Bacterial and Archaeal Genomes

Authors: Achraf El Allali, John R. Rose

Abstract:

A number of competing methodologies have been developed to identify genes and classify DNA sequences into coding and non-coding sequences. This classification process is fundamental in gene finding and gene annotation tools and is one of the most challenging tasks in bioinformatics and computational biology. An information theory measure based on mutual information has shown good accuracy in classifying DNA sequences into coding and noncoding. In this paper we describe a species independent iterative approach that distinguishes coding from non-coding sequences using the mutual information measure (MIM). A set of sixty prokaryotes is used to extract universal training data. To facilitate comparisons with the published results of other researchers, a test set of 51 bacterial and archaeal genomes was used to evaluate MIM. These results demonstrate that MIM produces superior results while remaining species independent.

Keywords: Coding Non-coding Classification, Entropy, GeneRecognition, Mutual Information.

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17 On Reversal and Transposition Medians

Authors: Martin Bader

Abstract:

During the last years, the genomes of more and more species have been sequenced, providing data for phylogenetic recon- struction based on genome rearrangement measures. A main task in all phylogenetic reconstruction algorithms is to solve the median of three problem. Although this problem is NP-hard even for the sim- plest distance measures, there are exact algorithms for the breakpoint median and the reversal median that are fast enough for practical use. In this paper, this approach is extended to the transposition median as well as to the weighted reversal and transposition median. Although there is no exact polynomial algorithm known even for the pairwise distances, we will show that it is in most cases possible to solve these problems exactly within reasonable time by using a branch and bound algorithm.

Keywords: Comparative genomics, genome rearrangements, me-dian, reversals, transpositions.

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16 From Primer Generation to Chromosome Identification: A Primer Generation Genotyping Method for Bacterial Identification and Typing

Authors: Wisam H. Benamer, Ehab A. Elfallah, Mohamed A. Elshaari, Farag A. Elshaari

Abstract:

A challenge for laboratories is to provide bacterial identification and antibiotic sensitivity results within a short time. Hence, advancement in the required technology is desirable to improve timing, accuracy and quality. Even with the current advances in methods used for both phenotypic and genotypic identification of bacteria the need is there to develop method(s) that enhance the outcome of bacteriology laboratories in accuracy and time. The hypothesis introduced here is based on the assumption that the chromosome of any bacteria contains unique sequences that can be used for its identification and typing. The outcome of a pilot study designed to test this hypothesis is reported in this manuscript. Methods: The complete chromosome sequences of several bacterial species were downloaded to use as search targets for unique sequences. Visual basic and SQL server (2014) were used to generate a complete set of 18-base long primers, a process started with reverse translation of randomly chosen 6 amino acids to limit the number of the generated primers. In addition, the software used to scan the downloaded chromosomes using the generated primers for similarities was designed, and the resulting hits were classified according to the number of similar chromosomal sequences, i.e., unique or otherwise. Results: All primers that had identical/similar sequences in the selected genome sequence(s) were classified according to the number of hits in the chromosomes search. Those that were identical to a single site on a single bacterial chromosome were referred to as unique. On the other hand, most generated primers sequences were identical to multiple sites on a single or multiple chromosomes. Following scanning, the generated primers were classified based on ability to differentiate between medically important bacterial and the initial results looks promising. Conclusion: A simple strategy that started by generating primers was introduced; the primers were used to screen bacterial genomes for match. Primer(s) that were uniquely identical to specific DNA sequence on a specific bacterial chromosome were selected. The identified unique sequence can be used in different molecular diagnostic techniques, possibly to identify bacteria. In addition, a single primer that can identify multiple sites in a single chromosome can be exploited for region or genome identification. Although genomes sequences draft of isolates of organism DNA enable high throughput primer design using alignment strategy, and this enhances diagnostic performance in comparison to traditional molecular assays. In this method the generated primers can be used to identify an organism before the draft sequence is completed. In addition, the generated primers can be used to build a bank for easy access of the primers that can be used to identify bacteria.

Keywords: Bacteria chromosome, bacterial identification, sequence, primer generation.

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15 Error-Robust Nature of Genome Profiling Applied for Clustering of Species Demonstrated by Computer Simulation

Authors: Shamim Ahmed Koichi Nishigaki

Abstract:

Genome profiling (GP), a genotype based technology, which exploits random PCR and temperature gradient gel electrophoresis, has been successful in identification/classification of organisms. In this technology, spiddos (Species identification dots) and PaSS (Pattern similarity score) were employed for measuring the closeness (or distance) between genomes. Based on the closeness (PaSS), we can buildup phylogenetic trees of the organisms. We noticed that the topology of the tree is rather robust against the experimental fluctuation conveyed by spiddos. This fact was confirmed quantitatively in this study by computer-simulation, providing the limit of the reliability of this highly powerful methodology. As a result, we could demonstrate the effectiveness of the GP approach for identification/classification of organisms.

Keywords: Fluctuation, Genome profiling (GP), Pattern similarity score (PaSS), Robustness, Spiddos-shift.

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14 Identification of PIP Aquaporin Genes from Wheat

Authors: Sh. A. Yousif, M. Bhave

Abstract:

There is strong evidence that water channel proteins 'aquaporins (AQPs)' are central components in plant-water relations as well as a number of other physiological parameters. We had previously reported the isolation of 24 plasma membrane intrinsic protein (PIP) type AQPs. However, the gene numbers in rice and the polyploid nature of bread wheat indicated a high probability of further genes in the latter. The present work focused on identification of further AQP isoforms in bread wheat. With the use of altered primer design, we identified five genes homologous, designated PIP1;5b, PIP2;9b, TaPIP2;2, TaPIP2;2a, TaPIP2;2b. Sequence alignments indicate PIP1;5b, PIP2;9b are likely to be homeologues of two previously reported genes while the other three are new genes and could be homeologs of each other. The results indicate further AQP diversity in wheat and the sequence data will enable physical mapping of these genes to identify their genomes as well as genetic to determine their association with any quantitative trait loci (QTLs) associated with plant-water relation such as salinity or drought tolerance.

Keywords: Aquaporins, homeologues, PIP, wheat

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13 Evolutionary Distance in the Yeast Genome

Authors: Somayyeh Azizi, Saeed Kaboli, Atsushi Yagi

Abstract:

Whole genome duplication (WGD) increased the number of yeast Saccharomyces cerevisiae chromosomes from 8 to 16. In spite of retention the number of chromosomes in the genome of this organism after WGD to date, chromosomal rearrangement events have caused an evolutionary distance between current genome and its ancestor. Studies under evolutionary-based approaches on eukaryotic genomes have shown that the rearrangement distance is an approximable problem. In the case of S. cerevisiae, we describe that rearrangement distance is accessible by using dedoubled adjacency graph drawn for 55 large paired chromosomal regions originated from WGD. Then, we provide a program extracted from a C program database to draw a dedoubled genome adjacency graph for S. cerevisiae. From a bioinformatical perspective, using the duplicated blocks of current genome in S. cerevisiae, we infer that genomic organization of eukaryotes has the potential to provide valuable detailed information about their ancestrygenome.

Keywords: Whole-genome duplication, Evolution, Double-cutand- join operation, Yeast.

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12 In silico Analysis of Human microRNAs Targeting Influenza a Viruses (subtype H1N1, H5N1 and H3N2)

Authors: Kritsada Khongnomnan, Wittaya Poomipak, Yong Poovorawan, Sunchai Payungporn

Abstract:

In this study, three subtypes of influenza A viruses (pH1N1, H5N1 and H3N2) which naturally infected human were analyzed by bioinformatic approaches to find candidate human cellular miRNAs targeting viral genomes. There were 76 miRNAs targeting influenza A viruses. Among these candidates, 70 miRNAs were subtypes specifically targeting each subtype of influenza A virus including 21 miRNAs targeted subtype H1N1, 27 miRNAs targeted subtype H5N1 and 22 miRNAs targeted subtype H3N2. The remaining 6 miRNAs target on multiple subtypes of influenza A viruses. Uniquely, hsa-miR-3145 is the only one candidate miRNA targeting PB1 gene of all three subtypes. Obviously, most of the candidate miRNAs are targeting on polymerase complex genes (PB2, PB1 and PA) of influenza A viruses. This study predicted potential human miRNAs targeting on different subtypes of influenza A viruses which might be useful for inhibition of viral replication and for better understanding of the interaction between virus and host cell.

Keywords: Human miRNAs, Influenza A viruses, H1N1, H5N1, H3N2

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11 Construction of cDNALibrary and EST Analysis of Tenebriomolitorlarvae

Authors: JiEun Jeong, Se-Won Kang, Hee-Ju Hwang, Sung-Hwa Chae, Sang-Haeng Choi, Hong-SeogPark, YeonSoo Han, Bok-Reul Lee, Dae-Hyun Seog, Yong Seok Lee

Abstract:

Tofurther advance research on immune-related genes from T. molitor, we constructed acDNA library and analyzed expressed sequence taq (EST) sequences from 1,056 clones. After removing vector sequence and quality checkingthrough thePhred program (trim_alt 0.05 (P-score>20), 1039 sequences were generated. The average length of insert was 792 bp. In addition, we identified 162 clusters, 167 contigs and 391 contigs after clustering and assembling process using a TGICL package. EST sequences were searchedagainst NCBI nr database by local BLAST (blastx, EKeywords: EST, Innate immunity, Tenebriomolitor

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10 Unsupervised Classification of DNA Barcodes Species Using Multi-Library Wavelet Networks

Authors: Abdesselem Dakhli, Wajdi Bellil, Chokri Ben Amar

Abstract:

DNA Barcode provides good sources of needed information to classify living species. The classification problem has to be supported with reliable methods and algorithms. To analyze species regions or entire genomes, it becomes necessary to use the similarity sequence methods. A large set of sequences can be simultaneously compared using Multiple Sequence Alignment which is known to be NP-complete. However, all the used methods are still computationally very expensive and require significant computational infrastructure. Our goal is to build predictive models that are highly accurate and interpretable. In fact, our method permits to avoid the complex problem of form and structure in different classes of organisms. The empirical data and their classification performances are compared with other methods. Evenly, in this study, we present our system which is consisted of three phases. The first one, is called transformation, is composed of three sub steps; Electron-Ion Interaction Pseudopotential (EIIP) for the codification of DNA Barcodes, Fourier Transform and Power Spectrum Signal Processing. Moreover, the second phase step is an approximation; it is empowered by the use of Multi Library Wavelet Neural Networks (MLWNN). Finally, the third one, is called the classification of DNA Barcodes, is realized by applying the algorithm of hierarchical classification.

Keywords: DNA Barcode, Electron-Ion Interaction Pseudopotential, Multi Library Wavelet Neural Networks.

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9 An Advanced Nelder Mead Simplex Method for Clustering of Gene Expression Data

Authors: M. Pandi, K. Premalatha

Abstract:

The DNA microarray technology concurrently monitors the expression levels of thousands of genes during significant biological processes and across the related samples. The better understanding of functional genomics is obtained by extracting the patterns hidden in gene expression data. It is handled by clustering which reveals natural structures and identify interesting patterns in the underlying data. In the proposed work clustering gene expression data is done through an Advanced Nelder Mead (ANM) algorithm. Nelder Mead (NM) method is a method designed for optimization process. In Nelder Mead method, the vertices of a triangle are considered as the solutions. Many operations are performed on this triangle to obtain a better result. In the proposed work, the operations like reflection and expansion is eliminated and a new operation called spread-out is introduced. The spread-out operation will increase the global search area and thus provides a better result on optimization. The spread-out operation will give three points and the best among these three points will be used to replace the worst point. The experiment results are analyzed with optimization benchmark test functions and gene expression benchmark datasets. The results show that ANM outperforms NM in both benchmarks.

Keywords: Spread out, simplex, multi-minima, fitness function, optimization, search area, monocyte, solution, genomes.

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8 BeamGA Median: A Hybrid Heuristic Search Approach

Authors: Ghada Badr, Manar Hosny, Nuha Bintayyash, Eman Albilali, Souad Larabi Marie-Sainte

Abstract:

The median problem is significantly applied to derive the most reasonable rearrangement phylogenetic tree for many species. More specifically, the problem is concerned with finding a permutation that minimizes the sum of distances between itself and a set of three signed permutations. Genomes with equal number of genes but different order can be represented as permutations. In this paper, an algorithm, namely BeamGA median, is proposed that combines a heuristic search approach (local beam) as an initialization step to generate a number of solutions, and then a Genetic Algorithm (GA) is applied in order to refine the solutions, aiming to achieve a better median with the smallest possible reversal distance from the three original permutations. In this approach, any genome rearrangement distance can be applied. In this paper, we use the reversal distance. To the best of our knowledge, the proposed approach was not applied before for solving the median problem. Our approach considers true biological evolution scenario by applying the concept of common intervals during the GA optimization process. This allows us to imitate a true biological behavior and enhance genetic approach time convergence. We were able to handle permutations with a large number of genes, within an acceptable time performance and with same or better accuracy as compared to existing algorithms.

Keywords: Median problem, phylogenetic tree, permutation, genetic algorithm, beam search, genome rearrangement distance.

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7 Antibody Reactivity of Synthetic Peptides Belonging to Proteins Encoded by Genes Located in Mycobacterium tuberculosis-Specific Genomic Regions of Differences

Authors: Abu Salim Mustafa

Abstract:

The comparisons of mycobacterial genomes have identified several Mycobacterium tuberculosis-specific genomic regions that are absent in other mycobacteria and are known as regions of differences. Due to M. tuberculosis-specificity, the peptides encoded by these regions could be useful in the specific diagnosis of tuberculosis. To explore this possibility, overlapping synthetic peptides corresponding to 39 proteins predicted to be encoded by genes present in regions of differences were tested for antibody-reactivity with sera from tuberculosis patients and healthy subjects. The results identified four immunodominant peptides corresponding to four different proteins, with three of the peptides showing significantly stronger antibody reactivity and rate of positivity with sera from tuberculosis patients than healthy subjects. The fourth peptide was recognized equally well by the sera of tuberculosis patients as well as healthy subjects. Predication of antibody epitopes by bioinformatics analyses using ABCpred server predicted multiple linear epitopes in each peptide. Furthermore, peptide sequence analysis for sequence identity using BLAST suggested M. tuberculosis-specificity for the three peptides that had preferential reactivity with sera from tuberculosis patients, but the peptide with equal reactivity with sera of TB patients and healthy subjects showed significant identity with sequences present in nob-tuberculous mycobacteria. The three identified M. tuberculosis-specific immunodominant peptides may be useful in the serological diagnosis of tuberculosis.

Keywords: Genomic regions of differences, Mycobacterium tuberculosis, peptides, serodiagnosis.

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6 Cloning and Functional Characterization of Promoter Elements of the D Hordein Gene from the Barley (Hordeum vulgare L.) by Bioinformatic Tools

Authors: Kobra Nalbandi, Bahram Baghban Kohnehrouz, Khalil Alami Saeed

Abstract:

The low level of foreign genes expression in transgenic plants is a key factor that limits plant genetic engineering. Because of the critical regulatory activity of the promoters on gene transcription, they are studied extensively to improve the efficiency of the plant transgenic system. The strong constitutive promoters, such as CaMV 35S promoter and Ubiqutin 1 maize are usually used in plant biotechnology research. However the expression level of the foreign genes in all tissues is often undesirable. But using a strong seed-specific promoter to limit gene expression in the seed solves such problems. The purpose of this study is to isolate one of the seed specific promoters of Hordeum vulgare. So one of the common varieties of Hordeum vulgare in Iran was selected and their genomes extracted then the D-Hordein promoter amplified using the specific designed primers. Then the amplified fragment of the insert cloned in an appropriate vector and then transformed to E. coli. At last for the final admission of accuracy the cloned fragments sent for sequencing. Sequencing analysis showed that the cloned fragment DHPcontained motifs; like TATA box, CAAT-box, CCGTCC-box, AMYBOX1 and E-box etc., which constituted the seed-specific promoter activity. The results were compared with sequences existing in data banks. D-Hordein promoters of Alger has 99% similarity at 100 % coverage. The results also showed that D-Hordein promoter of barley and HMW promoter of wheat are too similar.

Keywords: Barley, Seed specific promoter, Hordein.

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5 Statistics of Exon Lengths in Animals, Plants, Fungi, and Protists

Authors: Alexander Kaplunovsky, Vladimir Khailenko, Alexander Bolshoy, Shara Atambayeva, AnatoliyIvashchenko

Abstract:

Eukaryotic protein-coding genes are interrupted by spliceosomal introns, which are removed from the RNA transcripts before translation into a protein. The exon-intron structures of different eukaryotic species are quite different from each other, and the evolution of such structures raises many questions. We try to address some of these questions using statistical analysis of whole genomes. We go through all the protein-coding genes in a genome and study correlations between the net length of all the exons in a gene, the number of the exons, and the average length of an exon. We also take average values of these features for each chromosome and study correlations between those averages on the chromosomal level. Our data show universal features of exon-intron structures common to animals, plants, and protists (specifically, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Cryptococcus neoformans, Homo sapiens, Mus musculus, Oryza sativa, and Plasmodium falciparum). We have verified linear correlation between the number of exons in a gene and the length of a protein coded by the gene, while the protein length increases in proportion to the number of exons. On the other hand, the average length of an exon always decreases with the number of exons. Finally, chromosome clustering based on average chromosome properties and parameters of linear regression between the number of exons in a gene and the net length of those exons demonstrates that these average chromosome properties are genome-specific features.

Keywords: Comparative genomics, exon-intron structure, eukaryotic clustering, linear regression.

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4 Evolutionary Origin of the αC Helix in Integrins

Authors: B. Chouhan, A. Denesyuk, J. Heino, M. S. Johnson, K. Denessiouk

Abstract:

Integrins are a large family of multidomain α/β cell signaling receptors. Some integrins contain an additional inserted I domain, whose earliest expression appears to be with the chordates, since they are observed in the urochordates Ciona intestinalis (vase tunicate) and Halocynthia roretzi (sea pineapple), but not in integrins of earlier diverging species. The domain-s presence is viewed as a hallmark of integrins of higher metazoans, however in vertebrates, there are clearly three structurally-different classes: integrins without I domains, and two groups of integrins with I domains but separable by the presence or absence of an additional αC helix. For example, the αI domains in collagen-binding integrins from Osteichthyes (bony fish) and all higher vertebrates contain the specific αC helix, whereas the αI domains in non-collagen binding integrins from vertebrates and the αI domains from earlier diverging urochordate integrins, i.e. tunicates, do not. Unfortunately, within the early chordates, there is an evolutionary gap due to extinctions between the tunicates and cartilaginous fish. This, coupled with a knowledge gap due to the lack of complete genomic data from surviving species, means that the origin of collagen-binding αC-containing αI domains remains unknown. Here, we analyzed two available genomes from Callorhinchus milii (ghost shark/elephant shark; Chondrichthyes – cartilaginous fish) and Petromyzon marinus (sea lamprey; Agnathostomata), and several available Expression Sequence Tags from two Chondrichthyes species: Raja erinacea (little skate) and Squalus acanthias (dogfish shark); and Eptatretus burgeri (inshore hagfish; Agnathostomata), which evolutionary reside between the urochordates and osteichthyes. In P. marinus, we observed several fragments coding for the αC-containing αI domain, allowing us to shed more light on the evolution of the collagen-binding integrins.

Keywords: Integrin αI domain, integrin evolution, collagen binding, structure, αC helix

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3 Identification of Promiscuous Epitopes for Cellular Immune Responses in the Major Antigenic Protein Rv3873 Encoded by Region of Difference 1 of Mycobacterium tuberculosis

Authors: Abu Salim Mustafa

Abstract:

Rv3873 is a relatively large size protein (371 amino acids in length) and its gene is located in the immunodominant genomic region of difference (RD)1 that is present in the genome of Mycobacterium tuberculosis but deleted from the genomes of all the vaccine strains of Bacillus Calmette Guerin (BCG) and most other mycobacteria. However, when tested for cellular immune responses using peripheral blood mononuclear cells from tuberculosis patients and BCG-vaccinated healthy subjects, this protein was found to be a major stimulator of cell mediated immune responses in both groups of subjects. In order to further identify the sequence of immunodominant epitopes and explore their Human Leukocyte Antigen (HLA)-restriction for epitope recognition, 24 peptides (25-mers overlapping with the neighboring peptides by 10 residues) covering the sequence of Rv3873 were synthesized chemically using fluorenylmethyloxycarbonyl chemistry and tested in cell mediated immune responses. The results of these experiments helped in the identification of an immunodominant peptide P9 that was recognized by people expressing varying HLA-DR types. Furthermore, it was also predicted to be a promiscuous binder with multiple epitopes for binding to HLA-DR, HLA-DP and HLA-DQ alleles of HLA-class II molecules that present antigens to T helper cells, and to HLA-class I molecules that present antigens to T cytotoxic cells. In addition, the evaluation of peptide P9 using an immunogenicity predictor server yielded a high score (0.94), which indicated a greater probability of this peptide to elicit a protective cellular immune response. In conclusion, P9, a peptide with multiple epitopes and ability to bind several HLA class I and class II molecules for presentation to cells of the cellular immune response, may be useful as a peptide-based vaccine against tuberculosis.

Keywords: Mycobacterium tuberculosis, Rv3873, peptides, vaccine

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2 Identification of Complex Sense-antisense Gene's Module on 17q11.2 Associated with Breast Cancer Aggressiveness and Patient's Survival

Authors: O. Grinchuk, E. Motakis, V. Kuznetsov

Abstract:

Sense-antisense gene pair (SAGP) is a pair of two oppositely transcribed genes sharing a common region on a chromosome. In the mammalian genomes, SAGPs can be organized in more complex sense-antisense gene architectures (CSAGA) in which at least one gene could share loci with two or more antisense partners. Many dozens of CSAGAs can be found in the human genome. However, CSAGAs have not been systematically identified and characterized in context of their role in human diseases including cancers. In this work we characterize the structural-functional properties of a cluster of 5 genes –TMEM97, IFT20, TNFAIP1, POLDIP2 and TMEM199, termed TNFAIP1 / POLDIP2 module. This cluster is organized as CSAGA in cytoband 17q11.2. Affymetrix U133A&B expression data of two large cohorts (410 atients, in total) of breast cancer patients and patient survival data were used. For the both studied cohorts, we demonstrate (i) strong and reproducible transcriptional co-regulatory patterns of genes of TNFAIP1/POLDIP2 module in breast cancer cell subtypes and (ii) significant associations of TNFAIP1/POLDIP2 CSAGA with amplification of the CSAGA region in breast cancer, (ii) cancer aggressiveness (e.g. genetic grades) and (iv) disease free patient-s survival. Moreover, gene pairs of this module demonstrate strong synergetic effect in the prognosis of time of breast cancer relapse. We suggest that TNFAIP1/ POLDIP2 cluster can be considered as a novel type of structural-functional gene modules in the human genome.

Keywords: Sense-antisense gene pair, complex genome architecture, TMEM97, IFT20, TNFAIP1, POLDIP2, TMEM199, 17q11.2, breast cancer, transcription regulation, survival analysis, prognosis.

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1 Bioinformatic Analysis of Retroelement-Associated Sequences in Human and Mouse Promoters

Authors: Nadezhda M. Usmanova, Nikolai V. Tomilin

Abstract:

Mammalian genomes contain large number of retroelements (SINEs, LINEs and LTRs) which could affect expression of protein coding genes through associated transcription factor binding sites (TFBS). Activity of the retroelement-associated TFBS in many genes is confirmed experimentally but their global functional impact remains unclear. Human SINEs (Alu repeats) and mouse SINEs (B1 and B2 repeats) are known to be clustered in GCrich gene rich genome segments consistent with the view that they can contribute to regulation of gene expression. We have shown earlier that Alu are involved in formation of cis-regulatory modules (clusters of TFBS) in human promoters, and other authors reported that Alu located near promoter CpG islands have an increased frequency of CpG dinucleotides suggesting that these Alu are undermethylated. Human Alu and mouse B1/B2 elements have an internal bipartite promoter for RNA polymerase III containing conserved sequence motif called B-box which can bind basal transcription complex TFIIIC. It has been recently shown that TFIIIC binding to B-box leads to formation of a boundary which limits spread of repressive chromatin modifications in S. pombe. SINEassociated B-boxes may have similar function but conservation of TFIIIC binding sites in SINEs located near mammalian promoters has not been studied earlier. Here we analysed abundance and distribution of retroelements (SINEs, LINEs and LTRs) in annotated sequences of the Database of mammalian transcription start sites (DBTSS). Fractions of SINEs in human and mouse promoters are slightly lower than in all genome but >40% of human and mouse promoters contain Alu or B1/B2 elements within -1000 to +200 bp interval relative to transcription start site (TSS). Most of these SINEs is associated with distal segments of promoters (-1000 to -200 bp relative to TSS) indicating that their insertion at distances >200 bp upstream of TSS is tolerated during evolution. Distribution of SINEs in promoters correlates negatively with the distribution of CpG sequences. Using analysis of abundance of 12-mer motifs from the B1 and Alu consensus sequences in genome and DBTSS it has been confirmed that some subsegments of Alu and B1 elements are poorly conserved which depends in part on the presence of CpG dinucleotides. One of these CpG-containing subsegments in B1 elements overlaps with SINE-associated B-box and it shows better conservation in DBTSS compared to genomic sequences. It has been also studied conservation in DBTSS and genome of the B-box containing segments of old (AluJ, AluS) and young (AluY) Alu repeats and found that CpG sequence of the B-box of old Alu is better conserved in DBTSS than in genome. This indicates that Bbox- associated CpGs in promoters are better protected from methylation and mutation than B-box-associated CpGs in genomic SINEs. These results are consistent with the view that potential TFIIIC binding motifs in SINEs associated with human and mouse promoters may be functionally important. These motifs may protect promoters from repressive histone modifications which spread from adjacent sequences. This can potentially explain well known clustering of SINEs in GC-rich gene rich genome compartments and existence of unmethylated CpG islands.

Keywords: Retroelement, promoter, CpG island, DNAmethylation.

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