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Biomedical subjects

I B Rogozin

Publications and source records attributed to I B Rogozin.

At least 37 records · Page 2Linked to original sources
PubMed2000

Computer prediction of sites associated with various elements of the nuclear matrix.

Attachment regions of the eukaryotic chromosomal DNA to the nuclear scaffold/matrix (S/MARs) participate in various important cellular processes. However, no obvious characteristics common for these nucleotide sequences have been revealed, except that S/MARs are non-coding sites containing putative regulatory elements and binding sites of DNA-topoisomerase II. Heterogeneity among S/MARs can be caused by a variety of biological factors. In this paper, the accuracy of two S/MARs prediction programs, MAR-Finder (Singh, Kramer and Krawetz, 1997) and ChrClass (Glazkov, Rogozin and Glazko, 1998) are compared and it is concluded that both programs can be recommended for analysis of eukaryotic genomes. However, results of their prediction should be interpreted with caution since estimation of prediction accuracy of both programs needs further analysis. Problems of S/MARs prediction are illustrated on several examples of human protein-coding genes, repeated elements and the beta-globin locus from different mammalian species. Results of our analysis suggest that the proportion of missed S/MARs is lower for ChrClass, whereas the proportion of wrong S/MARs is lower for MAR-Finder (a default set of parameters).

Animals↗
PubMed2000

Prediction and phylogenetic analysis of mammalian short interspersed elements (SINEs).

The presence of repetitive elements can create serious problems for sequence analysis, especially in the case of homology searches in nucleotide sequence databases. Repetitive elements should be treated carefully by using special programs and databases. In this paper, various aspects of SINE (short interspersed repetitive element) identification, analysis and evolution are discussed.

Animals↗
PubMed1999

Similarity pattern analysis in mutational distributions.

The validity and applicability of the statistical procedure - similarity pattern analysis (SPAN) - to the study of mutational distributions (MDs) was demonstrated with two sets of data. The first was mutational spectra (MS) for 697 GC to AT transitions produced with eight alkylating agents (AAs) in the lacI gene of Escherichia coli. The second was a recently summarized data on the distributions of 11562 spontaneous, radiation- and chemical-induced forward mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa. They were analyzed as large two-way contingency tables (CTs) where two kinds of profiles were compared: site (or genotypic class) profiles and origin (or mutagen) profiles. To measure similarity (homogeneity) between any pair of profiles, the relevant sufficient statistics, Kastenbaum-Hirotsu squared distance (KHi(2)), was used. Collapsing the similar profiles into distinct internally homogeneous clusters named 'collapsets' revealed their similarity pattern. To facilitate the procedure, the computer program, COLLAPSE, was elaborated. The results of SPAN for the lacI spectra were found comparable with the results of their previous analysis with two multivariate statistical methods, the factor and cluster analyses. In the ad-3 data set, five collapsets were revealed among origin profiles (OPs): (I) ENU = 4NQO = 4HAQO = FANFT = SQ18506; (II) AF-2 = EI = MMS = DEP; (III) ETO = UV; (IV) AHA = PROCARB; and (V) He ions = protons. Moreover, the previous observation that MDs are dose-dependent was confirmed for X-ray-induced MDs. Profiles induced with the low doses of X-rays are similar to that induced with 85Sr, and profiles induced with the medium X-ray doses to those induced with protons and He ions. Evaluated similarities appear to be rather reasonable: mutagens with similar mode of action induce similar MDs. Similarity pattern revealed among genotypic class profiles (GCPs) seems to be also interpretable. When supplemented with descriptive cluster analysis, SPAN appears to be a fruitful methodology in MS analysis.

Chromosome Mapping↗
PubMed1999

Protein-coding regions prediction combining similarity searches and conservative evolutionary properties of protein-coding sequences.

The gene identification procedure in a completely new gene with no good homology with protein sequences can be a very complex task. In order to identify the protein-coding region, a new method, 'SYNCOD', based on the analysis of conservative evolutionary properties of coding regions, has been realized. This program is able to identify and use the coding region homologies of the non-annotated (unknown) protein-coding sequences already present in the nucleotide sequence databases by using the alignment produced by BLASTN. The ratio of number mismatches resulting in synonymous codons to the number of mismatches resulting in non-synonymous codons is estimated for each open reading frame. Monte Carlo simulations are then used to estimate the significance of the ratio deviation from random behavior. The SYNCOD program has been tested on generated random sequences and on different control sets. The high accuracy of predicting protein-coding regions (the correlation coefficient, CC, varies from 0.67 to 0.79) and the high specificity (the portion of wrong exons, WE, varies from 0.06 to 0.07) have proved to be important features of the suggested approach. The SYNCOD program is resident on the ITBA-CNR Web Server and can be used via the Internet (URL: www.itba.mi.cnr.it/webgene).

Algorithms↗
PubMed1999

Characterization of several LINE-1 elements in Microtus kirgisorum.

Several LINE-1s have been isolated and characterized from genomic DNA of the vole, Microtus kirgisorum. Blot hybridization revealed specific restriction patterns of L1 elements in vole genomes. Rehybridization of the genomic blot with a cloned 5'-end fragment revealed two major bands indicating the presence of two different L1 subfamilies. The copy numbers are estimated for different parts of M. kirgisorum L1 elements. Data also demonstrate that most vole L1 elements are truncated at the 5'-end; however, in contrast to mouse, the ORF1 copy number is higher in vole. A difference between the substitution rates of the ORF1 5'-region (approximately 330 nucleotides) and the rest of the L1 coding regions is revealed.

Amino Acid Sequence↗
PubMed1998

The subclass approach for mutational spectrum analysis: application of the SEM algorithm.

Analysis and comparison of mutational spectra represents an important problem in molecular biology. To analyse a mutational spectra we apply an algorithm based on the SEM subclass approach (Simulation, Expectation, Maximization). The algorithm tries to classify the mutational sites according to different mutation probabilities, and each site should belong to one class. Each class is approximated by binomial distribution and thus any real mutational spectrum is regarded as a mixture of binomial distributions. The separation process runs iteratively. Each iteration includes the simulation, maximization and estimation procedures. To evaluate the quality of the classification results, the X2 test is used. The algorithm has been checked on random spectra with preset parameters and on real mutational spectra. As has been shown, 17 out of 19 analysed real mutational spectra can be divided into two or more classes of sites, of which one contains hotspots of mutation. For the G:C-->A:T mutational spectra induced by Sn1 alkylating mutagenes (11 spectra) the classification accuracy was 0.95. To test different site volumes, each Sn1-induced spectrum was divided into the G-->A and C-->T spectra. The classification accuracy for these spectra was 0.96. From the analysis of classification errors it is possible to suggest that at least part of them cannot be ascribed to the faults of the algorithm but are caused by some special features of the mutagenesis itself. The results of the real data are in good relation with existing knowledge. The approach we present is an attempt to formalize the concept of a "mutational hotspot". The program implementing the SEM algorithm is available on the Web server (http:/(/)www.itba.mi.cnr.it/webmutation).

Algorithms↗
PubMed1998

Multiple antimutagenesis mechanisms affect mutagenic activity and specificity of the base analog 6-N-hydroxylaminopurine in bacteria and yeast.

Base analog 6-N-hydroxylaminopurine is a potent mutagen in variety of prokaryotic and eukaryotic organisms. In the review, we discuss recent results of the studies of HAP mutagenic activity, genetic control and specificity in bacteria and yeast with the emphasis to the mechanisms protecting living cells from mutagenic and toxic effects of this base analog.

Adenine↗
PubMed1998

A novel subfamily of LINE-derived elements in mice.

Hybrid sequences have been described previously that consist of a 5' region homologous to ORF2 of LINEs and a 3' end that shares homology with a sequence located in the first intron of Cepsilon immunoglobulin. The present investigation has revealed 14 new sequences from seven murine species, that show high homology to those observed earlier. Database search has found several new homologous hybrid sequences including one located in the mouse T-cell receptor (Tcra) locus. Several interesting features of this sequence include identical 15-bp flanking short direct repeats as well as poly-A signal and A-rich sequence at the 3' end. We have classified this set of sequences as LINE-derived elements (LDEs), which constitute a newly observed subfamily. Comparative analysis of these sequences suggests that a single recombination event was responsible for the production of an LDE progenitor. The phylogenetic tree shows a number of elements that pre-existed in the common ancestor of murine species and displays different evolutionary rates. The time of LDE origin is estimated at approximately 10-15 MYA.

Animals↗
PubMed1998

Repetitive DNA sequences in the common vole: cloning, characterization and chromosome localization of two novel complex repeats MS3 and MS4 from the genome of the East European vole Microtus rossiaemeridionalis.

We have characterized two novel, complex, heterochromatic repeat sequences, MS3 and MS4, isolated from Microtus rossiaemeridionalis genomic DNA. Sequence analysis indicates that both repeats consist of unique sequences interrupted by repeat elements of different origin and can be classified as long complex repeat units (LCRUs). A unique feature of both repeat units is the presence of short interspersed repeat elements (SINEs), which are usually characteristic of the euchromatic part of the genome. Comparative analysis revealed no significant stretches of homology in the nucleotide sequences between the two repeats, suggesting that the repeats originated independently during the course of vole genome evolution. Fluorescence in situ hybridization analysis demonstrates that MS3 and MS4 occupy distinct domains in the heterochromatic regions of the sex chromosomes in M. transcaspicus and M. arvalis but collocalize in M. rossiaemeridionalis and M. kirgisorum heterochromatic blocks. The localization pattern of the repeats on the vole chromosomes confirms the independent origin of the two repeats and suggests that expansion of the heterochromatic blocks has occurred subsequent to speciation.

Animals↗
PubMed1997

Identification of a U7snRNA homologue mapping to the human Xq27.1 region, between the DXS1232 and DXS119 loci.

To contribute to the identification and analysis of novel genes, we undertook the study of a cosmid clone in the Xq27 region of human DNA. The cloned fragment was previously observed to have a high number of evolutionarily conserved sequences. In this genomic stretch of DNA we have identified sequence homologous to the U7 RNA gene including its potential regulatory elements. This paper describes the genomic organisation of this gene and its mapping to the Xq27.1 genomic sub-interval between the DXS1232 and DXS119 loci.

Animals↗
PubMed1997

Analysis of donor splice sites in different eukaryotic organisms.

We present here a new algorithm for functional site analysis. It is based on four main assumptions: each variation of nucleotide composition makes a different contribution to the overall binding free energy of interaction between a functional site and another molecule; nonfunctioning site-like regions (pseudosites) are absent or rare in genomes; there may be errors in the sample of sites; and nucleotides of different site positions are considered to be mutually dependent. In this algorithm, the site set is divided into subsets, each described by a certain consensus. Donor splice sites of the human protein-coding genes were analyzed. Comparing the results with other methods of donor splice site prediction has demonstrated a more accurate prediction of consensus sequences AG/GU(A,G), G/GUnAG, /GU(A,G)AG, /GU(A,G)nGU, and G/GUA than is achieved by weight matrix and consensus (A,C)AG/GU(A,G)AGU with mismatches. The probability of the first type error, E1, for the obtained consensus set was about 0.05, and the probability of the second type error, E2, was 0.15. The analysis demonstrated that accuracy of the functional site prediction could be improved if one takes into account correlations between the site positions. The accuracy of prediction by using human consensus sequences was tested on sequences from different organisms. Some differences in consensus sequences for the plant Arabidopsis sp., the invertebrate Caenorhabditis sp., and the fungus Aspergillus sp. were revealed. For the yeast Saccharomyces sp. only one conservative consensus, /GUA(U,A,C)G(U,A,C), was revealed (E1 = 0.03, E2 = 0.03). Yeast is a very interesting model to use for analysis of molecular mechanisms of splicing.

Algorithms↗
PubMed1997

Sequence and gene content in 35 kb genomic clone mapping in the human Xq27.1 region.

This paper presents detailed analysis of the entire sequence of a cosmid clone, 26H7, containing 35 kb of human DNA. This cosmid resides on the q27.1 region of the human X chromosome between, DXS1232 and DXS119 loci. Novel potential small exons were detected for which conventional gene identification strategies (Northern blot analysis and extensive cDNA library screening) proved to be inefficient. Of the standard repetitive elements we found: 8 Alu's making up 6.2% of the sequence; 10 MIR segments (4.1%); 5 LINE1 elements (4.8%), 3 MIR2 (1.0%); 2 MLT (2.9%), and 1 MSTA (0.7%) representing about 20% of the total sequence. The overall GC content was rather low, only 42% and no CpG island was detected using rare restriction enzymes. However, a CpG-rich region was identified. Computer aided analysis of the sequence inferred the presence of three possible genes: one of them was found to be homologous to the U7 RNA family elements; a second is reported in this paper, however at the moment no significant homology has been found in the data bank. The third predicted gene has not as yet been found to be detectable by RT-PCR. We also report in this paper the identification of X-chromosome specific repeated sequences.

Amino Acid Sequence↗
PubMed1996

Somatic hypermutagenesis in immunoglobulin genes. III. Somatic mutations in the chicken light chain locus.

We report a new approach based on the Monte Carlo method, to analyze gene conversion. With this, we have examined 235 somatic mutations in the chicken Vlambda gene and found that about 75% of somatic mutations significantly correlated with donor sequences in 25 pseudo Vlambda genes (set C) versus about 25% that did not (set N). The RGYW and TAA consensus sequences of mutational hotspots were earlier revealed in mammalian V genes. Analysis for correlation between somatic mutations in the Vlambda gene and the consensus sequences showed that the somatic mutations of set N were correlating with the consensus sequences (P(W < Wrandom) < 0.01) and the somatic mutations of set C were not. Based on further statistical analysis, we suggest that there must be at least two mechanisms responsible for somatic hypermutagenesis in the Vlambda gene: gene conversion and another, which accounts for the elevated frequencies of somatic mutations at the RGYW and TAA consensus sequences.

Amino Acid Sequence↗
PubMed1996

Organization and chromosomal localization of a B1-like containing repeat of Microtus subarvalis.

A repetitive DNA sequence, MS2, was isolated from EcoRI-digested genomic DNA of the vole, Microtus subarvalis. The fragment was cloned and sequenced. Sequence analysis of this 1194-bp fragment revealed a 156-bp region demonstrating a 55% homology with the mouse B1 repeat. The remaining MS2 sequence shows no significant homology with other known GenBank sequences. The results of in situ hybridization of MS2 on vole metaphase chromosomes indicate the fragment is confined to heterochromatin blocks of the sex chromosomes in all but one species (M. arvalis). Distribution of MS2 sequences provides evidence for heterogeneity of the giant heterochromatin blocks of the XY Chromosomes (Chrs) in voles, for the unique cluster-like localization of MS2 within these blocks.

Amino Acid Sequence↗
PubMed1996

Gene structure prediction using information on homologous protein sequence.

In this paper a new approach for the prediction of protein coding gene structures is described. The principal scheme of prediction is as follows: first, the exons with the best potential are predicted in a sequence with unknown functions and a list of potential amino acid fragments coded by these exons is formed. Second, testing the homology between each amino acid fragment from the list and proteins from the SWISS-PROT database of amino acid sequences. One protein with the best homology is chosen out of all the homologous sequences. Third, reconstruction of the exon-intron structure, basing it on its homology with the chosen protein sequences. The method was tested on an independent control set (20 genes). The results were as follows: 21% of real exons were lost and 3% of non-real exons were found. This system can be used to refine the results of gene prediction systems, especially if highly homologous proteins are found in the amino acid sequence database.

Algorithms↗
PubMed1995

Subclass approach for mutational spectrum analysis.

Analysis and comparison of mutational spectra represents a burning question in molecular biology. We report an algorithm based upon the SEM subclass approach (SEM--stochastique, estimations, maximizations). Any real mutational spectrum is regarded as a mixture of standard binomial distributions. The separation procedure is run by rounds. Each iteration includes simulation, maximization and estimation. The algorithm has been checked on random spectra with the preset parameters and on real mutational spectra. As has been shown, any real mutational spectrum can be represented as a mixture of two and more binomial distributions, of which one contains hotspots of mutation.

Algorithms↗