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Biomedical subjects

I B Rogozin

Publications and source records attributed to I B Rogozin.

At least 55 records · Page 3Linked to original sources
PubMed1992

Somatic hypermutagenesis in immunoglobulin genes. II. Influence of neighbouring base sequences on mutagenesis.

A new approach for the analysis of hotspots of mutations is described. It is based on the classification of hotspot site sequences. Using this approach, the consensuses RGYW and TAA of hotspot sites were revealed in the V gene. Correlation between somatic mutations and these consensuses is investigated by the statistical weight method in 323 somatic substitutions in 14 V genes. Assuming the absence of any correlation, the probability of observing such data in the sample would be very low (0.0003). These results support the idea that emergence of somatic mutation is significantly influenced by neighbouring base sequences. This idea was also supported by the analysis of 296 somatic mutations in flanking sequences of V genes. It is supposed that this influence is an important feature of somatic hypermutagenesis.

Animals↗
PubMed1992

Molecular organization and evolution of the D17Leh80-like loci in the mouse t complex.

We determined the sequence of Tu80, one of the molecular clones derived from microdissected fragments of Chromosome (Chr) 17. The sequence data demonstrated that Tu80 contains an open reading frame (ORF) of 204 bp. Two sequences within the ORF, one homologous to the LINE1 element and the other to the first intron of the C epsilon gene of mouse immunoglobulin, were observed. A separate sequence, homologous to Tu80, designated as NOV1, was isolated from a genomic library of mouse Chr 17. NOV1 was found to contain an inserted B2 repeat, making it structurally different from Tu80. The sequences of Tu80 and NOV1 were compared with those of LINE1 and the first intron of the C epsilon gene. The results suggest that the ancestor of the Tu80-like sequence might have arisen through recombination between a LINE1 element and the C epsilon gene. It is concluded that Tu80 and NOV1 might have resulted from duplication of an ancestral sequence followed by divergence. The comparative analysis also demonstrated a high degree of conservation of the LINE1-like sequence in Tu80 and NOV1. Based on the structure of human, rat, rabbit, and mouse LINE1 fragments, as well as those of NOV1 and Tu80, a phylogenetic tree was constructed. The available data tend to support the assumption that the ancestor for the Tu80-like sequence might have arisen not later than 27-33 million years ago.

Alleles↗
PubMed1992

[Structure and evolution of the D17LeH80-like locus in the murine t-complex].

The t complex in the proximal part of chromosome 17 is one of the most thoroughly studied regions of the mouse genome. We determined the sequence of Tu80, a molecular clone derived from microdissected fragments of chromosome 17. The sequence data demonstrated that the total length being 324 bp, Tu80 contains an open-reading frame (ORF) of 204 bp. Two fragments were detected within the ORF, one homologous to the LINE1-element, the other to the first intron of the C epsilon gene of mouse immunoglobin. A sequence designated NOV1 was isolated from the genomic library of mouse chromosome 17. NOV1 was found to contain a B2 insert, making in structurally different from Tu80. The sequences of Tu80 and NOV1 were compared with those of LINE1 and the first intron of the C epsilon gene. The results suggested that the ancestor of the Tu80-like sequence might have arisen through illegitimate recombination between the fragments of LINE1 and the C epsilon gene. It is concluded that Tu80 and NOV1 might have resulted from duplication of the ancestral sequence and following divergence. The comparative analysis also demonstrated high degree of conservation of the LINE1 fragments in Tu80 and NOV1, as well as in the LINE1 in a number of mammalian species. Based on the structure of human, rat, rabbit and mouse LINE1 fragments, and also on that of NOV1 and Tu80, phylogenetic tree has been constructed. Its topology is consistent with the accepted phylogenetic relationships among the species studied. The data available tend to support the assumption that the ancestor for the Tu80-like sequence might have arisen not later than 27-33 million years ago.

Amino Acid Sequence↗
PubMed1991

Somatic hypermutagenesis in immunoglobulin genes. I. Correlation between somatic mutations and repeats. Somatic mutation properties and clonal selection.

Based on the analysis of some immunoglobulin V-gene sequences, somatic mutations are assumed to occur by correction of complementary violations in heteroduplexes formed by direct or inverted repeats. Correlation between somatic mutations and repeats is investigated by a statistical weights method in 323 somatic substitutions in 14 V-genes. Assuming absence of correlation, the probability of observing data in the sample would be very low (0.00004). This result supports the idea that somatic mutations may arise from heteroduplex repair. The high frequency of these mutations in complementarity-determining regions (CDRs) of V-genes may be due to a high concentration of repeats in these regions. Analysis of somatic substitutions has revealed that stabilizing selection seems to provide conservation of framework regions (FRs) (which leads to preservation of the protein's three-dimensional structure). Positive selection may be provided by B-lymphocyte proliferation with large changes in CDRs.

Animals↗
PubMed1991

B2-like repetitive sequence from the X chromosome of the American mink (Mustela vison).

In analysis of the repeats from the mink X Chromosome (Chr), we have identified a B2-like repetitive sequence of 195 base pairs (bp) flanked by short direct repeats of 14 bp. It contains regions homologous to the split intragenic RNA polymerase III promoter and a 3' A-rich region followed by an oligo(dA) sequence. A feature of the repeat is the presence of a perfect polypyrimidine tract 22 bp in length absent from the known Alu- and Alu-like sequences. Alignment of the mink B2-like sequence and mouse B2-consensus sequence allowed us to estimate their similarity as 55%. The repeat is present in 1-2 x 10(5) copies per mink genome and 2-4 x 10(3) copies per X Chr. In situ hybridization analysis demonstrated a similar distribution pattern of the B2-like repeat along the length of all the mink chromosomes including the X. We also observed the presence of mink B2-like hybridizable sequence in the genomes of other Carnivora species.

Animals↗
PubMed1990

[Cloning and sequencing of immunoglobin lambda-chain cDNA in american mink (Mustela vison].

cDNA library in the lambda gt11 phage was constructed using poly (A+)-mRNA from mink spleen as a template. Immunoscreening of the library allowed the identification of 2 lambda-related clones containing 370 and 803 bp insertion (lambda IGL-1 and lambda IGL-2). Analysis of the primary structure of lambda IGL-2 demonstrated that it contains a large portion of V lambda-segment, J lambda-segment, C lambda-gene and its 3'-untranslated part. The nucleotide sequences known for the immunoglobulin genes were compared to the sequence of the lambda IGL-2 clone. The highest degree of homology was established for the rabbit lambda-genes, this being 63, 94 and 72% for the RF3 region of V lambda-segment, J lambda-segment and C lambda-region, respectively.

Animals↗
PubMed1989

[Theoretical analysis of mechanisms of spontaneous and induced mutations in DNA based on repeated sequences].

Mechanisms of spontaneous and chemically induced point mutations' emergence in DNA have theoretically been investigated using the statistical weight method. We have analysed 12 nucleotide sequences containing 95 point spontaneous mutations and 3 sequences comprising 30 mutations induced by such mutagens as 4'-hydroxymethyl-4,5',8-threemethylpsoralene, natrium bisulfite, hydroxylamine. The possibility of occurrence of point mutations by repair correction of heteroduplexes formed via mispairing of imperfect direct and inverted repeats in DNA has been studied. Statistically reliable connection of position of spontaneous mutations in DNA with repeats has been revealed for a number of nucleotide sequences. Statistically reliable connection of mutations induced by 4'-hydroxymethyl-4,5',8-threemethylpsoralene with imperfect repeats is also shown.

Animals↗
PubMedDate not supplied

Regression trees for analysis of mutational spectra in nucleotide sequences.

MOTIVATION: The study and comparison of mutational spectra is an important problem in molecular biology, because these spectra often reveal important features of the action of various mutagens and the functioning of repair/replication enzymes. As is known, mutability varies significantly along nucleotide sequences: mutations often concentrate at certain positions in a sequence, otherwise termed 'hotspots'. RESULTS: Herein, we propose a regression analysis method based on the use of regression trees in order to analyse the influence of nucleotide context on the occurrence of such hotspots. The REGRT program developed has been tested on simulated and real mutational spectra. For the G:C-->T:A mutational spectra induced by Sn1 alkylating agents (nine spectra), the prediction accuracy was 0. 99. AVAILABILITY: The REGRT program is available upon request from V.Berikov.

Algorithms↗
PubMedDate not supplied

GeneBuilder: interactive in silico prediction of gene structure.

MOTIVATION: Prediction of gene structure in newly sequenced DNA becomes very important in large genome sequencing projects. This problem is complicated due to the exon-intron structure of eukaryotic genes and because gene expression is regulated by many different short nucleotide domains. In order to be able to analyse the full gene structure in different organisms, it is necessary to combine information about potential functional signals (promoter region, splice sites, start and stop codons, 3' untranslated region) together with the statistical properties of coding sequences (coding potential), information about homologous proteins, ESTs and repeated elements. RESULTS: We have developed the GeneBuilder system which is based on prediction of functional signals and coding regions by different approaches in combination with similarity searches in proteins and EST databases. The potential gene structure models are obtained by using a dynamic programming method. The program permits the use of several parameters for gene structure prediction and refinement. During gene model construction, selecting different exon homology levels with a protein sequence selected from a list of homologous proteins can improve the accuracy of the gene structure prediction. In the case of low homology, GeneBuilder is still able to predict the gene structure. The GeneBuilder system has been tested by using the standard set (Burset and Guigo, Genomics, 34, 353-367, 1996) and the performances are: 0.89 sensitivity and 0.91 specificity at the nucleotide level. The total correlation coefficient is 0.88. AVAILABILITY: The GeneBuilder system is implemented as a part of the WebGene a the URL: http://www.itba.mi. cnr.it/webgene and TRADAT (TRAncription Database and Analysis Tools) launcher URL: http://www.itba.mi.cnr.it/tradat.

Amino Acid Sequence↗
PubMedDate not supplied

[The mutational spectra of gene p53 in different types of tumors].

The comparative analysis of the frequencies of nucleotide exchanges in mutational spectra of gene p53 (5-8 exons) between germline cancer-prone families (Li-Fraumeni syndrome), between somatic mutations in the tumors of different histogenesis and cell lines, obtained from them, was carried out. The nucleotide positions with high level of mutation events (mutational "hot spots"), typical for germline mutational spectra, tissue-specific patterns of their disappearing and appearing of new ones in solid tumors in vivo, nearly complete absence of "hot spots" in lymphomas and cell lines in vitro were revealed. The obtained results allowed to suggest, that one of the leading factor controlling hot-spots distribution in 5-8 exons of gene p53 is the specificity of cell division conditions in vivo and in vitro.

Base Sequence↗
PubMedDate not supplied

[Use of a rank correlation coefficient for comparing mutational spectra].

It is suggest to use the Kendall's rank correlation coefficient tau for the analysis of correlation between mutation spectra. The results of computer simulations and analysis of real spectra showed that the approach can be recommended for the analysis of mutation spectra.

Bacterial Proteins↗