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Biomedical subjects

A V Baranova

Publications and source records attributed to A V Baranova.

14 recordsLinked to original sources

[Search for transcribed segments in the region of q14.3 of human chromosome 13 in silico].

Using computer-aided genomic methods, a complete map of the expressed sequence tags (EST) located in the human genome region 13q14.3 between the STS markers, D13S810 and D13S1469, was constructed. A total of 62 EST clusters were formed, of which 12 clusters corresponded to the already known human genes, 4 clusters represented pseudogenes, and 10 clusters were new human genes. The use of the method of reverse transcription in combination with polymerase chain reaction (RT-PCR) provided experimental confirmation of the existence of mRNA transcripts for the novel human genes revealed in silico.

Base Sequence↗

A new human gene KCNRG encoding potassium channel regulating protein is a cancer suppressor gene candidate located in 13q14.3.

We report the primary characterization of a new gene KCNRG mapped at chromosome band 13q14.3. This gene includes three exons and has two alternatively spliced isoforms that are expressed in normal tissues and in some tumor cell lines. Protein KCNRG has high homology to tetramerization domain of voltage-gated K+ channels. Using the patch-clamp technique we determined that KCNRG suppresses K+ channel activity in human prostate cell line LNCaP. It is known that selective blockers of K+ channels suppress lymphocyte and LNCaP cell line proliferation. We suggest that KCNRG is a candidate for a B-cell chronic lymphocytic leukemia and prostate cancer tumor suppressor gene.

Amino Acid Sequence↗

[Fundamental and applied aspects of comparative genomics of vertebrates].

The Human Genome Project stimulated the development of efficient strategies and relevant hardware for complete genome sequencing. The comparative genomic approach extends the possibilities of using the sequencing data to identify new genes or conserved regulatory regions by means of nucleotide sequence alignment of the particular regions of the mouse and human genomes, or to trace the evolutionary events resulting in the genome structure of modern mammals. The review focuses on the use of new molecular cytogenetic methods along with computer-aided analysis of the genomes in vertebrates. Several factors hindering data analysis are considered. The currently available information on gene evolution rate inferred from comparative genomic data is presented. The origin and evolution of the genomes of several species are discussed.

Animals↗

In silico screening for tumour-specific expressed sequences in human genome.

A computer-based differential display tool named HsAnalyst has been developed and successfully used for the comparison of expression patterns in a set of tumours versus a set of normal tissues. A list of EST clusters highly represented in tumours and rarely observed in normal tissues has been developed as a resulting output file of the program. These differentially expressed EST clusters (genes) can be useful for developing new tumour markers and prognostic indicators for a wide set of human malignancies. Tumour-specific protein-coding genes may be considered a manifestation of tumour-specific gene expression.

Databases, Genetic↗

[A new pentanucleotide STR-marker, located in the intron of the ING1 tumor suppressor gene and its allelic polymorphism].

DNA samples of unrelated subjects from the Volga-Ural region of Russia were examined to study allele polymorphism of the pentanucleotide repeat (TTGTG)8 localized to an intron of the tumor suppressor gene ING1. STR marker was registered in the EMBL database with the accession number AJ277387. In a sample of 119 individuals, three pentanucleotide alleles consisting of seven, eight, and nine repeated monomers were revealed. The allele frequencies were 0.24, 0.74, and 0.02, respectively. Heterozygosity was 0.45. On the basis of these data, the repeat can be regarded as a polymorphic STR marker for the ING1 gene and used in population and clinical studies.

Alleles↗

[Evolutionarily-conserved gene CKAP2,located in region 13q14.3 of the human genome, is frequently rearranged in various tumors].

The human CKAP2 gene, which is involved in diffuse large B-cell lymphomas, was localized via screening the GeneBridge 4 somatic cell radiation hybrid panel by means of the polymerase chain reaction (PCR). The CKAP2 gene was mapped between the WI-15460 and WI-3673 markers at the boundary between regions 13q14.3 and 13q21.1, at the distance of 14.39 cR (with 4.8 cR per cM) from the WI-5867 framework marker (lod score > 2.26). The human CKAP2 gene displayed high homology to mouse and rat expressed orthologs, A CKAP2-like sequence was found in human chromosome 14 and assumed to be a pseudogene resulting from duplication and subsequent mutations of the CKAP2 gene on chromosome 13. A possible role of the CKAP2 gene in oncogenesis associated with deletions and rearrangements of region 13q14.3-21.1 is discussed.

Animals↗

[Transcription map of the 13q14 region, frequently deleted in B-cell chronic lymphocytic leukemia patients].

Deletions in the region located between the STS markers D13S1168 and D13S25 on chromosome 13 are the most frequent genomic changes in patients with B-cell chronic lymphocytic leukemia (B-CLL). After sequencing of this region, two novel candidate genes were identified: C13orf1 (chromosome 13 open reading frame 1) and PLCC (putative large CLL candidate). Analysis of the repeat distribution revealed two subregions differing in composition of repetitious DNA and gene organization. The interval D13S1168-D13S319 contains 131 Alu repeats accounting for 24.8% of its length, whereas the interval GCT16C05-D13S25, which is no more than 180 kb away from the former one is extremely poor in Alu repeats (4.1% of the total length). Both intervals contain almost the same amount of the LINE-type repeats L1 and L2 (20.3 and 21.24%, respectively). In the chromosomal region studied, 29 Alu repeats were found to belong to the evolutionary young subfamily Y, which is still capable of amplifying. A considerable proportion of repeats of this type with similar nucleotide sequences may contribute to the recombinational activity of the chromosomal region 13q14.3, which is responsible for its rearrangements in some tumors in humans.

Chromosome Deletion↗

[Cosmid libraries containing DNA from human chromosome 13].

We characterized two cosmid libraries constructed from flow-sorted chromosome 13 at the Imperial Cancer Research Fund (ICRF), UK (13,000 clones) and Los Alamos National Laboratory (LANL), USA (17,000 clones). After storage for two years, clones showed high viability (95%) and structural stability. EcoR I and Hind III restriction patterns were studied in more than 500 ICRF and 200 LANL cosmids. The average size of inserts was shown to be 35-37 kb in both the libraries. Most cosmids (83% and 93% of ICRF and LANL libraries, respectively) exceed the lower size limit of DNA fragments that can be packaged and represent a good source for physical mapping of chromosome 13. Total length of inserts is four and five genome equivalents in the ICRF and LANL libraries, respectively. ICRF cosmids showed hybridization to 22 of 24 unique probes tested, which corresponds to a 90% probability of having any DNA fragment represented in the library. More than 1 Mb of chromosome 13 is overlapped by 90 cosmids of 22 groups revealed. A chromosomal region of more than 150 kb, containing the ATP1AL1 gene for alpha-1 peptide of Na+, K(+)-ATPase, is covered by 12 cosmids forming a contig. The results of restriction and hybridization analyses are stored in a CLONE database. These data and all the cosmids described are publicly available.

Chromosome Mapping↗

[Structural-functional characteristics of the 13q14 region of the human genome in the search for potential tumor suppressor genes].

Works on chromosome 13 mapping supported by the Russian program Human Genome are reviewed. Emphasis is placed on studies of region 13q14.3, which is often lost in some human tumors and potentially contains tumor suppressor genes (TSG). A strategy of TSG search is described. As the resolution of genome analysis improved, a minimal overlap of genetic loss in B-cell chronic lymphocytic leukemia (B-CLL) was established for chromosome 13. A map of expressed sequences was constructed for the region containing the overlap, and candidate TSG of chromosome 13q14 were identified. The candidate genes were analyzed both structurally and functionally, and their possible role in tumorigenesis was considered. Assuming haploinsufficiency as a genetic mechanism controlling B-CLL, a new strategy was proposed for mutation screening aimed at identifying potential TSG of region 13q14.

Chromosomes, Human, Pair 13↗