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Genomics

Find indexed PubMed genomics citations. Search gene expression, sequencing and genetic variation in titles, abstracts and supplied subjects, then open the PubMed record.

At least 973 records · Page 54Linked to original sources

[From genomics to post-genomics: back to the origins?].

The purpose of this review is to emphasize the multiplicity and importance, physiological and pathological, of gene regulation levels which operate after the initiation step of transcription. Albeit crucial, this step is only the first one of a long cascade of events which eventually end up in the selection of functional messengers appropriate to the nature of the cells and to their immediate needs. Throughout this long pathway, of which only a few steps will be mentioned here, this review will attempt to address the central role played by RNA, not only as a substrate but as an actor of its own regulation. Emphasis will be put on the numerous connections with pathology up to the development of new therapeutics specifically targeting RNA. It highlights the perennity of basic questions, nearly half a century old, for which genomics, short of new concepts, will provide the databases and tools required to access to the immense field of functional genomics, the only one likely to bring relevant answers for therapeutics.

Animals↗

Genomic alterations detected by comparative genomic hybridization in primary lung adenocarcinomas with special reference to the relationship with DNA ploidy.

To clarify the clinicopathological and biological significance of genomic alterations in pulmonary adenocarcinomas, we examined chromosomal DNA sequence copy number aberrations (DSCNAs) and DNA ploidy in 42 surgically resected specimens by comparative genomic hybridization (CGH) and laser scanning cytometry (LSC), respectively. The number of DSCNA did not affect the size of carcinoma or number of nodal metastasis. More than 60% of carcinomas showed a 1q21-23 gain or 13q21 loss. Gains of 9q22-33 and 10q26-qter and a loss of 15q14-qter were significantly associated with nodal metastasis (p<0.05). Of 42 pulmonary adenocarcinomas, 32 (76%) showed DNA aneuploidy. The number of DSCNAs in aneuploid carcinomas was larger than that in diploid carcinomas (p<0.01). Our results suggest that diploid and aneuploid types are cytogenetically different in pulmonary adenocarcinomas and aneuploid carcinomas are genetically more unstable and aggressive than diploid carcinomas.

Adenocarcinoma↗

Screening of genomic imbalances in glioblastoma multiforme using high-resolution comparative genomic hybridization.

Comparative genomic hybridization (CGH) is a molecular cytogenetic technique that allows the genome-wide analysis of DNA sequence copy number differences. We applied conventional CGH and the recently developed high-resolution CGH (HR-CGH) to tumour samples from 18 patients with glioblastoma multiforme (GBM) in order to compare the sensitivity of CGH and HR-CGH in the screening of chromosomal abnormalities. The abnormalities were studied in topologically different central and peripheral tumour parts. A total of 78 different changes were observed using CGH (0-16 per tumour, median 3.5) and 154 using HR-CGH (0-21 per tumour, median 6). Using HR-CGH, losses were more frequent than gains. The representation of the most prominent changes revealed by both methods was similar and was comprised of the amplification of 7q12 and 12q13-q15, the gain of 7, 3q and 19, and the loss of 10, 9p, and 13q. However, HR-CGH detected certain other abnormalities (the loss of 6, 14q, 15q and 18q, and the gain of 19), which were rarely revealed by CGH. Using HR-CGH, the numbers and types of chromosomal changes detected in the central and peripheral parts of GBM were almost the same. The loss of chromosomes 10 and 9p and the gain of chromosomes 7 and 19 were the most frequent chromosomal alterations in both tumour parts. Our results from the GBM analysis show that HR-CGH technology can reveal new, recurrent genetic alterations involving the genes known to participate in tumorigenesis and in the progression of several human malignancies, thus allowing for a more accurate genetic characterization of these tumours.

Adult↗

[Study of the structure-function organization of the variola virus genome. IV. Sequencing and analysis of the nucleotide sequence of the right terminus of the India-1967 strain genome].

Sequencing and computer analysis of the variola major virus strain India-1967 (VAR-IND) genome segment (53,018 bp) from the right terminal region have been carried out. Fifty nine potential open reading frames (ORFs) of over 60 amino acid residues have been identified. Structure-function organization of VAR-IND DNA segment under study was compared with the previously reported sequences from the analogous genomic regions of vaccinia virus strains Copenhagen (VAC-COP) and Western Reserve (VAC-WR) and variola virus strain Harvey (VAR-HAR). Multiple distinctions in the genetic map of VAR-IND from VAC-COP and VAC-WR have been revealed along with the high similarity to the corresponding VAR-HAR segment. Possible functions of the predicted viral proteins and the effect of their differences on the features of orthopoxviruses are discussed.

Amino Acid Sequence↗

[A full-size DNA copy of the tick-borne encephalitis virus genome. I. Analysis of the 5'- and 3'-terminal noncoding regions of the genome].

Using reverse transcription and the polymerase chain reaction, cDNA fragments of noncoding regions of the tick-borne encephalitis virus (TBEV) genome were obtained. These fragments were cloned into a pGEM3 vector, and their nucleotide sequences were determined. The heterogeneity of the 3'-terminal untranslated region of the TBEV RNA was revealed. To create a stable full-size DNA copy of the TBEV genome, four cDNA variants differing in length and structure of the 3'-terminal fragment of the viral RNA were cloned into a pBR322-derived vector.

Base Sequence↗

[Structure-activity organization of the variola virus genome. III. Sequencing and analysis of the nucleotide sequence of the conserved region of HindIII-F, -N-, and -A-fragments of the India 1967 strain genome].

Computer analysis of variola major virus (VAR) genomic fragment bounded by open reading frames (ORFs) D1R and A33L which is 47,961 bp long revealed 46 potential ORFs. The VAR proteins were compared with the analogous proteins of vaccinia virus strain Copenhagen. The subunits of DNA-dependent RNA polymerase, as well as the transcription factors, mRNA capping enzymes, and proteins necessary for the virion morphogenesis proved to be highly conservative within orthopoxviruses. The most pronounced differences between the VAR genome fragment under study and the corresponding vaccinia virus fragment were revealed in the vicinity of the gene encoding the A-type inclusion body protein. The possible functions of the analyzed viral proteins are discussed.

Amino Acid Sequence↗

[Comparison between HGV genome and HGBV-C genome].

New hepatitis viruses, hepatitis G virus(HGV) and hepatitis GB virus C(HGBV-C), were reported from two groups of researchers. Now these two are thought to be similar but HGV genome(U44402) and HGBV-C genome(U36380) do not have the same sequence. We compare these two sequences in both nucleotide and aminoacid analyses. Homology of nucleotide between HGV and HGBV-C is 83.8% in 5'NC region, 88.8% in core, 85.1% in E1, 85.7% in E2, 85.1% in NS2-3, 84.5% in NS4A, 86.8% in NS4B-5A, 88.6% in NS5B and 18.0% in 3'NC. The length of 3'NC is quite different between HGV and HGBV-C. Homology of aminoacid between these two viruses is 82.9% in core region, 87.3% in E1, 91.0% in E2, 97.4% in NS2-3, 93.8% in NS4A, 96.2% in NS4B-5A and 96.6% in NS5B. Especially helicase and replicase regions are highly conserved in 99.0% and 92.7% of aminoacid homology, respectively.

Amino Acid Sequence↗

Another side of genomics: synthetic biology as a means for the exploitation of whole-genome sequence information.

The successful completion of the Human Genome Project and other sequencing projects opened the door for another quantum jump in science advancement. The most important public sequence databases are doubling in size every 18 months. By revealing the genetic program of many organisms, these efforts endow biologists with the ability to study the basic information of life in toto as an initial step toward a comprehensive understanding of the complexity of entire organisms. We review the area of synthetic biology, defined as the making and use of biosystems founded on the chemical synthesis of the coding DNA (and potentially RNA). The recent developments discussed here introduce a rich source of oligonucleotides to the field: in situ synthesised microarrays, which in fact represent nothing else but matrix nucleic acid synthesisers. With this new way of producing the oligonucleotides used in the making of synthetic genes in a very cost-effective manner, the field of synthetic biology can be expected to change dramatically in the next decade. Synthetic genes will then be the tools of choice to obtain any sequence at any time in any laboratory.

Base Sequence↗

Realizing the potential of the genome revolution: the genomes to life program.

The systems biology revolution is proceeding along multiple pathways as different science agencies and the private sector have adopted strategies suited to their particular needs and cultures. To meet this challenge, the U.S. Department of Energy has developed the Genomes to Life (GTL) program. A central focus of GTL is environmental microbial biology as a way to approach global environmental problems, and its key goal is to achieve, over the next 10 to 20 years, a basic understanding of thousands of microbes and microbial systems in their native environments. This focus demands that we address huge gaps in knowledge, technology, computing, data storage and manipulation, and systems-level integration.

Biotechnology↗

Gains, losses, and amplifications of genomic materials in primary gastric cancers analyzed by comparative genomic hybridization.

By means of comparative genomic hybridization (CGH), we screened 58 primary gastric cancers for changes in copy number of DNA sequences. We detected frequent losses on Ip32-33 (21%), 3p21-23 (22%), 5q14-22 (36%), 6q16 (26%), 9p21-24 (22%), 16q (21%), 17p13 (48%), 18q11-21(33%), and 19(40%). Gains were most often noted at I p36 (22%), 8p22-23 (24%), 8q23-24 (29%), 11q12-13 (24%), 16p(21%), 20p (38%), 20q (45%), Xp21-22(38%), and Xq21-23 (43%), with high-level amplifications at 6p21(2%),7q31(10%), 8p22-23(5%), 8q23-24 (7%), 11q13(4%), 12p12-13(4%), 17q21(2%), 19q12-13(2%), and 20q13(2%). High-level amplification at 8p22-23 has never been reported in any other cancer type and its frequency was as high as that reported for the MYC, MET, and KRAS genes. We narrowed down the smallest common amplicon to 8p23.1 by reverse-painting FISH to prophase chromosomes. Southern blot analysis using one EST marker (D38736) clearly demonstrated that amplification of this exon-like sequence had occurred in all three tumors in which amplifications at 8p22-23 had been detected by CGH. Our data provide evidence for several, previously undescribed, genomic aberrations that are characteristic of gastric cancers.

Blotting, Southern↗

Characterization of a 5.3 Mb deletion in 15q14 by comparative genomic hybridization using a whole genome "tiling path" BAC array in a girl with heart defect, cleft palate, and developmental delay.

High-resolution array CGH utilizing sets of overlapping BAC and PAC clones ("tiling path") covering the whole genome is a powerful novel tool for fast detection of submicroscopic chromosome deletions or duplications. We describe the successful application of a submegabase resolution whole genome "tiling path" BAC array to confirm and characterize a de novo interstitial deletion of chromosome 15. The deletion has a size of 5.3 Mb and is located within chromosome band 15q14, distal to the Prader-Willi/Angelman region. The affected girl had a heart defect, cleft palate, recurrent infections, and developmental delay. In contrast to GTG banding, array CGH determined the exact number of deleted genes and thus allowed the identification of candidate genes for cleft palate (GREM1, CX36, MEIS2), congenital heart defect (ACTC, GREM1, CX36, MEIS2), and mental retardation (ARHGAP11A, CHRNA7, CHRM5).

Adult↗

Comparative genomic hybridization analysis of primary cutaneous B-cell lymphomas: identification of common genomic alterations in disease pathogenesis.

To investigate genetic alterations in primary cutaneous B-cell lymphomas (PCBCLs), we have analyzed 29 cases of PCBCL. Comparative genomic hybridization showed chromosome imbalances (CIs) in 12 cases (41%). The mean number of CIs per sample was 2.05 +/- 2.97, with gains (1.48 +/- 2.38) more frequent than losses (0.56 +/- 1.40). The common regions of gains were 18/18q (50%), 7/7p (42%), 3/3q (33%), 20 (33%), 1p (25%), 12/12q (25%), and 13/13q (25%), whereas loss of 6q was frequent (42%). Among the different subsets of PCBCLs, CI was seen in 50% of diffuse large-cell lymphomas (DLCLs), 33% of marginal zone lymphomas, and 8% of follicle center cell lymphomas and unclassified lymphomas. A similar pattern of CI was observed in these lymphomas, but loss of 6q and gains of 3/3q were present only in DLCLs. Microarray-based genomic analysis of four DLCL cases identified oncogene gains of SAS/CDK4 (12q13.3) in three cases and MYCL1 (1p34.3), MYC (8q24), FGFR2 (10q26), BCL2 (18q21.3), CSE1L (20q13), and PDGFB (22q12-13) in two cases, whereas losses of AKT1 (14q32.3), IGFR1 (15q25-26), and JUNB (19p13.2) were identified in three cases, and losses of FGR (1p36), ESR (6q25.1), ABL1 (9q34.1), TOP2A (17q21-22), ERBB2 (17q21.2), CCNE1 (19q13.1), and BCR (22q11) were each identified in two cases. In addition, real-time-polymerase chain reaction detected amplification of BCL2 in 5 of 29 cases. These findings suggest that there are complex but consistent genetic alterations associated with the pathogenesis of PCBCLs.

Chromosome Aberrations↗

Identification of extensive genomic loss and gain by comparative genomic hybridisation in malignant astrocytoma in children and young adults.

Although astrocytomas are the most common central nervous system tumours in all age groups, there is substantial evidence that tumours arising in young patients (< 25 years of age) do not have the same genetic abnormalities that are characteristic of tumours in older patients. Furthermore, novel, consistent changes have not been identified in astrocytomas in children and young adults. We analysed 13 malignant astrocytomas from young patients using comparative genomic hybridisation. Regions of genomic imbalance were identified in 10 cases. The most common recurrent copy number aberrations were loss of 16p (54% of cases), 17p (38%), 19p (38%), and 22 (38%) and gain on 2q (38%), 12q (38%), 13 (38%), 4q (31%), 5q (31%), and 8q (31%). Seven regions of high copy number amplification were observed at 8q21-22 (three cases), 7q22-23 (two cases), and 1p21-22, 2q22, 12q13-pter, 12q15-21, and 13q11-14 (one case each). This study provides evidence of new characteristic chromosomal imbalances from which potential candidate genes involved in the development of malignant astrocytoma in children and young adults may be identified.

Adolescent↗

Comparative genomic hybridization analysis of human sarcomas: I. Occurrence of genomic imbalances and identification of a novel major amplicon at 1q21-q22 in soft tissue sarcomas.

Comparative genomic hybridization (CGH) was recently developed as a tool to survey entire genomes for variations in DNA sequence copy numbers. We have applied this technique to detect and map amplified regions in 54 soft tissue sarcomas. Aberrations were detected by visual analysis of hybridizations or contrast-enhanced digital images, followed by quantitative digital ratio imaging of the aberrant chromosomes. Several tumors showed increased DNA sequence copy number at 12q14, as expected. However, CGH analysis detected amplification of 12q14 also in some tumors where neither MDM2 nor CDK4 was amplified, suggesting that another as yet unknown gene(s) may drive amplification of this region in sarcomas. Furthermore, a novel recurring amplicon was detected at 1q21-q22. DNA amplifications coinciding with this segment were as frequent as those observed for 12q14, indicating that 1q21-q22-linked gene(s) may also play an important role in the development and/or progression of human soft tissue sarcomas.

Animals↗

Comparative genomic hybridization analysis of tonsillar cancer reveals a different pattern of genomic imbalances in human papillomavirus-positive and -negative tumors.

Our aim was to map and compare genomic imbalances in human papillomavirus (HPV)-positive and -negative squamous cell carcinomas of the tonsil. Twenty-five primary carcinomas were analyzed by comparative genomic hybridization. Fifteen (60%) were found to be HPV-positive by PCR, and the majority were HPV-16. There were statistically significant differences in the distribution of DNA gains and losses between the HPV-positive and -negative samples. Eleven of 15 HPV-positive samples (73%) showed gain on chromosome 3q24-qter, while only 4/10 (40%) HPV-negative samples had the same gain (p = 0.049). Furthermore, 4/10 (40%) HPV-negative samples but no HPV-positive samples had gain on chromosome 7q11.2-q22 (p = 0.017). As expected, and similar to previous studies, patients with an HPV-positive tumor had a statistically significantly better disease-specific survival than patients with an HPV-negative tumor (p = 0.002). The most common changes, e.g., gain on 3q or 8q, loss on 11q or 13 and loss on chromosome 7q in HPV-negative tumors, did not have any influence on prognosis. However the number of cases in each subgroup was limited.

Adult↗

Comparison of genomic abnormalities between BRCAX and sporadic breast cancers studied by comparative genomic hybridization.

Very little is known about the chromosomal regions harbouring genes involved in initiation and progression of BRCAX-associated breast cancers. We applied comparative genomic hybridization (CGH) to identify the most frequent genomic imbalances in 18 BRCAX hereditary breast cancers and compared them to chromosomal aberrations detected in a group of 27 sporadic breast cancers. The aberrations observed most frequently in BRCAX tumours were gains of 8q (83%), 19q (67%), 19p (61%), 20q (61%), 1q (56%), 17q (56%) and losses of 8p (56%), 11q (44%) and 13q (33%). The sporadic cases most frequently showed gains of 1q (67%), 8q (48%), 17q (37%), 16p (33%), 19q (33%) and losses of 11q (26%), 8p (22%) and 16q (19%). Losses of 8p and gains 8q, 19 as well as gains of 20q (with respect to ductal tumours only) were detected significantly more often in BRCAX than in sporadic breast cancers. Analysis of 8p-losses and 8q-gains showed that these aberrations are early events in the tumorigenesis of BRCAX tumors. The findings of this report indicate similarities between BRCAX and BRCA2 tumours, possibly suggesting a common pathway of disease. These findings need confirmation by more extensive studies because only a limited number of cases were analysed and there are relatively few reports published.

Adult↗

14q+ marker chromosome in an EBV-genome-negative lymph node without signs of malignancy in a patient with EBV-genome-positive nasopharyngeal carcinoma.

In a patient with an EBV-genome-positive nasopharyngeal carcinoma, an EBV-genome-negative inguinal lymph node without histological evidence of malignant lymphoma or metastatic carcinoma growth was found to contain a 14q+ marker chromosome, identified as an 8;14 translocation, in all cells analyzed. This observation indicates that chromosome aberrations may precede histological signs of malignancy. The possible implication of this finding in relation to the postulated role of the 14q+ marker and lymphoma development is discussed.

Adult↗

Acquisition of a fourth genomic segment in bacteriophage phi 6, a bacteriophage with a genome of three segments of dsRNA.

Bacteriophage phi 6 has a genome of three segments of double-stranded RNA enclosed in a polyhedral procapsid. Packaging of individual segments is dependent upon unique packaging sequences near the 5' ends of the segments. We have prepared deletions in segments L and M that decrease their size by half. Phages with these deletions can be propagated on host strains carrying plasmids with complementing genes. The deletion segments are present in two copies per virion. Phage carrying a deletion segment can acquire the transcript of the complementing plasmid if the latter has a packaging sequence. If the packaging sequence is homologous to that of the deletion segment, acquisition occurs at high frequency. If it is heterologous, then recombination exchanges the heterologous packaging sequence for a homologous one or it attaches the transcript to one of the other genomic segments.

Bacteriophages↗