Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “reference genome”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed2001

Genetic crossover interference in the human genome.

Positive crossover interference refers to the phenomenon that the occurrence of a crossover reduces the probability of another crossover in its vicinity. There have been studies reporting the presence of positive interference in humans. Some studies have also found evidence suggesting within and between chromosomal interference heterogeneity on some of the chromosomes. However, there has been no systematic study of interference and interference heterogeneity in the whole human genome, using pedigree data without first inferring crossovers. In this paper, we studied the Chi-square interference model and other models extensively to compare the relative performance of each of these models for accounting for interference and measuring strength of interference. Our results showed that the Chi-square model consistently fitted the data well and provided easily interpretable estimates of interference strength. The Chi-square model was then used to study interference and interference heterogeneity within and between chromosomes. We found strong evidence of positive interference in the whole human genome. Our results also indicated that the level of interference was fairly constant in most parts of the genome, but there was some evidence suggesting that the levels of interference for two of the chromosomes were different from the rest. We also found evidence of within chromosomal interference heterogeneity for several of the chromosomes.

Chromosomes↗
PubMed2005

In silico reconstruction of the metabolic pathways of Lactobacillus plantarum: comparing predictions of nutrient requirements with those from growth experiments.

On the basis of the annotated genome we reconstructed the metabolic pathways of the lactic acid bacterium Lactobacillus plantarum WCFS1. After automatic reconstruction by the Pathologic tool of Pathway Tools (http://bioinformatics.ai.sri.com/ptools/), the resulting pathway-genome database, LacplantCyc, was manually curated extensively. The current database contains refinements to existing routes and new gram-positive bacterium-specific reactions that were not present in the MetaCyc database. These reactions include, for example, reactions related to cell wall biosynthesis, molybdopterin biosynthesis, and transport. At present, LacplantCyc includes 129 pathways and 704 predicted reactions involving some 670 chemical species and 710 enzymes. We tested vitamin and amino acid requirements of L. plantarum experimentally and compared the results with the pathways present in LacplantCyc. In the majority of cases (32 of 37 cases) the experimental results agreed with the final reconstruction. LacplantCyc is the most extensively curated pathway-genome database for gram-positive bacteria and is open to the microbiology community via the World Wide Web (www.lacplantcyc.nl). It can be used as a reference pathway-genome database for gram-positive microbes in general and lactic acid bacteria in particular.

Amino Acids↗
PubMed1993

The GDB Human Genome Data Base: a source of integrated genetic mapping and disease data.

The GDB Human Genome Data Base refers collectively to GDB and OMIM, Online Mendelian Inheritance in Man. GDB and OMIM are linked databases that provide an international repository for information generated by the Human Genome Initiative. GDB contains human gene mapping data, while OMIM offers the text of Dr. Victor A. McKusick's catalog of genetic disease and phenotype descriptions. These databases, updated and edited continuously, integrate bibliographic and full-text information with several types of mapping data. They are accessible through a flexible interface and are available through SprintNet and the Internet to the scientific community without cost. This paper provides an overview of the context, development, structure, content, and use of these databases.

Chromosome Mapping↗
PubMedDate not supplied

[The loss of CpG dinucleotides from DNA. I. Methylated and non-methylated genome compartments in eukaryotes with different levels of 5-methylcytosine in DNA].

The methylation of cytosine residues in CpG significantly increases the frequency of m5CpG----TpG transitions in DNA and CpG dinucleotides are eliminated from the genome (CpG-suppression). In the millions of years of vertebrates evolution about 3 mol% of 5-methylcytosine have disappeared from their genome, i.e., 2-3-fold more than the amount persisting in the DNA of the now extant species. A computer analysis has been carried out of neighboring b.p. frequencies in more than 2500 sequenced genes of different species in the EMBL bank with an overall extension of over 3000 kb. It has been found that CpG methylated sites exhibit a highly irregular distribution pattern in the genome of eucaryotes. The majority of the vertebrate sequences (92%) bears the impress of a significant lack of CpG and an excess of TpG+CpA; therefore they may be referred to the genome methylated compartment. A group of genes has been discovered (about 8%) where CpG must have never been subjected to methylation. In invertebrates, such a nonmethylated compartment makes up 59% of the genome and in eubacteria--85%. A brief list of genes, belonging to the methylated and the non-methylated compartments of the invertebrate and yeast genome, is given. It has been established that the mean value of CpG-suppression in genes is directly proportional to the methylation level of total DNA in different species.

5-Methylcytosine↗
PubMed2005

The genome and the nucleus: a marriage made by evolution. Genome organisation and nuclear architecture.

Genomes are housed within cell nuclei as individual chromosome territories. Nuclei contain several architectural structures that interact and influence the genome. In this review, we discuss how the genome may be organised within its nuclear environment with the position of chromosomes inside nuclei being either influenced by gene density or by chromosomes size. We compare interphase genome organisation in diverse species and reveal similarities and differences between evolutionary divergent organisms. Genome organisation is also discussed with relevance to regulation of gene expression, development and differentiation and asks whether large movements of whole chromosomes are really observed during differentiation. Literature and data describing alterations to genome organisation in disease are also discussed. Further, the nuclear structures that are involved in genome function are described, with reference to what happens to the genome when these structures contain protein from mutant genes as in the laminopathies.

Animals↗
PubMed2006

Structural variants: changing the landscape of chromosomes and design of disease studies.

The near completeness of human chromosome sequences is facilitating accurate characterization and assessment of all classes of genomic variation. Particularly, using the DNA reference sequence as a guide, genome scanning technologies, such as microarray-based comparative genomic hybridization (array CGH) and genome-wide single nucleotide polymorphism (SNP) platforms, have now enabled the detection of a previously unrecognized degree of larger-sized (non-SNP) variability in all genomes. This heterogeneity can include copy number variations (CNVs), inversions, insertions, deletions and other complex rearrangements, most of which are not detected by standard cytogenetics or DNA sequencing. Although these genomic alterations (collectively termed structural variants or polymorphisms) have been described previously, mainly through locus-specific studies, they are now known to be more global in occurrence. Moreover, as just one example, CNVs can contain entire genes and their number can correlate with the level of gene expression. It is also plausible that structural variants may commonly influence nearby genes through chromosomal positional or domain effects. Here, we discuss what is known of the prevalence of structural variants in the human genome and how they might influence phenotype, including the continuum of etiologic events underlying monogenic to complex diseases. Particularly, we highlight the newest studies and some classic examples of how structural variants might have adverse genetic consequences. We also discuss why analysis of structural variants should become a vital step in any genetic study going forward. All these progresses have set the stage for a golden era of combined microscopic and sub-microscopic (cytogenomic)-based research of chromosomes leading to a more complete understanding of the human genome.

Chromosomes↗
PubMed1995

Genetic differences in recombination frequency in the pig (Sus scrofa).

A comparison has been performed on 3 recently published linkage maps of the pig, hereafter designated as the American (A), European (E), and Swedish (S) maps. The cumulated distances between common markers in these 3 maps were in the ratio 1.00 (A):0.88 (E):0.77 (S), in keeping with the ratio of the percentages of domestic genome in the reference families used to build the corresponding maps, i.e., 1.00 (A):0.81 (E):0.50 (S). From further recombination frequencies reported in wild boars (in the S report), the wild pig genome length (in centimorgans) is expected to represent 66% of the domestic pig genome length. These observations tend to confirm a general result of Burt and Bell (Nature (London), 326: 803-805 (1987)), showing higher chiasma frequencies in domestic mammalian species compared with wild species. Consequences for mapping studies are discussed.

Animals↗
PubMed2003

FBSA: feature-based sequence alignment technique for very large sequences.

The ability to align pairs of very large molecular sequences is essential for a range of comparative genomic studies. However, given the complexity of genomic sequences, it has been difficult to devise a systematic method that can align - even within the same species - pairs of large sequences. Most existing approaches typically attempt to align nucleotide sequences while ignoring valuable features contained within them, eg they filter out low-complexity regions and retroelements before aligning the sequences. However, features are then added post-alignment for visualisation and analysis purposes. We argue that repetitive elements and other features (such as genes, exons and regulatory elements) should be part of the alignment process. A hierarchical approach that aligns the biologically relevant features before aligning the detailed nucleotide sequences has a number of interesting characteristics: (1) features define 'alignment anchor points' that can guide meaningful nucleotide alignment; (2) features can be weighted; (3) a hierarchical approach would identify only meaningful regions to be aligned; (4) nucleotide sequences can be described as sequences of features and non-features, providing a natural mechanism to divide the sequences for processing; and (5) computational speed is significantly faster than other approaches. In this paper, we describe and discuss a feature-based approach to aligning large genome sequences. We refer to this as 'feature-based sequence alignment'.

Algorithms↗
PubMed2006

Integration of genomic and metabonomic data in systems biology--are we 'there' yet?

The measurement of genes, proteins and metabolites has gained increasing acceptance as a means by which to study the response of an organism to stimuli, whether they are environmental, genetic, pharmacological, toxicological, etc. Typically referred to as genomics, proteomics, and metabonomics or metabolomics, respectively, these methods as independent entities have undoubtedly provided new biological insight that was not attainable a decade ago. Not surprisingly, scientists continue to push the boundaries to extract knowledge from data, and it is currently recognized that the full realization of these technologies is limited by a lack of tools to enable data integration. Integration of these 'omic datasets, or integromics, is desirable as it links the individual biological elements together to provide a more complete understanding of dynamic biological processes. Accordingly, in addition to developing new data analysis methods to extract further details from each of the high-content datasets individually, effort is also being expended to create or improve statistical methods, databases, annotations and pathway mapping to maximize our learning. There are several recent examples, in both mammalian and non-mammalian systems, in which genes, proteins and/or metabolites have been integrated using either biology- or data-driven strategies. Herein, key findings are reviewed, gaps in our current tools and technologies are identified and illustrated, and perspective is provided on the potential of integromics in biological research.

Acetaminophen↗
PubMed2005

A rhesus macaque radiation hybrid map and comparative analysis with the human genome.

The genomes of nonhuman primates are powerful references for better understanding the recent evolution of the human genome. Here we compare the order of 802 genomic markers mapped in a rhesus macaque (Macaca mulatta) radiation hybrid panel with the human genome, allowing for nearly complete cross-reference to the human genome at an average resolution of 3.5 Mb. At least 23 large-scale chromosomal rearrangements, mostly inversions, are needed to explain the changes in marker order between human and macaque. Analysis of the breakpoints flanking inverted chromosomal segments and estimation of their duplication divergence dates provide additional evidence implicating segmental duplications as a major mechanism of chromosomal rearrangement in recent primate evolution.

Animals↗
PubMed1998

A versatile image analysis approach for simultaneous chromosome identification and localization of FISH probes.

Modern cytogenetic techniques, such as comparative genomic hybridization (CGH) and the multi-color fluorescence in situ hybridization (FISH) techniques of multiplex fluorescence in situ hybridization (M-FISH) and spectral karyotyping (SKY), require a coordinated banding analysis to maximize their usefulness. All of the methods currently used, including Giemsa (G-) banding, Alu banding, and 4',6-diamidino-2-phenyl-indole (DAPI) banding, have serious drawbacks. A simple and effective method to band chromosomes concurrently with FISH is needed. To address this problem, we stained chromosomes with DAPI and chromomycin A3, and then used an image analysis program to generate banding by dividing the image taken with a DAPI excitation filter by the image taken with a chromomycin A3 excitation filter. The result was a metaphase spread in which the chromosomes possessed a banding pattern characteristic of R-banding. The image analysis program was then used to generate linescans of pixel intensity versus relative position along the length of chromosomes that were banded using this technique, which we have called D/C R-banding. Each chromosome in a genome was represented by a characteristic scan profile, which was unaffected by FISH signals. Reference linescans were prepared by karyotyping D/C R-banded chromosomes for a given species, and then drawing lines along the length of the known chromosomes. The linescans were combined into a spreadsheet database, which was linked by dynamic data exchange to the image analysis program and normalized for length and intensity. The linescan of an unknown chromosome was then transferred to the spreadsheet, where it was normalized for length and intensity and overlaid on the linescans of each chromosome in the genome. Unknown chromosomes were identified by comparison of their graphs with graphs in the standardized reference genome. We have used this approach to create reference linescan karyotypes of several species, and to identify chromosomes on which FISH was performed.

Animals↗
PubMed1994

Integrated human genome-wide maps constructed using the CEPH reference panel.

High resolution linkage maps have proven to be invaluable tools in genetic investigations. We have assembled a collection of genetic maps constructed from primary data collected from investigators performing genotyping using the Centre Etude Polymorphism Humain (CEPH) reference pedigree panel. These maps were constructed using a rigorous, semi-automated map construction algorithm that evaluates the integrity of the maps during construction. Two classes of maps were produced: a high confidence "skeletal" set composed of 544 PCR based markers, and a more highly annotated "framework" set containing maps of 1,123 markers. Genetic map locations within the framework maps are provided for an additional 1,758 loci without statistically unique interval assignments.

Algorithms↗
PubMed1999

Accessory DNA in the genomes of representatives of the Escherichia coli reference collection.

Different strains of the Escherichia coli reference collection (ECOR) differ widely in chromosomal size. To analyze the nature of the differential gene pool carried by different strains, we have followed an approach in which random amplified polymorphic DNA (RAPD) was used to generate several PCR fragments. Those present in some but not all the strains were screened by hybridization to assess their distribution throughout the ECOR collection. Thirteen fragments with various degrees of occurrence were sequenced. Three of them corresponded to RAPD markers of widespread distribution. Of these, two were housekeeping genes shown by hybridization to be present in all the E. coli strains and in Salmonella enterica LT2; the third fragment contained a paralogous copy of dnaK with widespread, but not global, distribution. The other 10 RAPD markers were found in only a few strains. However, hybridization results demonstrated that four of them were actually present in a large selection of the ECOR collection (between 42 and 97% of the strains); three of these fragments contained open reading frames associated with phages or plasmids known in E. coli K-12. The remaining six fragments were present in only between one and four strains; of these, four fragments showed no similarity to any sequence in the databases, and the other two had low but significant similarity to a protein involved in the Klebsiella capsule synthesis and to RNA helicases of archaeal genomes, respectively. Their percent GC, dinucleotide content, and codon adaptation index suggested an exogenous origin by horizontal transfer. These results can be interpreted as reflecting the presence of a large pool of strain-specific genes, whose origin could be outside the species boundaries.

Bacteriology↗
PubMed2001

RefSeq and LocusLink: NCBI gene-centered resources.

Thousands of genes have been painstakingly identified and characterized a few genes at a time. Many thousands more are being predicted by large scale cDNA and genomic sequencing projects, with levels of evidence ranging from supporting mRNA sequence and comparative genomics to computing ab initio models. This, coupled with the burgeoning scientific literature, makes it critical to have a comprehensive directory for genes and reference sequences for key genomes. The NCBI provides two resources, LocusLink and RefSeq, to meet these needs. LocusLink organizes information around genes to generate a central hub for accessing gene-specific information for fruit fly, human, mouse, rat and zebrafish. RefSeq provides reference sequence standards for genomes, transcripts and proteins; human, mouse and rat mRNA RefSeqs, and their corresponding proteins, are discussed here. Together, RefSeq and LocusLink provide a non-redundant view of genes and other loci to support research on genes and gene families, variation, gene expression and genome annotation. Additional information about LocusLink and RefSeq is available at http://www.ncbi.nlm.nih.gov/LocusLink/.

Animals↗
PubMed1993

DNA fingerprinting of renal cell carcinoma with special reference to tumor heterogeneity.

Genomic alterations in renal cell carcinoma were investigated by DNA fingerprinting using the simple repetitive oligonucleotide probe (CAC)s. Nine of ten tumors showed somatic changes in the fingerprint pattern compared with constitutional DNA. The most consistent changes were deletions and/or decrease in intensity of a band. When using two or three samples from different parts within the tumor, up to three different cell clones could be detected. These results indicate that DNA fingerprinting analysis can be a useful technique for the study of genomic alterations and tumor heterogeneity in renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed2001

Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy.

PURPOSE: Induced genomic instability generally refers to a type of damage which is transmissible down cell generations, and which results in a persistently enhanced frequency of de novo mutations, chromosomal abnormalities or lethality in a significant fraction of the descendant cell population. The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. RESULTS: The phenomenon of spontaneous genomic instability is well known in some rare genetic diseases (e.g. Gorlin's syndrome), and there is evidence in such cases that it can lead to a greater propensity for carcinogenesis (with shortened latency) which is enhanced after irradiation. It is unclear what role induced genomic instability plays in the response of normal individuals, but persistent chromosomal instability has been detected in vivo in lymphocytes and keratinocytes from irradiated normal individuals. Such induced genomic instability might play some role in tumour response in a subset of tumours with specific defects in damage response genes, but again its contribution to radiocurability in the majority of cancer patients is unclear. In normal tissues, genomic instability induced in wild-type cells leading to delayed cell death might contribute to more severe or prolonged early reactions as a consequence of increased cell loss, a longer time required for recovery, and greater residual injury. In tumours, induced genomic instability reflected in delayed reductions in clonogenic capacity might contribute to the radiosensitivity of primary tumours, and also to a lower incidence, longer latency and slower growth rate of recurrences and metastases. CONCLUSIONS: The evidence which is reviewed shows that there is little information at present to support these propositions, but what exists is consistent with their expectations. Also, it is not yet clear to what extent mutations associated with genomic instability, particularly gene polymorphisms, or other low penetrant gene mutations, contribute to the recognized spectrum of normal tissue radiosensitivity amongst cancer patients, or in the general population. Tests for such genetic modifications may help in the search for more accurate prognostic markers of response, which hopefully could be used in addition to other strategies to further improve the outcome for cancer patients given radiotherapy.

Cell Division↗
PubMedDate not supplied

Towards the physical map of the Trypanosoma cruzi nuclear genome: construction of YAC and BAC libraries of the reference clone T. cruzi CL-Brener.

Strategies to construct the physical map of the Trypanosoma cruzi nuclear genome have to capitalize on three main advantages of the parasite genome, namely (a) its small size, (b) the fact that all chromosomes can be defined, and many of them can be isolated by pulse field gel electrophoresis, and (c) the fact that simple Southern blots of electrophoretic karyotypes can be used to map sequence tagged sites and expressed sequence tags to chromosomal bands. A major drawback to cope with is the complexity of T. cruzi genetics, that hinders the construction of a comprehensive genetic map. As a first step towards physical mapping, we report the construction and partial characterization of a T. cruzi CL-Brener genomic library in yeast artificial chromosomes (YACs) that consists of 2,770 individual YACs with a mean insert size of 365 kb encompassing around 10 genomic equivalents. Two libraries in bacterial artificial chromosomes (BACs) have been constructed, BACI and BACII. Both libraries represent about three genome equivalents. A third BAC library (BAC III) is being constructed. YACs and BACs are invaluable tools for physical mapping. More generally, they have to be considered as a common resource for research in Chagas disease.

Animals↗
PubMed1994

Rapid detection of Serpulina hyodysenteriae in diagnostic specimens by PCR.

A PCR assay for the detection of Serpulina hyodysenteriae in diagnostic specimens was developed on the basis of sequence analysis of a recombinant clone designated pRED3C6. Clone pRED3C6, which contained a 2.3-kb DNA fragment unique to S. hyodysenteriae, was identified by screening a plasmid library of S. hyodysenteriae isolate B204 genomic DNA in Escherichia coli by colony immunoblot with the mouse monoclonal antibody 10G6/G10, which was produced against cell-free supernatant antigens from the same isolate. Southern blot analysis of HindIII-digested genomic DNA of S. hyodysenteriae serotypes 1 through 7 and of four weakly beta-hemolytic intestinal spirochetes, including Serpulina innocens, with the 2.3-kb DNA fragment of pRED3C6 indicated that the cloned sequence was present exclusively in the seven serotypes of S. hyodysenteriae. An oligonucleotide primer pair for PCR amplification of a 1.55-kb fragment and an internal oligonucleotide probe were designed and synthesized on the basis of sequence analysis of the 2.3-kb DNA fragment of pRED3C6. Purified genomic DNAs from reference isolates of S. hyodysenteriae serotypes 1 through 9, S. innocens, weakly beta-hemolytic intestinal spirochetes belonging to genotypic groups distinct from those of reference Serpulina spp., other cultivable reference isolates of the order Spirochaetales, and enteric bacteria including Escherichia coli, Salmonella spp., Campylobacter spp., and Bacteroides vulgatus were amplified with the oligonucleotide primer pair in a hot-start PCR. The 1.55-kb products were obtained only in the presence of genomic DNA from each of the nine serotypes of S. hyodysenteriae. The specificity of the 1.55-kb products for S. hyodysenteriae was confirmed on the basis of production of a restriction endonuclease pattern of the PCR products identical to the predicted restriction map analysis of pRED3C6 and positive hybridization signal with the S. hyodysenteriae-specific internal oligonucleotide probe. By using total DNA obtained from normal swine feces inoculated with decreasing concentrations of S. hyodysenteriae cells, the sensitivity of the PCR assay was calculated to be between 1 and 10 organisms per 0.1 g of feces. The PCR assay was 1,000 times more sensitive than conventional culture of dysenteric feces on selective medium. There was complete agreement between the results of PCR assays and anaerobic culture on selective agar medium with diagnostic specimen (n = 9) obtained from six farms on which there were cases with clinical signs suggestive of swine dysentery. Detection of S. hyodysenteriae by PCR amplification of DNA has great potential for rapid identification of S. hyodysenteriae in diagnostic specimens.

Animals↗