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At least 1,135 records · Page 63Linked to original sources
PubMed1997

The physical map of the chloroplast DNA from Korean ginseng (Panax ginseng C.A. Meyer).

To compare the gene order of the chloroplast genome among dicotyledonous plants, we constructed a physical map of chloroplast DNA (cpDNA) of Korean ginseng (Panax ginseng C.A. Meyer) with four restriction enzymes, BamHI, HindIII, EcoRI, and PstI. The restriction enzyme recognition sites of the physical map were also confirmed by Southern hybridization of total ginseng cpDNA with homologous and heterologous probes. The cpDNA of Korean ginseng was determined as a circular molecule with a total size of about 154 kb, which contain two inverted repeats of 23 kb each that disrupt the rest of the molecule into a large (90 kb) and a small single copy region (18 kb). The genome structure of Korean ginseng cpDNA was similar in size and gene order to that of tobacco cpDNA. The cpDNA of Korean and American ginseng (P. quinquefolius) showed very similar restriction patterns.

Chromosome Mapping↗
PubMed2005

Population dynamics of RNA viruses: the essential contribution of mutant spectra.

Cells and their viral and cellular parasites are genetically highly diverse, and their genomes contain signs of past and present variation and mobility. The great adaptive potential of viruses, conferred on them by high mutation rates and quasispecies dynamics, demands new strategies for viral disease prevention and control. This necessitates a more detailed knowledge of viral population structure and dynamics. Here we review studies with the important animal pathogen Foot-and-mouth disease virus (FMDV) that document modulating effects of the mutant spectra that compose viral populations. As a consequence of interactions within mutant spectra, enhanced mutagenesis may lead to viral extinction, and this is currently investigated as a new antiviral strategy, termed virus entry into error catastrophe.

Animals↗
PubMed2025

Cell-type-specific enrichment of somatic aneuploidy in the mammalian brain.

Somatic mutations alter the genomes of a subset of an individual's brain cells, impacting gene regulation and contributing to disease processes. Mosaic single-nucleotide variants have been characterized with single-cell resolution in the brain, but we have limited information about large-scale structural variation such as whole-chromosome duplication or loss. We used a dataset of over 415,000 single-cell DNA methylation and chromatin conformation profiles from the adult mouse brain to comprehensively identify and characterize aneuploid cells. Somatic trisomy events were strongly enriched on chromosome 16, which is syntenic with human chromosome 21. We also observed a specific enrichment of chromosome gain and loss events in specific cell types, including Pons neurons and oligodendrocyte precursor cells. Chromosome 16 trisomy occurred in multiple cell types and across brain regions, suggesting that nondisjunction is a recurrent feature of somatic structural variation in the brain.

Animals↗
PubMed2006

SNPeffect v2.0: a new step in investigating the molecular phenotypic effects of human non-synonymous SNPs.

UNLABELLED: Single nucleotide polymorphisms (SNPs) constitute the most fundamental type of genetic variation in human populations. About 75 000 of these reported variations cause an amino acid change in the translated protein. An important goal in genomic research is to understand how this variability affects protein function, and whether or not particular SNPs are associated to disease susceptibility. Accordingly, the SNPeffect database uses sequence- and structure-based bioinformatics tools to predict the effect of non-synonymous SNPs on the molecular phenotype of proteins. SNPeffect analyses the effect of SNPs on three categories of functional properties: (1) structural and thermodynamic properties affecting protein dynamics and stability (2) the integrity of functional and binding sites and (3) changes in posttranslational processing and cellular localization of proteins. The search interface of the database can be used to search specifically for polymorphisms that are predicted to cause a change in one of these properties. Now based on the Ensembl human databases, the SNPeffect database has been remodeled to better fit an automatically updatable structure. The current edition holds the molecular phenotype of 74 567 nsSNPs in 23 426 proteins. AVAILABILITY: SNPeffect can be accessed through http://snpeffect.vib.be.

Algorithms↗
PubMed2006

A pseudolikelihood approach for simultaneous analysis of array comparative genomic hybridizations.

DNA sequence copy number has been shown to be associated with cancer development and progression. Array-based comparative genomic hybridization (aCGH) is a recent development that seeks to identify the copy number ratio at large numbers of markers across the genome. Due to experimental and biological variations across chromosomes and hybridizations, current methods are limited to analyses of single chromosomes. We propose a more powerful approach that borrows strength across chromosomes and hybridizations. We assume a Gaussian mixture model, with a hidden Markov dependence structure and with random effects to allow for intertumoral variation, as well as intratumoral clonal variation. For ease of computation, we base estimation on a pseudolikelihood function. The method produces quantitative assessments of the likelihood of genetic alterations at each clone, along with a graphical display for simple visual interpretation. We assess the characteristics of the method through simulation studies and analysis of a brain tumor aCGH data set. We show that the pseudolikelihood approach is superior to existing methods both in detecting small regions of copy number alteration and in accurately classifying regions of change when intratumoral clonal variation is present. Software for this approach is available at http://www.biostat.harvard.edu/ approximately betensky/papers.html.

Algorithms↗
PubMed2004

Non-African populations of Drosophila melanogaster have a unique origin.

Drosophila melanogaster is widely used as a model in DNA variation studies. Patterns of polymorphism have, however, been affected by the history of this species, which is thought to have recently spread out of Africa to the rest of the world. We analyzed DNA sequence variation in 11 populations, including four continental African and seven non-African samples (including Madagascar), at four independent X-linked loci. Variation patterns at all four loci followed neutral expectations in all African populations, but departed from it in all non-African ones due to a marked haplotype dimorphism at three out of four loci. We also found that all non-African populations show the same major haplotypes, though in various frequencies. A parsimonious explanation for these observations is that all non-African populations are derived from a single ancestral population having undergone a substantial reduction of polymorphism, probably through a bottleneck. Less likely alternatives involve either selection at all four loci simultaneously (including balancing selection at three of them), or admixture between two divergent populations. Small but significant structure was observed among African populations, and there were indications of differentiation across Eurasia for non-African ones. Since population history may result in non-equilibrium variation patterns, our study confirms that the search for footprints of selection in the D. melanogaster genome must include a sufficient understanding of its history.

Africa↗
PubMed2005

Molecular characterization and chromosomal mapping of porcine adipose differentiation-related protein (ADRP).

ADRP plays an important role in regulating lipid storage in various cells. We investigated the ADRP gene as a candidate gene for intramuscular fat deposition and marbling traits in pigs. A full-length transcript of porcine ADRP was cloned by RT-PCR and RACE. The porcine ADRP cDNA (1848 bp) contains a 1377-bp open reading frame, encoding a deduced protein of 459 amino acids, which has amino acid sequence identities of 89, 89, 82 and 81% with cattle, human, mouse and rat ADRP genes respectively. The genomic structure and sequence of the porcine ADRP were also analysed using a BAC clone of a Korean native pig. Pig ADRP comprises eight exons spanning approximately 13 kb and is located on chromosome 1 q2.3-q2.7 between microsatellite markers SW2185 and SW974. Several sequence variations were detected from nine different pig breeds. The biological role of this gene and the mapping localization indicated that the porcine ADRP is a possible candidate gene for fat deposition and marbling traits.

Adipose Tissue↗
PubMed2002

Microbial aldo-keto reductases.

The aldo-keto reductases (AKR) are a superfamily of enzymes with diverse functions in the reduction of aldehydes and ketones. AKR enzymes are found in a wide range of microorganisms, and many open reading frames encoding related putative enzymes have been identified through genome sequencing projects. Established microbial members of the superfamily include the xylose reductases, 2,5-diketo-D-gluconic acid reductases and beta-keto ester reductases. The AKR enzymes share a common (alpha/beta)(8) structure, and conserved catalytic mechanism, although there is considerable variation in the substrate-binding pocket. The physiological function of many of these enzymes is unknown, but a variety of methods including gene disruptions, heterologous expression systems and expression profiling are being employed to deduce the roles of these enzymes in cell metabolism. Several microbial AKR are already being exploited in biotransformation reactions and there is potential for other novel members of this important superfamily to be identified, studied and utilized in this way.

Alcohol Oxidoreductases↗
PubMed2026

State of Cardiovascular Disease and Stroke in Hispanic/Latino Adults in the United States: A Scientific Statement From the American Heart Association.

Cardiovascular disease became the leading cause of death among Hispanic individuals in the United States in 2022. Hispanic adults experience a disproportionate burden of cardiometabolic risk factors, including obesity, diabetes, and dyslipidemia. Hispanic populations are highly heterogeneous, with substantial variations in genetic ancestry and sociocultural influences that shape cardiovascular disease risk and outcomes. The "Hispanic paradox," describing lower cardiovascular disease mortality despite higher risk factor burden, is increasingly recognized as an oversimplification that does not apply uniformly across Hispanic heritage groups, sexes, or disease types. Disaggregated data reveal substantial differences in risk profiles and disease burden among Hispanic heritage groups, emphasizing the limitations of treating this population as a monolithic unit. Recent evidence demonstrates widening disparities in hypertension control, obesity, diabetes, and metabolic diseases among Hispanic populations, threatening this prior mortality advantage. Advancing cardiovascular and equitable health will require developing a deeper understanding of the unique drivers of cardiovascular disease within diverse Hispanic communities, addressing barriers such as language and insurance access, and implementing culturally tailored interventions and policies. This scientific statement summarizes current cardiovascular disease epidemiology in Hispanic populations, emphasizing heritage group variation and social and structural determinants of health, and presents strategies to improve prevention and healthcare delivery. Key priorities for advancing cardiovascular health in Hispanic adults include expanding disaggregated data collection, increasing representation in research, and ensuring equitable implementation of precision medicine approaches, including genomics, multi-omics, and artificial intelligence, while addressing environmental exposures, psychosocial stressors, and policy-related drivers of risk in order to achieve the American Heart Association's 2028 Impact Goals to advancing health and hope for everyone, everywhere.

AHA Scientific Statements↗
PubMed1994

Development of surrogate endpoint biomarkers for clinical trials of cancer chemopreventive agents: relationships to fundamental properties of preinvasive (intraepithelial) neoplasia.

The tissue changes offering the greatest immediate potential for development as surrogate endpoint biomarkers (SEBs) to be used in Phase II trials of cancer chemopreventive agents are those derived from the microscopic tissue changes pathologists use to make the diagnosis of preinvasive (intraepithelial) neoplasia. These changes comprise four categories: proliferative index, ploidy, nuclear morphometry (size, shape, texture, and pleomorphism), and nucleolar morphometry (number, size, shape, position, and pleomorphism). Computer-assisted image analysis (CIA) permits dozens of additional morphometric parameters to be developed. Other categories of candidate SEBs are: DNA and chromosomal structural changes associated with genomic instability, activation of oncogenes and inactivation of tumor suppressor genes, structural changes in differentiated molecules, and aberrations of growth factor/receptor structure and function. Self-perpetuating DNA breakage with secondary mutator mutations in genomic stability genes is a major mechanism by which the genomic instability characteristic of neoplasia occurs, and from which stem other basic neoplastic properties, including clonal evolution, along multiple pathways of genetic variation that are stochastically determined, continuously increasing proliferation, rate and extent of phenotypic heterogeneity. SEBs resulting from genomic instability include homogeneously staining regions, double minute chromosomes, micronuclei, dicentrics, gene amplification, loss of heterozygosity, and alterations in chromosome number. Newly developed assays for detecting genomic instability include comparative genomic hybridization using fluorescence in situ hybridization on > 20 micron-thick sections monitored by confocal laser scanning microscopy, assays for microsatellite instability, and restriction landmark genomic scanning. These assays offer promise for detecting the earliest molecular changes of neoplasia in normal-appearing epithelium prior to the onset of the dysplastic phase of intraepithelial neoplasia.

Anticarcinogenic Agents↗
PubMed2005

Small RNA genes expressed from Staphylococcus aureus genomic and pathogenicity islands with specific expression among pathogenic strains.

Small RNA (sRNA) genes are expressed in all organisms, primarily as regulators of translation and message stability. We have developed comparative genomic approaches to identify sRNAs that are expressed by Staphylococcus aureus, the most common cause of hospital-acquired infections. This study represents an in-depth analysis of the RNome of a Gram-positive bacterium. A set of sRNAs candidates were identified in silico within intergenic regions, and their expression levels were monitored by using microarrays and confirmed by Northern blot hybridizations. Two sRNAs were also detected directly from purification and RNA sequence determination. In total, at least 12 sRNAs are expressed from the S. aureus genome, five from the core genome and seven from pathogenicity islands that confer virulence and antibiotic resistance. Three sRNAs are present in multiple (two to five) copies. For the sRNAs that are conserved throughout the bacterial phylogeny, their secondary structures were inferred by phylogenetic comparative methods. In vitro binding assays indicate that one sRNA encoded within a pathogenicity island is a trans-encoded antisense RNA regulating the expression of target genes at the posttranscriptional level. Some of these RNAs show large variations of expression among pathogenic strains, suggesting that they are involved in the regulation of staphylococcal virulence.

Base Pairing↗
PubMed2002

HGVbase: a human sequence variation database emphasizing data quality and a broad spectrum of data sources.

HGVbase (Human Genome Variation database; http://hgvbase.cgb.ki.se, formerly known as HGBASE) is an academic effort to provide a high quality and non-redundant database of available genomic variation data of all types, mostly comprising single nucleotide polymorphisms (SNPs). Records include neutral polymorphisms as well as disease-related mutations. Online search tools facilitate data interrogation by sequence similarity and keyword queries, and searching by genome coordinates is now being implemented. Downloads are freely available in XML, Fasta, SRS, SQL and tagged-text file formats. Each entry is presented in the context of its surrounding sequence and many records are related to neighboring human genes and affected features therein. Population allele frequencies are included wherever available. Thorough semi-automated data checking ensures internal consistency and addresses common errors in the source information. To keep pace with recent growth in the field, we have developed tools for fully automated annotation. All variants have been uniquely mapped to the draft genome sequence and are referenced to positions in EMBL/GenBank files. Data utility is enhanced by provision of genotyping assays and functional predictions. Recent data structure extensions allow the capture of haplotype and genotype information, and a new initiative (along with BiSC and HUGO-MDI) aims to create a central repository for the broad collection of clinical mutations and associated disease phenotypes of interest.

Base Sequence↗
PubMed1996

Natural isolates of ECHO virus type 25 with extensive variations in IRES sequences and different translational efficiencies.

The complete nucleotide sequence of the 5'-untranslated region (5'-UTR) of the genome of three ECHO virus type 25 strains (the JV4 reference strain and two wild isolates) was determined. The 5'-UTR of the two isolates shared 85 and 82% nucleotide identity with the reference strain. The overall folding of the predicted secondary structure of the ECHO virus 5'-UTRs showed significant conservation with that of the poliovirus. Most significant differences were observed in specific domains of the predicted IRES of the wild isolates. The efficiency with which ECHO virus type 25 5'-UTRs promoted internal initiation of translation was examined in an in vitro translation system. At low doses of input RNA, all three 5'-UTRs were similarly efficient in promoting internal ribosome entry and behaved similarly to the poliovirus IRES in that downstream cistron translation was markedly stimulated by the addition of HeLa cell extracts to standard reticulocyte lysates. At high RNA doses, the JV4 5'-UTR was much more efficient than the other two ECHO virus 5'-UTRs. This difference was much less marked when reticulocyte lysates were supplemented with 20% HeLa S-10 extracts, which suggests that the two less efficient 5'-UTRs were characterized by a reduced binding capacity to at least one factor present in HeLa cells. In MRC5 cell S-10 extract, internal initiation of translation was stimulated from the IRES of all three ECHO strains, the M1262 IRES being the least stimulated.

Base Sequence↗
PubMed2001

A chromosomal region surrounding the ompD porin gene marks a genetic difference between Salmonella typhi and the majority of Salmonella serovars.

In this work it is shown that the majority of Salmonella serovars most frequently associated with the systemic infection of vertebrate hosts produce a major outer-membrane porin, OmpD. However, OmpD is absent from the outer-membrane protein profiles of Salmonella typhi strain Ty2 and 26 clinical isolates of S. typhi examined by SDS-PAGE. To determine whether the ompD gene is present in S. typhi, primers internal to the ompD coding sequence were used to amplify the gene by PCR. With the exception of S. typhi strains, the ompD gene was amplified from the genomes of all Salmonella serovars tested. Consistently, a specific ompD probe did not hybridize with DNA isolated from the S. typhi strains. Taken together, these results demonstrate that S. typhi does not produce OmpD due to the absence of the ompD gene. Furthermore, it was investigated whether the deletion of ompD extended to smvA. This gene is adjacent to ompD in the Salmonella typhimurium chromosome and encodes a protein involved in the resistance to methyl viologen, a superoxide-generating agent. Although PCR failed to amplify the smvA gene from the S. typhi strain Ty2 genome, it was possible to amplify it from the chromosome of the clinical strains. On the other hand, hybridization analyses showed that the smvA gene is present in all the S. typhi strains tested. In contrast to the other Salmonella serovars, S. typhi strain Ty2 and the clinical isolates showed sensitivity to methyl viologen, suggesting that smvA gene is inactive in S. typhi. In conclusion, the ompD-smvA region is variable in structure among Salmonella serovars. It is hypothesized that the absence of ompD may suggest a role in host specificity.

Bacterial Proteins↗
PubMed2003

A note on genetic variance components in mixed models.

Burton et al. ([1999] Genet. Epidemiol. 17:118-140) proposed a series of generalized linear mixed models for pedigree data that account for residual correlation between related individuals. These models may be fitted using Markov chain Monte Carlo methods, but the posterior mean for small variance components can exhibit marked positive bias. Burton et al. ([1999] Genet. Epidemiol. 17:118-140) suggested that this problem could be overcome by allowing the variance components to take negative values. We examine this idea in depth, and show that it can be interpreted as a computational device for locating the posterior mode without necessarily implying that the original random effects structure is incorrect. We illustrate the application of this technique to mixed models for familial data.

Data Interpretation, Statistical↗
PubMed1998

Tam3 in Antirrhinum majus is exceptional transposon in resistant to alteration by abortive gap repair: identification of nested transposons.

Most transposon families consist of heterogeneous copies with varying sizes. In contrast, the Tam3 copies in Antirrhinum majus are known to have exceptionally conserved structures of uniform size. Gap repair has been reported to be involved in the structural alteration of copies from several transposon families. In this study, we have asked whether or not gap repair has affected Tam3 copies. Five Tam3 copies carrying aberrant sequences were selected from 40 independent Tam3 clones and their sequences were analyzed. Two of the five copies contain insertions in the Tam3 sequence. These two insertions, designated Tam356 and Tam661, are typical transposon-like sequences, which have terminal inverted repeats and cause target site duplication. These nested transposons were obviously associated with transpositional events, and did not originate from the gap-repair process. The remaining three copies had lost large parts of the Tam3 sequence. We could not find any relationship between the deletions of Tam3 sequence in the three copies and gap repair. PCR analysis of a Tam3 excision site in the nivea(recurrence:Tam3) mutant also showed that most of the repair events after the Tam3 excision involved end-joining. In addition to the results obtained here, among the other clones isolated, we could not find any of the internally deleted copies that comprise a major part of other transposon families. All of these data suggest that some feature of the Tam3 structure suppresses the structural alterations that are otherwise generated during the gap repair process.

Alleles↗
PubMed2004

CYP3A variation and the evolution of salt-sensitivity variants.

Members of the cytochrome P450 3A subfamily catalyze the metabolism of endogenous substrates, environmental carcinogens, and clinically important exogenous compounds, such as prescription drugs and therapeutic agents. In particular, the CYP3A4 and CYP3A5 genes play an especially important role in pharmacogenetics, since they metabolize >50% of the drugs on the market. However, known genetic variants at these two loci are not sufficient to account for the observed phenotypic variability in drug response. We used a comparative genomics approach to identify conserved coding and noncoding regions at these genes and resequenced them in three ethnically diverse human populations. We show that remarkable interpopulation differences exist with regard to frequency spectrum and haplotype structure. The non-African samples are characterized by a marked excess of rare variants and the presence of a homogeneous group of long-range haplotypes at high frequency. The CYP3A5*1/*3 polymorphism, which is likely to influence salt and water retention and risk for salt-sensitive hypertension, was genotyped in >1,000 individuals from 52 worldwide population samples. The results reveal an unusual geographic pattern whereby the CYP3A5*3 frequency shows extreme variation across human populations and is significantly correlated with distance from the equator. Furthermore, we show that an unlinked variant, AGT M235T, previously implicated in hypertension and pre-eclampsia, exhibits a similar geographic distribution and is significantly correlated in frequency with CYP3A5*1/*3. Taken together, these results suggest that variants that influence salt homeostasis were the targets of a shared selective pressure that resulted from an environmental variable correlated with latitude.

Black or African American↗
PubMed2000

Virtually full-length subtype F and F/D recombinant HIV-1 from Africa and South America.

For reliable classification of HIV-1 strains appropriate reference sequences are needed. The HIV-1 genetic subtype F has a wide geographic spread, causing significant epidemics in South America, Africa, and some regions of Europe. Previously only two full-length sequences of each of the HIV-1 subtype F subclusters F1 and F2 have been described. To extend the knowledge of subtype F variation on a complete genome level, three new virtually full-length F1 sequences were cloned and sequenced, two from Africa and one from South America. Comparison of the new and previously described sequences showed that monophyletic clustering of the subcluster F1 of subtype F is consistent and highly supported in all genome regions. Two additional full-length strains were shown to be mosaics of subtypes F and D. These epidemiologically unrelated F/D sequences showed similar chimeric structure, suggesting that they may represent a previously undescribed circulating recombinant form (CRF). This was supported by partial sequences from three additional unlinked F/D recombinants. Genetic distances in the phylogenetic trees suggest that the recombination event leading to the putative CRF occurred relatively long ago, close to the divergence of the F1 and F2 subclusters. Furthermore, all five F/D recombinants are linked to the Democratic Republic of Congo, suggesting that the original recombination event took place in central Africa.

Africa↗