Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “repetitive elements”

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 973 records · Page 54Linked to original sources

Linker histone-DNA complexes: enhanced stability in the presence of aluminum lactate and implications for Alzheimer's disease.

The binding of human brain linker histone proteins to a radiolabelled human Alu repetitive element was examined by mobility shift assay. Analysis of the complexes formed from protein extracts of whole neocortical nuclei, under physiological conditions in vitro revealed that linker histone H1(0) has the highest affinity for the Alu DNA sequence. The linker histone-DNA complexes assembled in the presence of aluminum lactate were more resistant to sodium chloride-induced dissociation than those formed in the presence of sodium lactate. The enhanced stability of deoxyribonucleoprotein (DNP) complexes in the presence of the aluminum cation may be of significance in neurodegenerative conditions such as Alzheimer's disease where aluminum preferentially associates with DNA containing structures of the nucleus.

Alzheimer Disease↗

Association between divergence and interspersed repeats in mammalian noncoding genomic DNA.

The amount of noncoding genomic DNA sequence that aligns between human and mouse varies substantially in different regions of their genomes, and the amount of repetitive DNA also varies. In this report, we show that divergence in noncoding nonrepetitive DNA is strongly correlated with the amount of repetitive DNA in a region. We investigated aligned DNA in four large genomic regions with finished human sequence and almost or completely finished mouse sequence. These regions, totaling 5.89 Mb of DNA, are on different chromosomes and vary in their base composition. An analysis based on sliding windows of 10 kb shows that the fraction of aligned noncoding nonrepetitive DNA and the fraction of repetitive DNA are negatively correlated, both at the level of an entire region and locally within it. This conclusion is strongly supported by a randomization study, in which repetitive elements are removed and randomly relocated along the sequences. Thus, regions of noncoding genomic DNA that accumulated fewer point mutations since the primate-rodent divergence also suffered fewer retrotransposition events. These results indicate that some regions of the genome are more "flexible" over the time scale of mammalian evolution, being able to accommodate many point mutations and insertions, whereas other regions are more "rigid" and accumulate fewer changes. Stronger conservation is generally interpreted as indicating more extensive or more important function. The evidence presented here of correlated variation in the rates of different evolutionary processes across noncoding DNA must be considered in assessing such conservation for evidence of selection.

Animals↗

Synthetic DNA probes for the identification of sibling species in the Anopheles gambiae complex.

The cloned DNA sequences pAna1, pAnq1 and pAnm14, which may be used to distinguish between at least five of the six species in the Anopheles gambiae Giles complex of Afrotropical malaria vector mosquitoes, have been sequenced. Each clone was found to possess a series of repeated sequences of 41, 30 and 163 bases respectively. In pAnq1 and pAnm14 the repeats were in direct tandem array, whilst in pAna1 the repetitive sequence was found to be interspersed by 15-17 variable bases. A comparison of a number of copies of each of the repetitive sequences within the three clones enabled the definition of the consensus sequence for each repetitive element. Based on these consensus sequences, three oligonucleotides of 21, 23 and 26 bases were derived from pAna1, pAnq1 and pAnm14 respectively. When tested as probes against DNA dot-blots and squash-blots of mosquito specimens, each oligonucleotide retained the same species-specificity as the original clones from which they were derived. The radioactively labelled oligonucleotides were able to detect as little as 5 ng of target genomic DNA in an overnight autoradiographic exposure. The synthetic DNA probes will form the basis of a simplified system for the field identification of Anopheles gambiae sibling species specimens.

Animals↗

[Bacterial genotyping in nosocomial infections].

Hospitalized patients are at unusually high risk of infections, and furthermore, the hospital environment favors the acquisition of resistance to antimicrobial agents, complicating the treatment of nosocomial infections due to drug-resistant pathogens. The prevention of nosocomial infections, based on a surveillance system as an essential element of an infection control program, is the only way to reduce morbidity and mortality. A typing method for strain clonality permits the infection control program to confirm the association between infected patients and the reservoir for the microorganisms of interest and to determine modes of transmission, because the mode of transmission or reservoir may not be the same for multiple strains of a bacterial species. An ideal method of subtyping bacterial isolates from a given species should be simple, rapid, sensitive and discriminatory. Traditionally, once bacterial isolates from an outbreak have been determined to be of the same species, further evaluation for similarity or relatedness has been based on phenotypic methods. Biotyping, serotyping, phagetyping, and antibiotype determination are not always adequately sensitive to distinguish unrelated strains with similar phenotypes. Within phenotypic methods, multilocus enzyme electrophoresis is a powerful tool but because of its complexity it is not likely to become widely available for study of local outbreaks of bacterial infections. In recent years, molecular genetic methods, including plasmid profile, genomic restriction fragment length polymorphism analyses by conventional electrophoresis or by pulsed-field gel electrophoresis, single chromosomal gene polymorphism by DNA hybridization or by PCR amplification, ribotyping, and genomic fingerprinting generated by repetitive element sequence-based polymerase chain reaction, have been useful in evaluating endemic infections and outbreaks of a variety of nosocomial pathogens. For epidemiologic studies, genotyping systems based on defined chromosomal genes or whole DNA polymorphism provide significant advantages over plasmid analysis. Among plasmid-non-based genotypic methods, the choice depends on i) the examination of how much discrimination the method can add for the epidemiologic investigation, ii) the resources available to the laboratory, and iii) the level of expertise of the personnel involved in the testing because, until standardized rules of interpretation are published, the same data may be interpreted in different ways by different investigators. Finally, biotyping, serotyping, and antibiotype determination remain an appropriate first step for the evaluation of apparent outbreaks with the caveat that different strains with the same phenotypic properties may exist concurrently within the same environment. Genotyping may be a second level of analysis to evaluate relatedness of bacterial strains, because the use of molecular biology techniques should support an epidemiologic investigation rather than initiate it.

Bacterial Typing Techniques↗

Regulation of RNA polymerase III transcription in response to Simian virus 40 transformation.

Transcription by RNA polymerase III of the B2 family of middle-repetitive elements is activated in response to transformation by a variety of agents, including DNA tumour viruses, RNA tumour viruses and chemical carcinogens. We have investigated the mechanism of activation in SV40-transformed cells and we find that the effect is due to an increase in the activity of the general class III transcription factor TFIIIC, achieved both by an increase in factor abundance and by a change in its phosphorylation state. SV40 transformation also stimulates transcription of other genes by RNA polymerase III but the effect may be balanced by compensatory post-transcriptional changes. TFIIIC may mediate the stimulation of polymerase III transcription by a range of transforming viruses.

Animals↗

Evolutionary diversity and potential recombinogenic role of integration targets of Non-LTR retrotransposons.

Short interspersed elements (SINEs) make up a significant fraction of total DNA in mammalian genomes, providing a rich substrate for chromosomal rearrangements by SINE-SINE recombinations. Proliferation of mammalian SINEs is mediated primarily by long interspersed element 1 (L1) non-long terminal repeat retrotransposons that preferentially integrate at DNA sequence targets with an average length of approximately 15 bp and containing conserved endonucleolytic nicking signals at both ends. We report that sequence variations in the first of the two nicking signals, represented by a 5'-TT-AAAA consensus sequence, affect the position of the second signal thus leading to target site duplications (TSDs) of different lengths. The length distribution of TSDs appears to be affected also by L1-encoded enzyme variants because targets with the same 5' nicking site can be of different average lengths in different mammalian species. Taking this into account, we reanalyzed the second nicking site and found that it is larger and includes more conserved sites than previously appreciated, with a consensus of 5'-ANTNTN-AA. We also studied potential involvement of the nicking sites in stimulating recombinations between SINEs. We determined that SINEs retaining TSDs with perfect 5'-TT-AAAA nicking sites appear to be lost relatively rapidly from the human and rat genomes and less rapidly from dog. We speculate that the introduction of DNA breaks induced by recurring endonucleolytic attacks at these sites, combined with the ubiquitousness of SINEs, may significantly promote recombination between repetitive elements, leading to the observed losses. At the same time, new L1 subfamilies may be selected for "incompatibility" with preexisting targets. This provides a possible driving force for the continual emergence of new L1 subfamilies which, in turn, may affect selection of L1-dependent SINE subfamilies.

Animals↗

Selective Differential Display of RNAs containing interspersed repeats: analysis of changes in the transcription of HERV-K LTRs in germ cell tumors.

A technique for the Selective Differential Display of RNAs containing Interspersed Repeats (SDDIR) has been elaborated. SDDIR involves two main steps: (1) selective amplification by RT-PCR of a subset of the total cellular RNA containing a certain type of repetitive element, and (2) side-by-side display of the amplicons derived from the tissues under comparison by means of gel electrophoresis in parallel lanes. The technique was used to compare the expression of transcripts containing LTR (Long Terminal Repeat) sequences derived from human endogenous retrovirus K (HERV-K) in testicular germ cell tumors and in corresponding normal tissue. SDDIR enabled us to obtain an overview of LTRs represented in the total transcribed fraction and to reveal differences in transcription patterns of the LTRs in normal and tumor tissues. An unexpectedly large number of LTRs was found to be transcribed, and the levels of many of the transcripts differed between normal and tumor tissues.

Base Sequence↗

A technique for genome-wide identification of differences in the interspersed repeats integrations between closely related genomes and its application to detection of human-specific integrations of HERV-K LTRs.

We have developed a method of targeted genomic difference analysis (TGDA) for genomewide detection of interspersed repeat integration site differences between closely related genomes. The method includes a whole-genome amplification of the flanks adjacent to target interspersed repetitive elements in both genomic DNAs under comparison, and subtractive hybridization (SH) of the selected amplicons. The potential of TGDA was demonstrated by the detection of differences in the integration sites of human endogenous retroviruses K (HERV-K) and related solitary long terminal repeats (LTRs) between the human and chimpanzee genomes. Of 55 randomly sequenced clones from a library enriched with human-specific integration (HSI) sites, 33 (60%) represented HSIs. All the human-specific (Hs) LTRs belong to two related evolutionarily young groups, suggesting simultaneous activity of two master genes in the hominid lineage. No deletion/insertion polymorphism was detected for the LTR HSIs for 25 unrelated caucasoid individuals. We also discuss the possible research applications for TGDA research.

Animals↗

Hydroxymethylbilane synthase: complete genomic sequence and amplifiable polymorphisms in the human gene.

Acute intermittent porphyria (AIP), an autosomal dominant inborn error of heme biosynthesis, results from the half-normal activity of the heme biosynthetic enzyme hydroxymethylbilane synthase (HMB-synthase). Heterozygous individuals are prone to life-threatening acute neurologic attacks, which are precipitated by certain drugs and other metabolic, hormonal, and nutritional factors. Since the biochemical diagnosis of heterozygous individuals has been problematic, recent efforts have focused on the identification of mutations and diagnostically useful restriction fragment length polymorphisms (RFLPs) in the HMB-synthase gene. To facilitate these endeavors, the human HMB-synthase gene, including 1.1 kg of the 5' flanking region, was isolated and completely sequenced in both orientations. The 10,024-bp gene contained 15 exons ranging in size from 39 to 438 bp and 14 introns ranging from 87 to 2913 bp. All intron/exon boundaries conformed to the GT/AG consensus rule. There were six Alu repetitive elements, one of the J and five of the Sa subfamilies. Analysis of the 1.1-kb 5' flanking region revealed putative regulatory elements for the housekeeping promoter including AP1, AP4, SP1, TRE, ENH, and CAC. This region contained 10 HpaII sites and had an overall GC content of 54%. Intron 1, which contained the erythroid-specific promoter, had putative regulatory motifs for NF-1, NF-E1, NF-E1(b), NF-E2, AP1, AP4, TOPO, CAAC, CAC, CAAT, and TATA. The locations and variant nucleotides for the known RFLPs in intron 1 were identified [MspI, nucleotide 1345 G/A; PstI, 1500 C/T; ApaLI, 2377 C/A; and BstNI, 2479 G/A] and improved polymerase chain reaction (PCR)-based detection methods for each were established.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

Two highly reiterated nucleotide sequences in the low C-value genome of Panagrellus redivivus.

Two families of highly reiterated satellite nucleotide (nt) sequences have been found in the genome of the sexually separated nematode Panagrellus redivivus. The repeats are arranged in tandem arrays but the different satellites are not intermingled. Monomeric lengths are of 155 bp for one kind and 167 bp for the other; they were named E155 and E167. The A + T content is elevated in both families (i.e., 59.5%, and 65.3%, respectively). No similarity was found between the two satellites nor to other known highly repetitive elements. Furthermore, nt methylation as well as transcriptional activity were negative. An internal subrepeating unit, about 30 bp long, was observed in E167, implying that it could have evolved from a shorter sequence. Reiteration frequencies are approx. 30,000 and 40,000 copies per haploid genome, for E155 and E167, respectively, constituting together about 17% of the total DNA. This figure is astonishingly high, considering a C-value of 70,000 kb in P. redivivus, which is thought to be the lower limit for metazoans. Hence, the genome complexity is approx. 58,000 kb. In contrast to the nematodes Ascaris lumbricoides and Parascaris equorum, however, P. redivivus does not seem to eliminate large blocks of satellite DNA in the presomatic cells during early development.

Animals↗

Long interspersed L1 repeats in rabbit DNA are homologous to L1 repeats of rodents and primates in an open-reading-frame region.

Determination of the DNA sequence of a cluster of repetitive elements located 3' to the rabbit beta-1 globin gene shows that previously identified B, E, and D repeats are linked to form a long repeat. The B and E regions are homologous to the L1 long interspersed repeats of primates and rodents. Thus L1 repeats are widely dispersed in several different mammalian orders. The sequence similarity among L1 repeats from three species is limited to a long segment that contains extensive open reading frames. This conserved region is followed by a highly divergent segment that corresponds to a 3' untranslated region. The conservation of sequences in the open-reading-frame region coupled with the divergence of the untranslated region supports the hypothesis that the L1 repeats are derived from transcripts of a functional gene that encodes a protein.

Animals↗

Evidence for lateral transfer to Brucellae: characterization of a locus with a Tn-like element (Tn2020).

A genomic locus was discovered within Brucella abortus that contains a novel transposon-like element designated Tn2020. Tn2020 is bounded by a copy of an insertion sequence designated IS2020 and a truncated imperfect copy of IS2020 (tIS2020A). The truncated copy is immediately adjacent to a second copy of IS2020. These data are consistent with the locus having evolved by a complex rearrangement following the transposition of a second copy of Tn2020. Analysis of the organization, orientation, and open reading frames (ORFs) of IS2020 places it within the IS6 family. Four ORFs from Tn2020 were translated in vitro producing a potential transposase with an apparent molecular mass of 27.5 kDa, and three polypeptides with apparent molecular masses of 71 kDa, 22 kDa, and 14 kDa. The central region of Tn2020 encodes the 71 kDa and 14 kDa proteins, while the 22 kDa protein is likely an internal translation initiation product of the IS2020 transposase. The 71 kDa protein shares sequence similarity with several bacterial transcriptional regulatory proteins and may form a helix-turn-helix structure capable of binding DNA. No homologous protein sequences to the 14 kDa peptide were detected in available databases. The 27.5 kDa transposase and its 22 kDa internal translation product shared significant similarity to several transposases from diverse bacterial hosts. Immediately 5' of Tn2020 are genes encoding ribosomal proteins RplU and RpmA. This region also contains a 90 bp sequence that shares significant homology to a repetitive element with inverted repeats from the Sinorhizobium genome. Downstream from Tn2020 is an ORF encoding a protein having significant similarity to a hypothetical protein from Caulobacter. The locus is lower in G+C content from that of the genome. These data suggest that lateral transfer of genetic material has occurred.

Amino Acid Sequence↗

Comparative architectural aspects of regions of conserved synteny on human chromosome 11p15.3 and mouse chromosome 7 (including genes WEE1 and LMO1).

Human chromosome 11p15.3 is associated with chromosome aberrations in the Beckwith Wiedemann Syndrome and implicated in the pathogenesis of different tumor types including lung cancer and leukemias. To date, only single tumor-relevant genes with linkage to this region (e.g. LMO1) have been found suggesting that this region may harbor additional potential disease associated genes. Although this genomic area has been studied for years, the exact order of genes/chromosome markers between D11S572 and the WEE1 gene locus remained unclear. Using the FISH technique and PAC clones of the flanking markers we determined the order of the genomic markers. Based on these clones we established a PAC contig of the respective region. To analyse the chromosome area in detail the synteny of the orthologous region on distal mouse chromosome 7 was determined and a corresponding mouse clone contig established, proving the conserved order of the genes and markers in both species: "cen-WEE1-D11S2043-ZNF143-RANBP7-CEGF1- ST5-D11S932-LMO1-D11S572-TUB-tel", with inverted order of the murine genes with respect to the telomere/centromere orientation. The region covered by these contigs comprises roughly 1.6 MB in human as well as in mouse. The genomic sequence of the two subregions (around WEE1 and LMO1) in both species was determined using a shotgun sequencing strategy. Comparative sequence analysis techniques demonstrate that the content of repetitive elements seems to decline from centromere to telomere (52.6% to 34.5%) in human and in the corresponding murine region from telomere to centromere (41.87% to 27.82%). Genomic organisation of the regions around WEE1 and LMO1 was conserved, although the length of gene regions varied between the species in an unpredictable ratio. CpG islands were found conserved in putative promoter regions of the known genes but also in regions which so far have not been described as harboring expressed sequences.

AT Rich Sequence↗

The human homogentisate 1,2-dioxygenase (HGO) gene.

Alkaptonuria (AKU; McKusick No. 203500), a rare hereditary disorder of the phenylalanine catabolism, was the first disease to be interpreted as an inborn error of metabolism (A. E. Garrod, 1902, Lancet 2: 1616-1620). AKU patients are deficient for homogentisate 1,2-dioxygenase (HGO; EC 1.13.11.5). This enzymatic deficiency causes homogentisic aciduria, ochronosis, and arthritis. Recently we cloned the human HGO gene and showed that AKU patients carry two copies of a loss-of-function HGO allele. Here we describe the complete nucleotide sequence of the human HGO gene and the identification of its promoter region. The human HGO gene spans 54,363 bp and codes for a 1715-nt-long transcript that is split into 14 exons ranging from 35 to 360 bp. The HGO introns, 605 to 17,687 bp in length, contain representatives of the major classes of repetitive elements, including several simple sequence repeats (SSR). Two of these SSRs, a (CT)n repeat in intron 4 and a (CA)n repeat in intron 13, were found to be polymorphic in a Spanish population sample. The HGO transcription start site was determined by primer extension. We report that sequences from -1074 to +89 bp (relative to the HGO transcription start site) are sufficient to promote transcription of a CAT reporter gene in human liver cells and that this fragment contains putative binding sites for liver-enriched transcription factors that might be involved in the regulation of HGO expression in liver.

Alkaptonuria↗

Specific transcripts are elevated in Saccharomyces cerevisiae in response to DNA damage.

Differential hybridization has been used to identify genes in Saccharomyces cerevisiae displaying increased transcript levels after treatment of cells with UV irradiation or with the mutagen/carcinogen 4-nitroquinoline-1-oxide (NQO). We describe the isolation and characterization of four DNA damage responsive genes obtained from screening ca. 9,000 yeast genomic clones. Two of these clones, lambda 78A and pBR178C, contain repetitive elements in the yeast genome as shown by Southern hybridization analysis. Although the genomic hybridization pattern is distinct for each of these two clones, both of these sequences hybridize to large polyadenylated transcripts ca. 5 kilobases in length. Two other DNA damage responsive sequences, pBRA2 and pBR3016B, are single-copy genes and hybridize to 0.5- and 3.2-kilobase transcripts, respectively. Kinetic analysis of the 0.5-kilobase transcript homologous to pBRA2 indicates that the level of this RNA increases more than 15-fold within 20 min after exposure to 4-nitroquinoline-1-oxide. Moreover, the level of this transcript is significantly elevated in cells containing the rad52-1 mutation which are deficient in DNA strand break repair and gene conversion. These results provide some of the first evidence that DNA damage stimulates transcription of specific genes in eucaryotic cells.

4-Nitroquinoline-1-oxide↗

Structure of DNA near long tandem arrays of alpha satellite DNA at the centromere of human chromosome 7.

The centromeric regions of human chromosomes contain long tracts of tandemly repeated DNA, of which the most extensively characterized is alpha satellite. In a screen for additional centromeric DNA sequences, four phage clones were obtained which contain alpha satellite as well as other sequences not usually found associated with tandemly repeated alpha satellite DNA, including L1 repetitive elements, an Alu element, and a novel AT-rich repeated sequence. The alpha satellite DNA contained within these clones does not demonstrate the higher-order repeat structure typical of tandemly repeated alpha satellite. Two of the clones contain inversions; instead of the usual head-to-tail arrangement of alpha satellite monomers, the direction of the monomers changes partway through each clone. The presence of both inversions was confirmed in human genomic DNA by polymerase chain reaction amplification of the inverted regions. One phage clone contains a junction between alpha satellite DNA and a novel low-copy repeated sequence. The junction between the two types of DNA is abrupt and the junction sequence is characterized by the presence of runs of A's and T's, yielding an overall base composition of 65% AT with local areas > 80% AT. The AT-rich sequence is found in multiple copies on chromosome 7 and homologous sequences are found in (peri)centromeric locations on other human chromosomes, including chromosomes 1, 2, and 16. As such, the AT-rich sequence adjacent to alpha satellite DNA provides a tool for the further study of the DNA from this region of the chromosome. The phage clones examined are located within the same 3.3-Mb SstII restriction fragment on chromosome 7 as the two previously described alpha satellite arrays, D7Z1 and D7Z2. These new clones demonstrate that centromeric repetitive DNA, at least on chromosome 7, may be more heterogeneous in composition and organization than had previously been thought.

Animals↗

Genomic instability in Schistosoma mansoni.

In schistosomes, the W chromosome characterizes the heterogametic female-sex (ZW) whereas males are homogametic (ZZ). In the heterochromatic region of the W chromosome, the repetitive elements W1 and W2 are located which had originally been found as female-specific sequences in Puerto Rican isolates of Schistosoma mansoni. An analysis of the strain- and sex-specific occurrence of these elements revealed that both elements can occur gender-independently in other Puerto Rican isolates and in a variety of other strains of S. mansoni. This result contradicted earlier findings and indicated the existence of polymorphic Z chromosomes. A genetic analysis of the occurrence of W1 and W2 in a series of clonal populations of Schistsoma mansoni is presented. Although clones of this parasite are regarded as genetically identical, striking inter- and even intra-clonal variations have been found by PCR and Southern-blot experiments with the DNA of individual clones and of the progeny of crossing experiments. The results do not support the hypothesis of polymorphic Z chromosomes. Instead, they strongly suggest genomic instability probably originating from unusual DNA recombination events at the meiotic and mitotic level. These findings suggest a further method of generating variability within schistosomes. rights reserved.

Animals↗

Triplet repeats in clinical subtypes of schizophrenia: variation at the DRPLA (B 37 CAG repeat) locus is not associated with periodic catatonia.

Clinical evidence for a dominant mode of inheritance and anticipation in periodic catatonia, a distinct subtype of schizophrenia, indicates that genes with triplet repeat expansions or other unstable repetitive elements affecting gene expression may be involved in the etiology of this disorder. Because patients affected with dentatorubral-pallidoluysian atrophy (DRPLA) may present with "schizophrenic" symptoms, we have investigated the DRPLA (B 37 CAG repeat) locus on chromosome 12 in 41 patients with periodic catatonia. The B 37 CAG repeat locus was highly polymorphic but all alleles in both the patient and control group had repeat sizes within the normal range. We conclude that variation at the DRPLA locus is unlikely to be associated with periodic catatonia. The evidence for dominant inheritance and anticipation as well as the high prevalence of human brain genes containing trinucleotide repeats justifies further screening for triplet repeat expansions in periodic catatonia.

Adult↗