SEARCH · PubMed Health

Results for “Interspersed Repetitive Sequences”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 613 records · Page 34Linked to original sources

PubMed1990

Selective cloning and sequence analysis of the human L1 (LINE-1) sequences which transposed in the relatively recent past.

L1 (LINE-1), a long interspersed repetitive DNA family of mammalian genomes, is thought to be a sequence family derived from a retrotransposon-like element(s), but its actively transposable unit(s) has not been identified yet. We developed a novel method for selective isolation of the human L1 sequences which transposed in a relatively recent past and may have still retained a feature of the 'active L1' unit. From the inspection of the nucleotide sequences, we conjectured that the 'active L1' or 'nearly active L1' units should have a high content of the CpG dinucleotide sequence, a mutation hot spot sequence, and contain several sites for rare cutters such as BssH II and Nar I at their 5' terminal regions. Using these rare cutter sites as selection markers, the L1 sequences were isolated, which had the high content of CpG at the 5' terminal regions and over 90% homology to L1 transcripts found in a human teratocarcinoma cell line. These L1s were shown to be 'relatively new L1' units which had integrated into chromosomes within these several million years during evolution. From the sequence data of these L1s and L1 cDNA, a consensus sequence of the 5' terminal region of high CpG L1s were constructed. A region of the consensus sequence showed about 69% homology to the 5' terminal region of Drosophila jockey element.

Animals↗

PubMed1995

Evolution of the active sequences of the HpaI short interspersed elements.

Ninety-nine members of the salmonid HpaI and AvaIII families of short interspersed repetitive elements (SINEs) were aligned and a general consensus sequence was deduced. The presence of 26 correlated changes in nucleotides (diagnostic nucleotides) from those in the consensus sequence allowed us to divide the members of the HpaI family into 12 subfamilies and those of the AvaIII family into two subfamilies. On the basis of the average sequence divergences and the phylogenetic distributions of the subfamilies, the relative antiquity of the subfamilies and the process of sequential changes in the respective source sequences were inferred. Despite the higher mutation rates of CG dinucleotides in individual dispersed members, no hypermutability of CG positions was observed in changes in the source sequences. This result suggests that sequences of SINEs located in a nonmethylated or hypomethylated genomic region could have been selected as source sequences for retroposition and/or that some CG sites are the parts of recognition sequences of retropositional machineries.

Animals↗

PubMed1979

[Distribution and enzymic hypermethylation of inverted DNA repeats in different murine and human cells (author's transl)].

A specific class of DNA sequences, the inverted repetitive sequences, forms a double-stranded structure within a single linear polynucleotide chain in denatured DNA. The reassociation process is unimolecular and occurs very fast. Quantitative analyses have shown that these sequences comprise about 4--5% of the nuclear DNA of various mammalian cells (P815 mouse mastocytoma, Hela, L cells, Raji and Chang cells, and human embryonic hepatocytes) and are interspersed within sequences of other degrees of repetitiveness. After labeling the cells with L-[Methyl-3H]methionine and [14C]deoxycytidine, relative rates of enzymic DNA methylation were computed on the basis of 3H and 14C radioactivities found in pyrimidine residues of the nuclear DNA. The results indicate that DNA of inverted repetitive sequences is methylated to a level about 50% higher than the ordinary repetitive sequences and to about 300% higher than the unique and intermediary sequences. The biological function of the inverted repeats as well as the role of their enzymic hypermethylation is unknown.

Animals↗

PubMed2006

Asymptotically increasing compliance of genomes with Chargaff's second parity rules through inversions and inverted transpositions.

Chargaff's second parity rules for mononucleotides and oligonucleotides (CIImono and CIIoligo rules) state that a sufficiently long (> 100 kb) strand of genomic DNA that contains N copies of a mono- or oligonucleotide, also contains N copies of its reverse complementary mono- or oligonucleotide on the same strand. There is very strong support in the literature for the validity of the rules in coding and noncoding regions, especially for the CIImono rule. Because the experimental support for the CIIoligo rule is much less complete, the present article, focusing on the special case of trinucleotides (triplets), examined several gigabases of genome sequences from a wide range of species and kingdoms including organelles such as mitochondria and chloroplasts. I found that all genomes, with the only exception of certain mitochondria, complied with the CIItriplet rule at a very high level of accuracy in coding and noncoding regions alike. Based on the growing evidence that genomes may contain up to millions of copies of interspersed repetitive elements, I propose in this article a quantitative formulation of the hypothesis that inversions and inverted transposition could be a major contributing if not dominant factor in the almost universal validity of the rules.

Animals↗

PubMed2000

Skeletal muscle titin: physiology and pathophysiology.

Titins are a family of gigantic filamentous muscle proteins essential for muscle structure, function and development. Most of their sequence consists of repetitive modules of two superfamily motifs, immunoglobulin and fibronectin, interspersed with unique sequences. A special feature is that many regions are differentially expressed in different muscle types, providing unique characteristics. Titin is evolutionarily old, and many regions are highly conserved. Most mutations that alter titin's characteristics seem to be incompatible with life, since very few associated genetic diseases have been described. The autoimmune response against titin in the paraneoplastic form of myasthenia gravis is discussed.

Animals↗

PubMed2006

Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Unusual evolution of interspersed repeat sequences in the Drosophila ananassae subgroup.

New repeat sequences were found in the Drosophila ananassae genome sequence. They accounted for approximately 1.2% of the D. ananassae genome and were estimated to be more abundant in genomes of its closely related species belonging to the Drosophila bipectinata complex, whereas it was entirely absent in the Drosophila melanogaster genome. They were interspersed throughout euchromatic regions of the genome, usually as short tandem arrays of unit sequences, which were mostly 175-200 bp long with two distinct peaks at 180 and 189 bp in the length distribution. The nucleotide differences among unit sequences within the same array (locus) were much smaller than those between separate loci, suggesting within-locus concerted evolution. The phylogenetic tree of the repeat sequences from different loci showed that divergences between sequences from different chromosome arms occurred only at earlier stages of evolution, while those within the same chromosome arm occurred thereafter, resulting in the increase in copy number. We found RNA polymerase III promoter sequences (A box and B box), which play a critical role in retroposition of short interspersed elements. We also found conserved stem-loop structures, which are possibly associated with certain DNA rearrangements responsible for the increase in copy number within a chromosome arm. Such an atypical combination of characteristics (i.e., wide dispersal and tandem repetition) may have been generated by these different transposition mechanisms during the course of evolution.

Animals↗

PubMed1995

Characterization of the large deletion in the GALC gene found in patients with Krabbe disease.

Globoid cell leukodystrophy (GLD) of Krabbe disease results from mutations in the galactocerebrosidase (GALC) gene. Previously, we had identified a large deletion in the GALC gene together with a C to T polymorphism at cDNA position 502 in a significant number of cases of infantile Krabbe disease; however, the deletion breakpoint had not been found. In this paper we show that the deletion is approximately 30 kb starting near the middle of the 12 kb intron 10, and includes all of the coding region through exon 17 plus an additional 9 kb. The deletion junction contains a 4 bp direct repeat and is preceded by sequence identified as belonging to the Alu family of interspersed repetitive elements. Using genomic DNA and a PCR-based test to detect normal and deleted sequences at that location, a large number of patients with all clinical types of GLD were analyzed. Of 21 infantile patients found to be heterozygous for the 502T polymorphism reported previously, 15 had the deletion, one could not tested and five, including a Hmong child, did not have the deletion. Sixteen other infantile patients previously tested were found to be either homozygous (10) or heterozygous (6) for the deletion. In addition, five patients with juvenile and adult GLD were found to be heterozygous for the deletion. In every case tested, the deletion was always found on the same allele as the 502T polymorphism. However, other disease-causing mutations have been found on the 502T allele. With careful genotype analysis these families can receive improved genetic information including patient and carrier identification and preimplantation diagnosis.

Animals↗

PubMed2001

Are different kinds of acoustic features processed differently for speech and non-speech sounds?

This study examined how changes in different types of acoustic features are processed in the brain for both speech and non-speech sounds. Event-related potentials (ERPs) were recorded in native Finnish speakers presented with sequences of repetitive vowels (/e/) or complex harmonical tones interspersed with infrequent changes in duration, frequency and either a vowel change (/o/ for vowel sequences) or a double deviant (frequency+duration change for tone sequences). The stimuli were presented monaurally in separate blocks to either the left or right ear. The results showed that speech stimuli were more efficiently processed than harmonical tones as reflected by an enhanced mismatch negativity (MMN) and P3a ERP components. In addition, the duration change in vowels elicited a larger MMN component than the equivalent change in tones. This result might reflect enhanced processing of duration features in the Finnish language in which phoneme duration plays a critical role.

Acoustic Stimulation↗

PubMed2000

Prediction and phylogenetic analysis of mammalian short interspersed elements (SINEs).

The presence of repetitive elements can create serious problems for sequence analysis, especially in the case of homology searches in nucleotide sequence databases. Repetitive elements should be treated carefully by using special programs and databases. In this paper, various aspects of SINE (short interspersed repetitive element) identification, analysis and evolution are discussed.

Animals↗

PubMed1995

The Drosophila salivary gland chromocenter contains highly polytenized subdomains of mitotic heterochromatin.

Peri-centromeric regions of Drosophila melanogaster chromosomes appear heterochromatic in mitotic cells and become greatly underrepresented in giant polytene chromosomes, where they aggregate into a central mass called the chromocenter. We used P elements inserted at sites dispersed throughout much of the mitotic heterochromatin to analyze the fate of 31 individual sites during polytenization. Analysis of DNA sequences flanking many of these elements revealed that middle repetitive or unique sequence DNAs frequently are interspersed with satellite DNAs in mitotic heterochromatin. All nine Y chromosome sites tested were underrepresented > 20-fold on Southern blots of polytene DNA and were rarely or never detected by in situ hybridization to salivary gland chromosomes. In contrast, nine tested insertions in autosomal centromeric heterochromatin were represented fully in salivary gland DNA, despite the fact that at least six were located proximal to known blocks of satellite DNA. The inserted sequences formed diverse, site-specific morphologies in the chromocenter of salivary gland chromosomes, suggesting that domains dispersed at multiple sites in the centromeric heterochromatin of mitotic chromosomes contribute to polytene beta-heterochromatin. We suggest that regions containing heterochromatic genes are organized into dispersed chromatin configurations that are important for their function in vivo.

Animals↗

PubMed1999

RNAs from all categories generate retrosequences that may be exapted as novel genes or regulatory elements.

While the significance of middle repetitive elements had been neglected for a long time, there are again tendencies to ascribe most members of a given middle repetitive sequence family a functional role--as if the discussion of SINE (short interspersed repetitive elements) function only can occupy extreme positions. In this article, I argue that differences between the various classes of retrosequences concern mainly their copy numbers. Consequently, the function of SINEs should be viewed as pragmatic such as, for example, mRNA-derived retrosequences, without underestimating the impact of retroposition for generation of novel protein coding genes or parts thereof (exon shuffling by retroposition) and in particular of SINEs (and retroelements) in modulating genes and their expression. Rapid genomic change by accumulating retrosequences may even facilitate speciation [McDonald, J.F., 1995. Transposable elements: possible catalysts of organismic evolution. Trends Ecol. Evol. 10, 123-126.] In addition to providing mobile regulatory elements, small RNA-derived retrosequences including SINEs can, in analogy to mRNA-derived retrosequences, also give rise to novel small RNA genes. Perhaps not representative for all SINE/master gene relationships, we gained significant knowledge by studying the small neuronal non-messenger RNAs, namely BC1 RNA in rodents and BC200 RNA in primates. BC1 is the first identified master gene generating a subclass of ID repetitive elements, and BC200 is the only known Alu element (monomeric) that was exapted as a novel small RNA encoding gene.

Animals↗

PubMed1988

Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man.

L1 sequences are a human-specific family of long, interspersed, repetitive elements, present as approximately 10(5) copies dispersed throughout the genome. The full-length L1 sequence is 6.1 kilobases, but the majority of L1 elements are truncated at the 5' end, resulting in a fivefold higher copy number of 3' sequences. The nucleotide sequence of L1 elements includes an A-rich 3' end and two long open reading frames (orf-1 and orf-2), the second of which encodes a potential polypeptide having sequence homology with the reverse transcriptases. This structure suggests that L1 elements represent a class of non-viral retrotransposons. A number of L1 complementary DNAs, including a nearly full-length element, have been isolated from an undifferentiated teratocarcinoma cell line. We now report insertions of L1 elements into exon 14 of the factor VIII gene in two of 240 unrelated patients with haemophilia A. Both of these insertions (3.8 and 2.3 kilobases respectively) contain 3' portions of the L1 sequence, including the poly (A) tract, and create target site duplications of at least 12 and 13 nucleotides of the factor VIII gene. In addition, their 3'-trailer sequences following orf-2 are nearly identical to the consensus sequence of L1 cDNAs (ref. 6). These results indicate that certain L1 sequences in man can be dispersed, presumably by an RNA intermediate, and cause disease by insertional mutation.

Base Sequence↗

PubMed2000

Mismatch negativity and behavioural discrimination in humans as a function of the magnitude of change in sound duration.

This study investigated how duration changes are processed in the human brain as indexed by the mismatch negativity (MMN), a component of the auditory event-related potential (ERP) reflecting sensory memory. Subjects were presented with sequences of repetitive 100-ms white noise bursts interspersed by occasional duration deviants which were 1, 10, or 50 ms (decrements) or 110, 150, or 200 ms (increments) in duration. In a separate task, subjects were asked to detect deviants within the sequence via a button-press. MMN was elicited by both stimulus decrements and increments and increased in amplitude as a function of the amount of deviation from the standard duration except for the shortest, 1-ms deviant. Behavioural detection paralleled the MMN responses, suggesting a link between the processes underlying MMN and behavioural measures.

Acoustic Stimulation↗

PubMed2003

Mismatch negativity indexes auditory temporal resolution: evidence from event-related potential (ERP) and event-related field (ERF) recordings.

This study examined auditory temporal resolution as indexed by gap detection using the mismatch negativity (MMN) component of the auditory event-related potential (ERP) and its magnetic counterpart (MMNm). ERPs were recorded in 10 subjects who were presented with auditory stimuli. These stimuli were presented in sequences of repetitive continuous 'standard' sinusoidal tones interspersed with infrequently occurring 'deviant' stimuli that differed from standards only in that they contained a silent gap midway in the stimulus. The gap size varied in separate stimulus blocks and was either 3, 5 or 7 ms. The stimuli were presented monaurally either to the left or the right ear. In a separate session, event-related magnetic fields (ERFs) were recorded from eight subjects using a similar paradigm but with gap sizes of 3, 7 or 11 ms and with binaural stimulation. Both ERP and ERF recordings showed that the smallest gap size (3 ms) did not elicit as large or reliable MMN or MMNm as did the larger ones. There were no differences in the laterality of the MMN as might be predicted on the basis of previous behavioural studies, but this result is likely a reflection of differences in task requirements. Nonetheless, the findings suggest that MMN and MMNm successfully index auditory temporal resolution thresholds, as measures that are independent of attention.

Acoustic Stimulation↗

PubMed1990

Structure of a protein superfiber: spider dragline silk.

Spider major ampullate (dragline) silk is an extracellular fibrous protein with unique characteristics of strength and elasticity. The silk fiber has been proposed to consist of pseudocrystalline regions of antiparallel beta-sheet interspersed with elastic amorphous segments. The repetitive sequence of a fibroin protein from major ampullate silk of the spider Nephila clavipes was determined from a partial cDNA clone. The repeating unit is a maximum of 34 amino acids long and is not rigidly conserved. The repeat unit is composed of three different segments: (i) a 6 amino acid segment that is conserved in sequence but has deletions of 3 or 6 amino acids in many of the repeats; (ii) a 13 amino acid segment dominated by a polyalanine sequence of 5-7 residues; (iii) a 15 amino acid, highly conserved segment. The latter is predominantly a Gly-Gly-Xaa repeat with Xaa being alanine, tyrosine, leucine, or glutamine. The codon usage for this DNA is highly selective, avoiding the use of cytosine or guanine in the third position. A model for the physical properties of fiber formation, strength, and elasticity, based on this repetitive protein sequence, is presented.

Amino Acid Sequence↗

PubMed2005

Genomewide comparative analysis of the highly abundant transposable element DINE-1 suggests a recent transpositional burst in Drosophila yakuba.

DINE-1 (Drosophila interspersed element) is the most abundant repetitive sequence in the Drosophila genome derived from transposable elements. It comprises >1% of the Drosophila melanogaster genome (DMG) and is believed to be a relic from an ancient transpositional burst that occurred approximately 5-10 MYA. We performed a genomewide comparison of the abundance, sequence variation, and chromosomal distribution of DINE-1 in D. melanogaster and D. yakuba. Unlike the highly diverged copies in the DMG (pairwise distance approximately 15%), DINE-1's in the Drosophila yakuba genome (DYG) have diverged by only 3.4%. Moreover, the chromosomal distribution of DINE-1 in the two species is very different, with a significant number of euchromatic insertions found only in D. yakuba. We propose that these different patterns are caused by a second transpositional burst of DINE-1's in the D. yakuba genome approximately 1.5 MYA. On the basis of the sequence of these recently transposed copies, we conclude that DINE-1 is likely to be a family of nonautomomous DNA transposons. Analysis of the chromosomal distribution of two age groups of DINE-1's in D. yakuba indicates that (1) there is a negative correlation between recombination rates and the density of DINE-1's and (2) younger copies are more evenly distributed in the chromosome arms, while older copies are mostly located near the centromere regions. Our results fit the predictions of a selection-transposition balance model. Our data on whole-genome comparison of a highly abundant TE among Drosophila sibling species demonstrate the unexpectedly dynamic nature of TE activity in different host genomes.

Animals↗

PubMed1994

Enhancement of reporter gene de novo methylation by DNA fragments from the alpha-fetoprotein control region.

The 5'-upstream region of the rat alpha-fetoprotein (AFP) gene strongly increased de novo methylation of an adjacent chloramphenicol acetyltransferase (CAT) gene upon transfection into F9 mouse embryonal carcinoma cells. The same effect was exerted by a distal 775-base pair (bp) fragment and by 300- and 1-kb fragments preceding the transcriptional start site, but not by other parts of the control region. Further division of the larger, strongly active fragments resulted in a gradual decrease of methylation and clonal variation in the methylation patterns. The effect of the 775-bp fragment did not depend on its orientation. It was ablated by insertion of the mouse metallothionein I promoter between the AFP gene fragment and the CAT gene, but not by its insertion upstream of the AFP gene fragment. Two fragments from the AFP control region increasing methylation contained B1 and B2 small interspersed repetitive elements, respectively. B1 and B2 sequences of different origin also acted strongly to increase methylation. These findings support the idea that mammalian genes contain specific sequences involved in regulating their methylation. The effects of these sequences appear to be exerted in cis, to be dependent on proximity, but not on orientation, and to require an optimal size of 500-700 bp. Small retrotransposon sequences within such elements may be particularly effective in attracting de novo methylation.

Animals↗

PubMed1986

Chromosome-specific subfamilies within human alphoid repetitive DNA.

Nucleotide sequence data of about 20 X 10(3) base-pairs of the human tandemly repeated alphoid DNA are presented. The DNA sequences were determined from 45 clones containing EcoRI fragments of alphoid DNA isolated from total genomic DNA. Thirty of the clones contained a complete 340 base-pair dimer unit of the repeat. The remaining clones contained alphoid DNA with fragment lengths of 311, 296, 232, 170 and 108 base-pairs. The sequences obtained were compared with an average alphoid DNA sequence determined by Wu & Manuelidis (1980). The divergences ranged from 0.6 to 24.6% nucleotide changes for the first monomer and from 0 to 17.8% for the second monomer of the repeat. On the basis of identical nucleotide changes at corresponding positions, the individual repeat units could be shown to belong to one of several distinct subfamilies. The number of nucleotide changes defining a subfamily generally constitutes the majority of nucleotide changes found in a member of that subfamily. From an evaluation of the proportion of the total amount of alphoid DNA, which is represented by the clones studied, it is estimated that the number of subfamilies of this repeat may be equal to or exceed the number of chromosomes. The expected presence of only one or a few distinct subfamilies on individual chromosomes is supported by the study, also presented, of the nucleotide sequence of 17 cloned fragments of alphoid repetitive DNA from chromosome 7. These chromosome-specific repeats all contain the characteristic pattern of 36 common nucleotide changes that defines one of the subfamilies described. A unique restriction endonuclease (NlaIII) cleavage site present in this subfamily may be useful as a genetic marker of this chromosome. A family member of the interspersed Alu repetitive DNA was also isolated and sequenced. This Alu repeat has been inserted into the human alphoid repetitive DNA, in the same way as the insertion of an Alu repeat into the African green monkey alphoid DNA.

Base Sequence↗