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 469 records · Page 26Linked to original sources
PubMed1993

Alu and L1 sequence distributions in Xq24-q28 and their comparative utility in YAC contig assembly and verification.

The contents of Alu- and L1-containing TaqI restriction fragments were assessed by Southern blot analyses across YAC contigs already assembled by other means and localized within Xq24-q28. Fingerprinting patterns of YACs in contigs were concordant, and using software based on that of M. V. Olson et al. (1986, Proc. Natl. Acad. Sci. USA 83: 7826) to analyze digitized data on fragment sizes, fingerprinting itself could establish matches among about 40% of a test group of 435 YACs. At 100-kb resolution, both repetitive elements were found throughout the region, with no apparent enrichment of Alu or L1 in DNA of G compared to that found in R bands. However, consistent with a random overall distribution, delimited regions of up to 100 kb contained clusters of repetitive elements. The local concentrations may help to account for the reported differential hybridization of Alu and L1 probes to segments of metaphase chromosomes.

Chromosome Mapping↗
PubMed2001

Comprehensive genome sequence analysis of a breast cancer amplicon.

Gene amplification occurs in most solid tumors and is associated with poor prognosis. Amplification of 20q13.2 is common to several tumor types including breast cancer. The 1 Mb of sequence spanning the 20q13.2 breast cancer amplicon is one of the most exhaustively studied segments of the human genome. These studies have included amplicon mapping by comparative genomic hybridization (CGH), fluorescent in-situ hybridization (FISH), array-CGH, quantitative microsatellite analysis (QUMA), and functional genomic studies. Together these studies revealed a complex amplicon structure suggesting the presence of at least two driver genes in some tumors. One of these, ZNF217, is capable of immortalizing human mammary epithelial cells (HMEC) when overexpressed. In addition, we now report the sequencing of this region in human and mouse, and on quantitative expression studies in tumors. Amplicon localization now is straightforward and the availability of human and mouse genomic sequence facilitates their functional analysis. However, comprehensive annotation of megabase-scale regions requires integration of vast amounts of information. We present a system for integrative analysis and demonstrate its utility on 1.2 Mb of sequence spanning the 20q13.2 breast cancer amplicon and 865 kb of syntenic murine sequence. We integrate tumor genome copy number measurements with exhaustive genome landscape mapping, showing that amplicon boundaries are associated with maxima in repetitive element density and a region of evolutionary instability. This integration of comprehensive sequence annotation, quantitative expression analysis, and tumor amplicon boundaries provide evidence for an additional driver gene prefoldin 4 (PFDN4), coregulated genes, conserved noncoding regions, and associate repetitive elements with regions of genomic instability at this locus.

Animals↗
PubMed2002

Single-nucleotide polymorphism in repetitive sequences of the human deleted in azoospermia complex.

A simple and inexpensive single-nucleotide polymorphism (SNP) analysis procedure is described that uses the Fotodyne Analyst System equipped with the Gel-Pro Analysis software to compare the relative fluorescent intensity of ethidium bromide stained and MboI restricted amplicons from male individuals. The different intensity ratios reflect the ratio of repetitive elements with and without an MboI restriction enzyme site. The polymerase chain reaction (PCR) products represent a reiterated sequence within the Y-linked deleted in azoospermia (DAZ) complex involved in male fertility in humans. This procedure was utilized to determine the ratio of MboI(+) and MboI(-) repetitive sequences in 32 male individuals from two human populations, the Buryat from Mongolia and the Mayan from Yucatan. The proportion of wildtype to mutant amplicons was found to vary from 0 to 100% among individuals. This technique is well suited for large-scale analysis of the locus investigated in this manuscript and other similar polymorphisms. This approach may contribute to the study of recent human evolution based on Y-chromosome analysis as well as medical and developmental issues concerning the significance of these repetitive elements in male infertility.

Base Sequence↗
PubMed2025

Enhancer activation from transposable elements in extrachromosomal DNA.

Extrachromosomal DNA (ecDNA) drives oncogene amplification and intratumoral heterogeneity in aggressive cancers. While transposable element (TE) reactivation is common in cancer, its role on ecDNA remains unexplored. Here, we map the 3D architecture of MYC-amplified ecDNA in colorectal cancer cells and identify 68 ecDNA-interacting elements (EIEs)-genomic loci enriched for TEs that are frequently integrated onto ecDNA. We focus on an L1M4a1#LINE/L1 fragment co-amplified with MYC, which functions only in the ecDNA amplified context. Using CRISPR-CATCH, CRISPR interference, and reporter assays, we confirm its presence on ecDNA, enhancer activity, and essentiality for cancer cell fitness. These findings reveal that repetitive elements can be reactivated and co-opted as functional rather than inactive sequences on ecDNA, potentially driving oncogene expression and tumor evolution. Our study uncovers a mechanism by which ecDNA harnesses repetitive elements to shape cancer phenotypes, with implications for diagnosis and therapy.

Journal Article↗
PubMedDate not supplied

Association of short alleles of a VNTR of the serotonin transporter gene with anxiety symptoms in patients presenting after deliberate self harm.

The polymorphism of a variable number tandem repeat (VNTR) region of the serotonin transporter gene consists of three alleles containing, respectively, 9 (STin2.9), 10 (STin2.10) and 12 (STin2.12) copies of a repetitive element. The frequencies of the three alleles in 384 individuals presenting after deliberate self harm were the same as a group of 346 controls. However, ratings of anxiety (and state anger) were higher in those patients with genotypes including the shorter repetitive elements. The findings support the hypothesis that, in this group of patients with low rates of severe psychiatric disorder, allelic variation in the serotonin transporter gene may contribute to the expression of anxiety symptoms.

Aggression↗
PubMed1995

Cloning of a novel polymorphic GC-rich repetitive DNA from Mycobacterium bovis.

A repetitive DNA from a wild-type Mycobacterium bovis isolate was cloned and characterized. The repeated segment was present in M. bovis and M. tuberculosis but was absent from the six other mycobacteria tested. Sequence analysis demonstrated that this repetitive element belonged to the polymorphic GC-rich repeat sequence type, a family of interspersed repeated DNA. This fragment, when used as a probe in restriction fragment length polymorphism analyses, was able to detect polymorphism in M. bovis genotypes that went undetected when the established IS6110 was used as a probe. This repetitive element should be useful in epidemiological studies of bovine tuberculosis.

Base Sequence↗
PubMed1992

Characterization of the primate-specific repetitive DNA element MER1.

Computer analyses of the 3'-flanking DNA sequence of the human elastase I gene revealed a significant degree of similarity with seven human gene sequences in the GenBank and EMBL databases. Genomic Southern analysis indicates that the shared nucleotide sequences are a primate-specific family of short interspersed elements. These elements are members of MER1 sequences (medium reiteration frequency sequences). The consensus sequence of MER1 repeats spans 543 nucleotides and contains several inverted repeats. Since the copy number of MER1 elements seems to be much smaller than that of Alu and L1 repeats, MER1 elements may provide useful landmarks marks for human genome mapping.

Animals↗
PubMed1997

Markedly reduced activity of mutant calcium-sensing receptor with an inserted Alu element from a kindred with familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.

Missense mutations have been identified in the coding region of the extracellular calcium-sensing receptor (CASR) gene and cause human autosomal dominant hypo- and hypercalcemic disorders. The functional effects of several of these mutations have been characterized in either Xenopus laevis oocytes or in human embryonic kidney (HEK293) cells. All of the mutations that have been examined to date, however, cause single putative amino acid substitutions. In this report, we studied a mutant CASR with an Alu-repetitive element inserted at codon 876, which was identified in affected members of families with the hypercalcemic disorders, familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), to understand how this insertion affects CASR function. After cloning of the Alu-repetitive element into the wild-type CASR cDNA, we transiently expressed the mutant receptor in HEK293 cells. Expression of mutant and wild-type receptors was assessed by Western analysis, and the effects of the mutation on extracellular calcium (Ca2+(o)) and gadolinium (Gd3+(o)) elicited increases in the cytosolic calcium concentration (Ca2+(i)) were examined in fura-2-loaded cells using dual wavelength fluorimetry. The insertion resulted in truncated receptor species that had molecular masses some 30 kD less than that of the wild-type CASR and exhibited no Ca2+(i) responses to either Ca2+(o) or Gd3+(o). A similar result was observed with a mutated CASR truncated at residue 876. However, the Alu mutant receptor had no impact on the function of the coexpressed wild-type receptor. Interestingly, the Alu mutant receptor demonstrated decreased cell surface expression relative to the wild-type receptor, whereas the CASR (A877stop) mutant exhibited increased cell surface expression. Thus, like the missense mutations that have been characterized to date in families with FHH, the Alu insertion in this family is a loss-of-function mutation that produces hypercalcemia by reducing the number of normally functional CASRs on the surface of parathyroid and kidney cells. In vitro transcription of exon 7 of the CASR containing the Alu sequence yielded the full-length mutant product and an additional shorter product that was truncated due to stalling of the polymerase at the poly(T) tract. In vitro translation of the mutant transcript yielded three truncated protein products representing termination in all three reading frames at stop codons within the Alu insertion. Thus sequences within the Alu contribute to slippage or frameshift mutagenesis during transcription and/or translation.

Animals↗
PubMed1993

Human chromosome 5 sequence primer amplifies Alu polymorphisms on chromosomes 2 and 17.

Members of the Alu family of repetitive elements occur frequently in the human genome and are often polymorphic. Techniques involving Alu element mediated polymerase chain reactions (Alu PCR) allow the isolation of region-specific human DNA fragments from mixed DNA sources. Such fragments are a source of region-specific Alu elements useful for the detection of Alu-related polymorphisms. A clone from human chromosome 5, corresponding to locus D5F40S1, was isolated using Alu PCR differential hybridization. Alu elements within this clone were investigated for the presence of potentially polymorphic 3' polyA tails. Primers were devised to amplify the 3' polyA tail of an Alu element present within the clone. One primer, D5F40S1-T, was specific to the DNA flanking the 3' end of the Alu element, and the other primer was homologous to sequences within the element. When these primers were used in PCR reactions, products from chromosomes 2 and 17 (loci D2F40S2 and D17F40S3) were amplified in addition to the expected product from chromosome 5. The most likely explanation for this nonspecific amplification is that the D5F40S1-T primer is located within a low-copy repetitive element that is 3' of the Alu element. This phenomenon presents a potential problem for the identification of region-specific Alu polymorphisms.

Animals↗
PubMed1999

Structural bistability of repetitive DNA elements featuring CA/TG dinucleotide steps and mode of evolution of satellite DNA.

Satellite DNA sequences are known to be important components required for the construction of centromeres and are common to all higher eukaryotes. Nevertheless, their nucleotide sequences vary significantly, even in evolutionarily related species. In order to elucidate how the nucleotide sequences define the conformational character of centromeric satellite DNA, an evolutionary path toward repetitive units has been hypothesized. In that context, the DNA conformation of fish satellite DNA was evaluated in two ways: the organization of subrepeats and sequence characteristics were compared, and the differences in stacking energies between A-helix and B-helix and the sequence-dependent bendability of the helices were evaluated. Our findings suggest that the monomeric units making up currently observed repetitive sequences have evolved through stepwise amplification of shorter, ancestral sequences by increasing the length of the units. In addition, we suggest that potentially key sequences required for DNA amplification comprise highly flexible structures. Thus flexibility of the DNA structure may be a primary prerequisite for DNA amplification.

Animals↗
PubMed2003

Comparative sequence analysis of the PRKAG3 region between human and pig: evolution of repetitive sequences and potential new exons.

The PRKAG3 gene encodes the gamma3 chain of AMP-activated protein kinase (AMPK). A non-conservative missense mutation in the PRKAG3 gene causes a dominant phenotype involving abnormally high glycogen content in pig skeletal muscle. We have determined >126 kb (in 13 contigs) of porcine genomic sequence surrounding the PRKAG3 gene and the corresponding mouse region covering the gene. A comparison of these PRKAG3 sequences and the human sequence was conducted and used to predict evolutionarily conserved regions, including regulatory regions. A comparison of the human genomic sequence and a porcine BAC sequence containing the PRKAG3 gene, revealed a conserved organization and the presence of three additional genes, CYP27A1 (cytochrome P450, family 27, subfamily A, polypeptide 1), STK36 (Serine Threonine Kinase 36), and the homolog of the unidentified human mRNA KIAA0173. Interspersed repetitive elements constituted 51.4 and 38.6% of this genomic region in human and pig, respectively. We were able to reliably align 12.6 kb of orthologous repeats shared between pig and human and these showed an average sequence identity of 72.4%. Our analysis revealed that the human KIAA0173 gene harbors alternative 5' untranslated exons originating from repetitive elements. This provides an obvious example how transposable elements may affect gene evolution.

5' Untranslated Regions↗
PubMed1991

Evidence for a relationship between the Bombyx mori middle repetitive Bm1 sequence family and U1 snRNA.

Several genomic library equivalents of Bombyx mori were constructed in the EMBL-4 lambda derivative. The genomic bank was screened with purified Bombyx mori U1 RNA and twenty positive clones for the U1 gene were isolated. Three U1-related sequences were subcloned and sequenced. Two of the sequences are U1 pseudogenes while a third sequence represents a member of the Bm 1 family of repetitive elements of B.mori with significant sequence similarity to U1 small nuclear RNA. The U1-related Bm1 element exhibits 82% sequence similarity with the Bm1 consensus sequence and, under less stringent computer comparison parameters, 60% similarity with a composite B.mori/Drosophila melanogaster U1 gene. The Bm1 family consensus sequence exhibits 53% sequence similarity with the composite U1 gene. The two pseudogenes possess highly conserved sequences with the B.mori U1 gene only for the first 101 nucleotides. These findings are indicative of at least two different categories of U1-related sequences in B.mori, one with a possible evolutionary relationship to the Bm1 family of repetitive elements and the other representing characteristic processed pseudogenes with retroposon mode of dispersion and target selection for the TTTA hotspot. In addition, the U1-related Bm1 element may demonstrate for the first time that a family of retroposons is ultimately derived from a U snRNA.

Animals↗
PubMed1989

Complete nucleotide sequence of the rabbit beta-like globin gene cluster: insights into evolution and regulation.

The general pattern of sequence matches between the beta-like globin gene clusters of rabbits and humans are summarized in Fig. 7. The regions of matching sequences are shaded, and it can be seen that the matches extend from one end of the gene cluster to the other. This provides very strong evidence that the ancestral species had a gene cluster containing the parents to all the contemporary beta-like globin genes in the same arrangement that we observe today. Much of the intergenic DNA has been diverging at a rate consistent with neutral drift, but smaller regions can be detected that are diverging more slowly and which are good candidates for functional sequences. The comparisons between this same gene cluster in mouse and humans show many fewer matches in the intergenic regions (Shehee et al., 1989), indicating either an earlier split between rodents and primates or a faster rate of divergence in rodents. However, this more divergent sequence may prove particularly valuable in a search for functional sequences, especially in a three-way alignment between the sequenced gene clusters. Every repetitive element in homologous segments of the rabbit and human beta-like globin gene clusters interrupts the homology; no repeat is in the same position in both species. Hence all the repeats have been inserted into the gene clusters after the divergence between lagomorphs and primates. This is true even for the L1 repeats, which are very similar between species in their ORF regions. This pattern of interspersion of repeats in long orthologous regions shows that many members of the LINE and SINE families are recent additions to the genome, and that these repeats are in fact transposable elements. It is easy to imagine negative and neutral effects of the expansion and transpositions of these repeat families, but some positive effect has not been ruled out. One of the intriguing inferences from the observations about repeats is that the ancestral gene cluster may not have contained repetitive elements. If it did, then those repeats have been completely replaced by different repeats independently in lagomorphs and primates.

Animals↗
PubMed1998

Comparative sequence analysis of a gene-rich cluster at human chromosome 12p13 and its syntenic region in mouse chromosome 6.

The Human Genome Project has created a formidable challenge: the extraction of biological information from extensive amounts of raw sequence. With the increasing availability of genomic sequence from other species, one approach to extracting coding and regulatory element information is through cross-species sequence comparison. To assess the strengths and weaknesses of this methodology for large-scale sequence analysis, 227 kb of mouse sequence syntenic to a gene-rich cluster on human chromosome 12p13 was obtained. Primarily through percent identity plots (PIPs) of SIM comparative sequence alignments, the sequence of coding regions, putative alternative exons, conserved noncoding regions, and correlation in repetitive element insertions were easily determined. The analysis demonstrated that the number, order, and orientation of all 17 genes are conserved between the two species, whereas two human pseudogenes are absent in mouse. In addition, apart from MIRs, no direct correlation of distribution or position of the majority of repetitive elements between the two species is seen. Finally, in examining the synonymous and nonsynonymous substitution rates in the conserved genes, a large variation in nonsynonymous rates is observed indicating that the genes in this region are diverging at different rates. This study indicates the utility and strength of large-scale cross-species sequence comparisons in the extraction of biological information from raw sequence, especially when combined with other computational tools such as GRAIL and BLAST.

Amino Acid Sequence↗
PubMed1995

Rat karyotyping by fluorescence in situ hybridization (FISH): localization of oncogene c-raf to 4q42, retinoblastoma antioncogene to 15q12, and mitochondrial D-loop-like sequences to the Y chromosome.

Fluorescence in situ hybridization (FISH) has been used to karyotype the rat genome with long interspersed repetitive elements (LINEs). Two-color FISH experiments were used to localize the rat c-raf oncogene to 4q42 and the rat retinoblastoma anti-oncogene to 15q12. In addition, sequences similar to the rat mitochondrial origin of replication (D-loop-like sequences) have been found to be concentrated among repetitive element sequences on the Y chromosome. This report extends hybridization-based karyotype technology to the rat, thus facilitating the application of FISH to rat gene mapping.

Animals↗
PubMed1990

Repetitive sequence elements in an initiation locus of the amplified dihydrofolate reductase domain in CHO cells.

We have previously demonstrated that one of the replication initiation loci in the dihydrofolate reductase (DHFR) domain of Chinese hamster cells contains a repeated sequence that is enriched in the early-replicating fraction of the Chinese hamster genome. Here we present the sequence of the initiation locus, identify the relevant repeated element, and show that, while this element is enriched in early-replicating DNA, its synthesis is not confined to early S.

Animals↗
PubMed1998

Genotype and virulence correlation within Mexican stocks of Trypanosoma cruzi isolated from patients.

Five Trypanosoma cruzi stocks were isolated from infected patients in the central state of Jalisco, Mexico. Parasites were isolated by direct inoculation of infected blood into BALB/c mice. The five stocks of T. cruzi were analyzed for in vitro growth, and for virulence and parasitic load in vivo. Furthermore, a genetic analysis based on restriction fragment length polymorphism associated with a repetitive element from the rRNA gene spacer was performed. No differences in in vitro growth or in parasitic load in vivo were found among the stocks. While three stocks showed low virulence for mice, the other two stocks killed 80 and 100% of the infected mice. In addition, Southern blot of total DNA hybridized with a repetitive element from the rRNA gene spacer showed two clearly distinct patterns that correlated with the observed ability of the stocks to kill infected mice. Our results show a correlation among the ability to kill BALB/c mice, the genetic pattern and clinical symptoms produced by the different stocks in the infected patients.

Adult↗