SEARCH · PubMed Health

Results for “genomic tandem array”

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 253 records · Page 14Linked to original sources

PubMed1996

Two-dimensional RFLP analyses reveal megabase-sized clusters of rRNA gene variants in Arabidopsis thaliana, suggesting local spreading of variants as the mode for gene homogenization during concerted evolution.

Eukaryotic genes encoding the precursor of 18S, 5.8S and 25S ribosomal RNA (rRNA genes or rDNA) are virtually identical within a species, yet they evolve rapidly between species, a phenomenon known as concerted evolution. The mechanisms by which sequence homogenization and fixation of new rRNA gene variants occurs within a genome are not clear. In diploid Arabidopsis thaliana, approximately 1500 rRNA genes are tandemly arrayed at two nucleolus organizer regions, one on chromosome 2 (NOR2), the other on chromosome 4 (NOR4). This paper shows that NOR2 and NOR4 are similar in size, each spanning approximately 3.5-4.0 Mbp. Using two-dimensional mapping techniques involving a combination of pulsed-field and conventional gel electrophoresis, the distributions of four distinct rRNA gene variants at NOR2 and NOR4 have been determined. rRNA genes at NOR4 are homogeneous with respect to a HindIII site occurring once per gene. In contrast, fewer than 10% of the rRNA genes at NOR2 are HindIII-bearing variants. A single intergenic spacer length is found among rRNA genes at NOR2 but three classes of spacer length variants are present at NOR4. The NOR4 variants are not intermingled with one another; instead, they are highly clustered over distances as large as 1.5 Mbp. These data suggest that in the concerted evolution of rRNA genes, homogenization is a consequence of local spreading of new rRNA gene variants.

Arabidopsis↗

PubMed1989

Identification of temperature-sensitive mutants of vaccinia virus that are defective in conversion of concatemeric replicative intermediates to the mature linear DNA genome.

Pulsed-field gel electrophoresis was used to screen temperature-sensitive mutants of vaccinia virus for the ability to convert replicated viral DNA into mature linear 185-kilobase hairpin-terminated genomes. Of 30 mutually noncomplementing mutants tested, 5 displayed a temperature-sensitive defect in the resolution of the telomere fusion configuration within concatemeric replicative intermediates, resulting in a failure to convert such intermediates to the linear monomeric genome. Adjacent genomic units in the concatemeric arrays generated in these mutants were arranged in both tandem and inverted orientations. The observation that four of the five mutants had a severe general defect in the synthesis of the late class of viral proteins suggests that at least one late protein is directly required to resolve the telomere fusion intermediate to hairpin termini. The identification of such telomere resolution proteins should be facilitated by genetic and molecular characterization of resolution-defective mutants, such as C63, in which late protein synthesis is not severely affected.

Animals↗

PubMed2006

Detection of recurrent copy number loss at Yp11.2 involving TSPY gene cluster in prostate cancer using array-based comparative genomic hybridization.

Prostate cancer is the second leading cause of cancer deaths among American men. The loss of Y chromosome has been frequently observed in primary prostate cancer as well as other types of cancer. Earlier, we showed that introduction of the human Y chromosome suppresses the in vivo tumorigenicity of the prostate cancer cell line PC-3. To further characterize the Y chromosome, we have developed a high-density bacterial artificial chromosome (BAC) microarray containing 178 BAC clones from the human Y chromosome. BAC microarray was used for array comparative genomic hybridization on prostate cancer samples and cell lines. The most prominent observation on prostate cancer specimens was a deletion at Yp11.2 containing the TSPY tandem gene array. Out of 36 primary prostate tumors analyzed, 16 (44.4%) samples exhibited loss of TSPY gene copies. Notably, we observed association between the number of TSPY copies in the blood and the incidence of prostate cancer. Moreover, PC-3 hybrids with an intact Yp11.2 did not grow tumors in nude mice, whereas PC-3 hybrids with a deletion at Yp11.2 grew tumors in nude mice.

Aged↗

PubMed1991

The centromere region of Arabidopsis thaliana chromosome 1 contains telomere-similar sequences.

We describe the structure of an Arabidopsis thaliana genomic clone containing two classes of repetitive DNA elements derived from the centromere region of chromosome 1. One class is comprised of tandem arrays of a highly reiterated repeat containing degenerate telomere sequence motifs. Adjacent to these telomere-similar repeats we found a dispersed repetitive element reiterated approximately five times in the A. thaliana genome. The nucleotide sequence of the dispersed repeat is unusual, being extremely AT-rich and composed of numerous, overlapping repeat motifs.

Base Sequence↗

PubMed1984

A new family of tandem repetitive early histone genes in the sea urchin Lytechinus pictus: evidence for concerted evolution within tandem arrays.

We have isolated and characterized a third nonallelic tandemly arrayed histone cluster (LpE) from the sea urchin Lytechinus pictus. Although this tandem array is not intermingled with the other two early histone gene families also found in the L. pictus genome, the order and polarity of the five histone coding sequences in this family are the same as every other well characterized sea urchin early histone gene family. Heteroduplex analysis and restriction endonuclease mapping experiments indicate that the LpE family is more closely related to the B-C than the A-D family of early histone genes. Examination of several individual sperm DNA samples has revealed considerable polymorphism in each of the three tandem repeat families. Within an individual, however, each family is remarkably homogeneous. Thus, our results indicate that rapid fixation of variants acts to homogenize the members of a single tandem array at a considerably faster rate within a family than between families. However, at least some exchange of sequences between families is evident based on the conservation of many restriction endonuclease recognition sites and from analysis of a a cosmid clone in which the A-D and E tandem repeats are found adjacent to one another. These differences in the rate of fixation of variants within and between these families are likely to be responsible for the maintenance of diversity between the different families.

Animals↗

PubMed2000

Genomic sequence and transcriptional profile of the boundary between pericentromeric satellites and genes on human chromosome arm 10q.

The organization of centromeric heterochromatin has been established in a number of eucaryotes but remains poorly defined in human. Here we present 1025 kb of contiguous human genomic sequence which links pericentromeric satellites to the RET proto-oncogene in 10q11.2 and is presumed to span the transition from centric heterochromatin to euchromatin on this chromosome arm. Two distinct domains can be defined within the sequence. The proximal approximately 240 kb consists of arrays of satellites and other tandem repeats separated by tracts of complex sequence which have evolved by pericentromeric-directed duplication. Analysis of 32 human paralogues of these sequences indicates that most terminate at or within repeat arrays, implicating these repeats in the interchromosomal duplication process. Corroborative PCR-based analyses establish a genome-wide correlation between the distribution of these paralogues and the distribution of satellite families present in 10q11. In contrast, the distal approximately 780 kb contains few tandem repeats and is largely chromosome specific. However, a minimum of three independent intrachromosomal duplication events have resulted in >370 kb of this sequence sharing >90% identity with sequences on 10p. Using computer-based analyses and RT-PCR we confirm the presence of three genes within the sequence, ZNF11/33B, KIAA0187 and RET, in addition to five transcripts of unknown structure. All of these transcribed sequences map distal to the satellite arrays. The boundary between satellite-rich interchromosomally duplicated DNA and chromosome-specific DNA therefore appears to define a transition from pericentromeric heterochromatin to euchromatin on the long arm of this chromosome.

Centromere↗

PubMed1991

Two dispersed highly repeated DNA families of Triturus vulgaris meridionalis (Amphibia, Urodela) are widely conserved among Salamandridae.

Two BamHI families of repeated sequences were characterized from the genome of the Italian smooth newt, Triturus vulgaris meridionalis (Amphibia, Urodela). The first family, which is divided into subfamilies, consists of tandemly arranged arrays whose basic repeat is around 398 bp long; these arrays are dispersed throughout the entire chromosome sets of the various species of Triturus tested. Moreover the family is widely conserved among Salamandridae, being detected by genomic DNA blotting of Notophthalmus viridescens, Taricha granulosa, Salamandrina terdigitata and Euproctus platycephalus. The second BamHI family is represented by a cloned sequence of 419 bp, which is dispersed in the chromosome set of several species of Triturus. The sequence is also conserved in S. terdigitata and in E. platycephalus but is not detectable in N. viridescens or T. granulosa. The cloned sequence is most probably only part of a longer unit interspersed within the Triturus genome.

Animals↗

PubMed1996

The evolutionary distribution and structural organization of the homeobox-containing repeat D4Z4 indicates a functional role for the ancestral copy in the FSHD region.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disease that has been linked to deletions within a tandem array of 3.2 kb repeats adjacent to the telomere of 4q. These repeats are also present in other locations in the human genome, including the short arms of all the acrocentric chromosomes. Here, we examine two models for the role of this repeat in FSHD. First, because of the extensive similarity between the 3.2 kb repeats on 4q and those adjacent to rDNA on the acrocentric chromosomes, we investigated whether the FSHD region on 4q is involved in sub-nuclear localization, specifically to the nucleolus. The results likely exclude any involvement of nucleolar localization in the development of FSHD. Second, we investigated a model that suggests that a functional gene may be buried within the tandem array of 3.2 kb repeats. Toward this end, we evaluated the evolutionary conservation of the repeat and a double homeodomain sequence within the repeat in a variety of primate species. The genomic organization of the 3.2 kb repeat in humans, great apes and lower primates identified the FSHD-associated repeat on chromosome 4q as the likely ancestral copy. The sequence of the rhesus monkey double homeodomain reveals significant sequence identity with the human 4q sequence. These results strongly suggest a functional role for a component of the FSHD-associated repeat.

Amino Acid Sequence↗

PubMed2005

Heteroduplex analysis of minisatellite variability.

Minisatellites are tandem repeat arrays of middle size (5-100 bp) repeat units widely distributed in eukaryotic genomes. They have been related to several important features of human genome biology, including gene regulation, chromosomal fragile sites, and imprinting. In this report, we have critically assessed and employed heteroduplex analysis (HA) for the identification of different human minisatellite MsH43 alleles. This minisatellite is organized as a repeat array of 5-6 bp units spanning 0.5 kbp. Our results demonstrate that this procedure is an easy, rapid, and reliable method to document allelic diversity for this locus. This work suggests that HA will also be a useful tool for studying the polymorphism of other minisatellites with small repeat units.

Chromosomes, Human, Pair 2↗

PubMed2000

Tetrad analysis shows that gene conversion is the major mechanism involved in mutation at the human minisatellite MS1 integrated in Saccharomyces cerevisiae.

Minisatellites are arrays of tandemly repeated DNA sequences which occur at thousands of locations in the human genome. They are frequently hypervariable with respect to allele length as a result of high rates of complex and incompletely understood recombination-based germline mutation events that alter the repeat copy number. MS1 is one of the most variable minisatellites so far isolated from the human genome. We have integrated MS1, flanked by synthetic markers, in the vicinity of a hot spot for meiotic double-strand breaks upstream of the LEU2 locus in chromosome III of Saccharomyces cerevisiae. Here we present the first tetrad analysis of mutations at a human minisatellite locus. The data showed that mutant alleles occur as single mutants in one of the spores in a tetrad, also when the mutant structure was the result of a combination of intra- and inter-allelic rearrangements. The conversional transfer of repeat units from one allele to the other was associated with flanking marker conversion which always involved the same flank of the minisatellite. The results demonstrate that conversion is the predominant mechanism by which minisatellite alleles mutate to new lengths, and also support the assumption that cis-acting elements are involved in the regulation of the mutational process in humans.

Base Sequence↗

PubMed1998

Chimeric amplicons containing the c-myc gene in HL60 cells.

The major amplicon present in HL60 cells is chimeric in nature being composed of 70 kb of DNA sequence derived from the MYC locus linked to 80 kb of novel DNA sequence derived from a non contiguous region located telomeric to the c-myc gene at 8q24 (Feo et al., 1996). Here we show by fluorescence in situ hybridization (FISH) that these coamplified sequences, MCR (Myc Coamplified Region), are derived from a locus located 3-4 Mb telomeric to the c-myc gene in the q24.2-24.3 region of chromosome 8. Genomic cloning and Southern blot analysis indicate the arrangement of chimeric amplicons are in tandem arrays. Analysis of the DNA sequences at the juncture of the MYC locus and the MCR suggest that these non syntenic regions were joined by nonhomologous recombination events. Visualization of the organization of the amplified DNA by fiber-FISH analysis illustrates we have cloned the complete amplicon. This is the first complete mammalian amplicon to be cloned and have its structure visualized. In addition to the major class of tandemly repeated amplicons, a second class of amplicons was detected by fiber-FISH in which the extent of the MCR component is about twice the size of the MCR component in the major amplicon. These longer amplicons most likely contain inverted repeats of MCR and MYC region sequences. Whether the amplicons contain mixtures of these two types of structures or separate amplicons only contain one type of structure has not yet been resolved. Properties of the MCR sequences responsible for retention in the chimeric HL60 amplicons upon long term passage are discussed.

Base Sequence↗

PubMed2002

Zinc finger gene clusters and tandem gene duplication.

Zinc finger genes in mammalian genomes are frequently found to occur in clusters with cluster members appearing in a tandem array on the chromosome. It has been suggested that in situ gene duplication events are primarily responsible for the evolution of such clusters. The problem of inferring the series of duplication events responsible for producing clustered families is different from the standard phylogeny problem. In this paper, we study this inference problem using a graph called duplication model that captures the series of duplication events while taking into account the observed order of the genes on the chromosome. We provide algorithms to reconstruct a duplication model for a given data set. We use our method to hypothesize the series of duplication events that may have produced the ZNF45 family that appears on human chromosome 19.

Algorithms↗

PubMed2025

Heterochromatin-based silencing of a foreign tandem repeat in Drosophila melanogaster shows unusual biochemistry and temperature sensitivity.

Eukaryotic genomes are packaged into chromatin, a regulatory nucleoprotein assembly. Establishment, maintenance, and interconversion of chromatin states is required for correct patterns of gene expression, genome integrity, and survival. Transcriptionally repressive heterochromatin minimizes mobilization of transposable elements and limits expansion of other repetitive DNA, but mechanisms for recognition of the latter sequences are not well established. We previously demonstrated in Drosophila melanogaster that transcripts derived from 1360 and Invader4 transposon insertions can trigger local conversion of transcriptionally permissive euchromatin to heterochromatin through the piRNA system, but only in a subset of genomic locations near existing blocks of heterochromatin. Here we show that a ~9 kb tandem array of the 36-nucleotide lac operator (lacO) sequence of Escherichia coli can form ectopic heterochromatin at a similar subset of sites, resulting in variegating expression of an adjacent reporter gene. Heterochromatin Protein 1a (HP1a) and histone deacetylation are required for lacO repeat-induced silencing, but, contrasting with previously described Position Effect Variegation (PEV), we do not observe increased histone H3 lysine 9 methylation. Silencing is effective at 25°C and suppressed at 18°C (in contrast to canonical PEV, which is enhanced at 18°C), indicating involvement of a temperature-sensitive component. Temperature switching experiments show that lacO repeat-induced heterochromatin formation is reversible throughout larval development following an HP1a-dependent initiation step in the early embryo. We conclude that the Drosophila nucleus can recognize a completely foreign tandem repeat as a target for heterochromatin formation, and that the heterochromatin structure established is distinct from that of endogenous tandem arrays.

HP1a↗

PubMed2005

Human ribosomal RNA gene arrays display a broad range of palindromic structures.

The standard model of eukaryotic ribosomal RNA (rRNA) genes involves tandem arrays with hundreds of units in clusters, the nucleolus organizer regions (NORs). A first genomic overview for human cells is reported here for these regions, which have never been sequenced in their totality, by using molecular combing. The rRNA-coding regions are examined by fluorescence on single molecules of DNA with two specific probes that cover their entire length. The standard organization assumed for rDNA units is a transcribed region followed by a nontranscribed spacer. While we confirmed this arrangement in many cases, unorthodox patterns were also observed in normal individuals, with one-third of the rDNA units rearranged to form apparently palindromic structures (noncanonical units) independent of the age of the donors. In cells from individuals with a deficiency in the WRN RecQ helicase (Werner syndrome), the proportion of palindromes increased to one-half. These findings, supported by Southern blot analyses, show that rRNA genes are a mosaic of canonical and (presumably nonfunctional) palindromic units that may be altered by factors associated with genomic instability and pathology.

Blotting, Southern↗

PubMed1984

A murine T cell receptor gene complex: isolation, structure and rearrangement.

We describe here our efforts to develop a systematic strategy for the enumeration and isolation of genes encoding T cell-specific, membrane-associated polypeptides. Of particular importance among the cDNA clones that we have isolated is one which encodes the beta chain of the murine T cell receptor for antigen. The gene product is strikingly similar to immunoglobulin in its variable (V), constant (C), joining (J), and diversity (D) - like elements and the ability of the latter three types of element to assort independently during differentiation. The genomic organization of the constant region locus which encodes this molecule consists of two tandemly arrayed units of the form JC/JC, where the J clusters consist of fourteen distinct elements, many of which may be functional. The two constant regions differ by only four amino acids and both are apparently expressed in T cells of the same phenotype, so they probably do not represent isotypes in the classical sense. The sequences flanking the V, D and J elements are also similar to the conserved heptamer and nonomer sequences of immunoglobulins thought to be important in the recombination of the specific gene segments. These similarities indicate both the common evolutionary origins of these loci and the strong selective pressure that must be operative. The T cell receptor locus differs somewhat from immunoglobulins in the large number of possible J region elements and to some extent in the hypervariable-framework regions of the V region. We and others have mapped this gene to chromosome 6 of the mouse, in the same portion of the chromosome but not closely linked the kappa locus. The significance of the predicted protein structure of the beta chain and its support of the one-receptor model of MHC-antigen recognition are discussed.

Amino Acid Sequence↗

PubMed2001

Non-coordinate expression of closely linked mouse casein genes.

Expression levels of five mouse casein genes were analysed in the mammary gland of virgin, pregnant and lactating mice. We have already shown that the five murine casein genes are arranged in the order, alpha-beta-gamma-epsilon-kappa in a tandem array, very close to each other in a 250 kb DNA fragment of mouse genome. Northern blot analysis showed that, of the calcium-sensitive casein genes, the epsilon casein gene is expressed only during lactation unlike the alpha, beta and gamma casein genes which are expressed during pregnancy and lactation. Even though the alpha, beta and gamma genes exhibited a co-ordinated expression pattern from mid to the later stages of pregnancy, the mRNA levels varied considerably (60, 90 and 100% respectively) by the onset of lactation. The mRNA level of the calcium-insensitive kappa casein gene increased from mid-pregnancy but at a lower rate and reached approximately 60% by the first day of lactation. Considering the locations and closeness of the casein genes, a non-coordinate expression profile is exhibited by the mouse casein genes, particularly the epsilon casein gene.

Animals↗

PubMedDate not supplied

[BspMII-family of tandemly organized DNA sequences of the Baikalian cottoid fish (Cottodei)].

A new family of highly repetitive tandemly arrayed DNA sequences was revealed by electrophoretic analysis of BspMII (T'CCGGA) digest of genomic DNA from Baikalian cottoid fishes. Three such repeats from two species B. nikolskii and P. kneri were cloned and sequenced. The sizes of repeat elements are 238, 154, and 123 bp. All three repeats have highly homologous flanking regions 53 and 63 bp in length. It was shown that chains of DNA repeats had an ability to form stable secondary structures in vitro. It is supposed that shorter repeats (154 and 123 bp) originated from the 238 bp repeat by deletion its central fragments. An element having a the promoter for RNA polymerase III was found within the 238 bp repeat. The origin of this element from one of the tRNA genes is suggested. The possibility of using BspMII repeats as an evolutionary marker for studying the genesis of Cottoidei is discussed.

Animals↗

PubMed2000

CTXphi contains a hybrid genome derived from tandemly integrated elements.

CTXphi is a filamentous, temperate bacteriophage whose genome includes ctxAB, the genes that encode cholera toxin. In toxigenic isolates of Vibrio cholerae, tandem arrays of prophage DNA, usually interspersed with the related genetic element RS1, are integrated site-specifically within the chromosome. We have discovered that these arrays routinely yield hybrid virions, composed of DNA from two adjacent prophages or from a prophage and a downstream RS1. Coding sequences are always derived from the 5' prophage whereas most of an intergenic sequence, intergenic region 1, is always derived from the 3' element. The presence of tandem elements is required for production of virions: V. cholerae strains that contain a solitary prophage rarely yield CTX virions, and the few virions detected result from imprecise excision of prophage DNA. Thus, generation of the replicative form of CTXphi, pCTX, a step that precedes production of virions, does not depend on reversal of the process for site-specific integration of CTXphi DNA into the V. cholerae chromosome. Production of pCTX also does not depend on RecA-mediated homologous recombination between adjacent prophages. We hypothesize that the CTXphi-specific proteins required for replication of pCTX can also function on a chromosomal substrate, and that, unlike the processes used by other integrating phages, production of pCTX and CTXphi does not require excision of the prophage from the chromosome. Use of this replication strategy maximizes vertical transmission of prophage DNA while still enabling dissemination of CTXphi to new hosts.

Bacteriophages↗