SEARCH · PubMed Health

Results for “insertion, inversion”

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 109 records · Page 6Linked to original sources

PubMed1995

I-CeuI reveals conservation of the genome of independent strains of Salmonella typhimurium.

The enzyme I-CeuI, encoded by a class I mobile intron inserted in the gene for 23S rRNA in Chlamydomonas eugamatos, cleaves a specific 19-bp sequence in this gene. This sequence is present only in the seven genes for rRNA in Salmonella typhimurium and Escherichia coli. Partial digestion with I-CeuI of DNA from 17 wild-type strains of S. typhimurium indicates that the chromosome of these strains is strongly conserved, for the digestion products closely resemble those of strain LT2. The lengths and order of chromosomal segments are conserved in 15 of the strains; 2 show some rearrangements. XbaI digestion indicated heterogeneity without revealing the genomic structure. Because of conservation of I-CeuI sites in genes for rRNA and conservation of the number and locations of these genes, I-CeuI provides an excellent tool for the rapid examination of the chromosomes of related species of bacteria; differences in the fingerprints indicate the occurrence of chromosomal rearrangements such as insertions or inversions.

Animals↗

PubMed1996

Phenotypic switching of variable surface lipoproteins in Mycoplasma bovis involves high-frequency chromosomal rearrangements.

Mycoplasma bovis, an important pathogen of cattle, was recently shown to possess a family of phase- and size-variable membrane surface lipoprotein antigens (Vsps). These proteins spontaneously undergo noncoordinate phase variation between ON and OFF expression states, generating surface antigenic variation. In the present study, we show that the spontaneously high rate of Vsp phenotypic switching involves DNA rearrangements that occur at high frequency in the M. bovis chromosome. A 1.5-kb HindIII genomic fragment carrying the vspA gene from M. bovis PG45 was cloned and sequenced. The deduced VspA amino acid sequence revealed that 80% of the VspA molecule is composed of reiterated intragenic coding sequences, creating a periodic polypeptide structure. Four distinct internal regions of repetitive sequences in the form of in-tandem blocks extending from the N-terminal to the C-terminal portion of the Vsp product were identified. Southern blot analysis of phenotypically switched isogenic lineages representing ON or OFF phase states of Vsp products suggested that changes in the Vsp expression profile were associated with detectable changes at the DNA level. By using a synthetic oligonucleotide representing a sequence complementary to the repetitive vspA gene region as a probe, we could identify the vspA-bearing restriction fragment undergoing high-frequency reversible rearrangements during oscillating phase transition of vspA. The 1.5-kb HindIII fragment carrying the vspA gene (on state) rearranged and produced a 2.3-kb HindIII fragment (OFF state) and vice versa. Two newly discovered vsp genes (vspE and vspF) were localized on two HindIII fragments flanking the vsp gene upstream and downstream. Southern blot hybridization with vspE- and vspF-specific oligonucleotides as probes against genomic DNA of VspA phase variants showed that the organization and size of the fragments adjacent to the vspA gene remained unchanged during VspA ON-OFF switching. The mechanisms regulating the vsp genes are yet unknown; our findings suggest that a recombinative mechanism possibly involving DNA inversions, DNA insertion, or mobile genetic elements may play a role in generating the observed high-frequency DNA rearrangements.

Amino Acid Sequence↗

PubMed2005

The complex nature of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes.

OBJECTIVE: To describe the systematic analysis of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes, characterise the structural chromosome rearrangements, map the translocation breakpoints, and report detectable genomic imbalances. METHODS: DNA microarrays were used with a resolution of 1 Mb for the detailed genome-wide analysis of the patients. Array CGH was used to screen for genomic imbalance and array painting to map chromosome breakpoints rapidly. These two methods facilitate rapid analysis of translocation breakpoints and screening for cryptic chromosome imbalance. Breakpoints of rearrangements were further refined (to the level of spanning clones) using fluorescence in situ hybridisation where appropriate. RESULTS: Unexpected additional complexity or genome imbalance was found in six of 10 patients studied. The patients could be grouped according to the general nature of the karyotype rearrangement as follows: (A) three cases with complex multiple rearrangements including deletions, inversions, and insertions at or near one or both breakpoints; (B) three cases in which, while the translocations appeared to be balanced, microarray analysis identified previously unrecognised imbalance on chromosomes unrelated to the translocation; (C) four cases in which the translocation breakpoints appeared simple and balanced at the resolution used. CONCLUSIONS: This high level of unexpected rearrangement complexity, if generally confirmed in the study of further patients, will have an impact on current diagnostic investigations of this type and provides an argument for the more widespread adoption of microarray analysis or other high resolution genome-wide screens for chromosome imbalance and rearrangement.

Cell Line↗

PubMed2006

Structural variation of the human genome.

There is growing appreciation that the human genome contains significant numbers of structural rearrangements, such as insertions, deletions, inversions, and large tandem repeats. Recent studies have defined approximately 5% of the human genome as structurally variant in the normal population, involving more than 800 independent genes. We present a detailed review of the various structural rearrangements identified to date in humans, with particular reference to their influence on human phenotypic variation. Our current knowledge of the extent of human structural variation shows that the human genome is a highly dynamic structure that shows significant large-scale variation from the currently published genome reference sequence.

Genetic Variation↗

PubMed2006

CGAT: a comparative genome analysis tool for visualizing alignments in the analysis of complex evolutionary changes between closely related genomes.

BACKGROUND: The recent accumulation of closely related genomic sequences provides a valuable resource for the elucidation of the evolutionary histories of various organisms. However, although numerous alignment calculation and visualization tools have been developed to date, the analysis of complex genomic changes, such as large insertions, deletions, inversions, translocations and duplications, still presents certain difficulties. RESULTS: We have developed a comparative genome analysis tool, named CGAT, which allows detailed comparisons of closely related bacteria-sized genomes mainly through visualizing middle-to-large-scale changes to infer underlying mechanisms. CGAT displays precomputed pairwise genome alignments on both dotplot and alignment viewers with scrolling and zooming functions, and allows users to move along the pre-identified orthologous alignments. Users can place several types of information on this alignment, such as the presence of tandem repeats or interspersed repetitive sequences and changes in G+C contents or codon usage bias, thereby facilitating the interpretation of the observed genomic changes. In addition to displaying precomputed alignments, the viewer can dynamically calculate the alignments between specified regions; this feature is especially useful for examining the alignment boundaries, as these boundaries are often obscure and can vary between programs. Besides the alignment browser functionalities, CGAT also contains an alignment data construction module, which contains various procedures that are commonly used for pre- and post-processing for large-scale alignment calculation, such as the split-and-merge protocol for calculating long alignments, chaining adjacent alignments, and ortholog identification. Indeed, CGAT provides a general framework for the calculation of genome-scale alignments using various existing programs as alignment engines, which allows users to compare the outputs of different alignment programs. Earlier versions of this program have been used successfully in our research to infer the evolutionary history of apparently complex genome changes between closely related eubacteria and archaea. CONCLUSION: CGAT is a practical tool for analyzing complex genomic changes between closely related genomes using existing alignment programs and other sequence analysis tools combined with extensive manual inspection.

Algorithms↗

PubMed2004

Insertion of Alzheimer's A beta 40 peptide into lipid monolayers.

The amyloid beta (A beta) peptide is the major component found in the amyloid deposits in the brains of Alzheimer's disease patients. In vitro studies have demonstrated that the aggregation of A beta can take place at three orders of magnitude lower concentrations in the presence of phospholipid molecules compared to bulk peptide studies, suggesting that membrane lipids may mediate A beta toxicity. To understand the interaction of A beta with lipid membranes, we have examined A beta 40 with anionic dipalmitoylphosphatidylglycerol (DPPG), zwitterionic dipalmitoylphosphatidylcholine (DPPC), and cationic dipalmitoyltrimethylammonium propane (DPTAP) monolayers under different subphase conditions. We have used a constant surface pressure insertion assay to assess the degree of peptide insertion into the lipids. Simultaneously, we monitored the surface morphology of the monolayers with fluorescence microscopy. We have also performed dual-probe fluorescence measurements where both the peptide and lipid are tagged with chromophores. Isotherm measurements show that A beta inserts into both DPTAP and DPPG monolayers under physiologically relevant conditions. Insertion into DPPC occurs at lipid densities below that found in a bilayer. The level of insertion is inversely proportional to the lipid packing density. Our results indicate that lipids need not be anionic to interact with A beta. Electrostatic effects involved in A beta 40-lipid interaction are discussed.

1,2-Dipalmitoylphosphatidylcholine↗

PubMedDate not supplied

[From cytogenetics to cytogenomics of adipose tissue tumors: 1. Benign adipose tissue tumors].

Benign lipomatous tumors are characterized at the genetic level by different types of chromosomal abnormalities. A rearrangement of the HMGIC (HMGA2) gene, localized in 12q15 and coding for an architectural non-histone DNA protein, is observed in a majority of solitary superficial lipomas. Alterations of HMGIC are often resulting from reciprocal translocations, such as t(3;12)(q27-28;q15) that fuses LPP with HMGIC, but a variety of chromosomal anomalies, such as deletions, inversions or insertions are also observed. Rearrangements of chromosomal regions 6p21-22, 13q, 11q13, 12q13 or others are described in approximately one third of superficial lipoma cases with abnormal karyotypes. The genes involved in these alterations remain to be determined. Lipoblastomas are pediatric neoplasms that are characterized by rearrangements of PLAG1, located in 8q11-12 whereas hibernomas, that resemble brown fat, are associated with 11q13 rearrangements together with often complex chromosomal alterations. Deletions of 13q and 16q have been identified in spindle cell lipomas. A t(11;16)(q13;p12-13) have been described in the two published karyotypes of chondroid lipomas. The chromosomal features of other rare benign lipomatous tumors, the differential diagnosis of which is occasionally difficult, such as infiltrating intra-muscular lipomas, organic deep-seated lipomas, or angiomyolipomas, myolipomas, myxolipomas are still poorly defined. Although the genetic characterization of benign lipomatous tumors has been dramatically in progress over the last ten years, many aspects remain obscure and warrant future investigations for a better comprehension of underlying molecular mechanisms.

Chromosome Aberrations↗

PubMed2002

Clustered DNA damage leads to complex genetic changes in irradiated human cells.

Densely ionizing radiations interact with DNA to cause heavily clustered sites of damage that are difficult to repair correctly. We have been able to determine for the first time the breakpoints of several very large deletions induced by densely ionizing radiation in diploid human cells and show that damage clustering is reflected in the complexity of mutations. Intra- and interchromosomal insertions and inversions occur at the sites of some large deletions. Short sequence repeats are commonly found at the breakpoints, showing that microhomologies help patch damage sites. We suggest that novel fragments found in complex rearrangements derive from other sites of radiation damage in the same cell. These transmissible molecular changes are echoed by visible chromosome rearrangements many days after irradiation and are likely to contribute significantly to the carcinogenic properties of densely ionizing radiations.

Alpha Particles↗

PubMed1984

Meiotic pairing and gametogenic failure.

In males spermatogenic impairment is associated with a wide range of chromosomal anomalies, including XYY trisomy, XO monosomy with sex reversal and heterozygosity for many structural rearrangements. Common to all these anomalies is the presence of unpaired chromosome segments during pachytene. The stage at which spermatogenic cells are lost varies markedly from one anomaly to the next. The present paper considers the possibility that there may be a common mechanism underlying these various manifestations of spermatogenic failure. An analysis of meiotic data from XYY mice had previously pointed to a causal relationship between the presence of unpaired elements at pachytene, and a failure to reach metaphase II (MII). In apparent contradiction to this is the observation that sex-reversed XO mice form reasonable numbers of round spermatids (implying progression beyond MII) despite the presence of the unpaired X. However, evidence is presented that the round spermatids of XO Sxr mice are diploid, the second meiotic division having been omitted. Most of these spermatids degenerate during spermiogenesis, but a few very abnormal sperm are produced. The female counterparts of male sterile chromosome anomalies are usually fertile, so the mechanism causing the spermatogenic failure has been presumed to be inoperative in females. However, recent work on female XO mice has revealed that although they are fertile as adults, there is nevertheless extensive oogenic failure (a 60% reduction as compared to controls) during late pachytene. It is proposed that there is a mechanism operating in both males and females which selectively removes gametogenic cells in which there has been meiotic pairing failure. In females the mechanism is not completely efficient, so that sufficient of the 'at risk' oocytes usually survive to allow fertility. In males the severity and stage of spermatogenic loss is presumed to be related to the extent of the pairing failure at pachytene. In male mammals spermatogenesis is disrupted by a wide range of karyotypic anomalies. These include XYY trisomy; XO monosomy with sex reversal; X- or Y-autosome translocations; partial or complete autosomal trisomies; heterozygosity for some autosome-autosome translocations; double heterozygosity for some Robertsonian translocations and heterozygosity for some other structural rearrangements (e.g. rings, insertions, some inversions). Common to all these anomalies is the presence of incompletely paired (synapsed) regions at pachytene. The severity of the spermatogenic impairment and the stage most affected vary widely.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2006

How genomes rearrange: genome comparison within bacteria Neisseria suggests roles for mobile elements in formation of complex genome polymorphisms.

Comparison of closely related genome sequences can provide a clue as to how macroscopic genome polymorphisms were formed through various events of recombination. However, this approach has been limited to relatively simple polymorphisms such as insertion, deletion and inversion. In the present study, we tried to extend this approach to more complex genome polymorphisms that were observed when four genome sequences of bacterial genus Neisseria were compared. The first polymorphism was an apparent translocation (ab-cd to cd-ba; a region 'ab' was translocated). The second one was a re-ordering of adjacent regions (ab-cd-ef-gh to ef-cd-ab-gh; ab, cd and ef were in reverse order). The third one was a translocation of two adjacent regions with permutation of their order (ab-cd to cd-ab elsewhere in the genome). The fourth one was a genome-wide inversion associated with a genome-specific insertion into the joints (-ab-cd- to -y-ba-x-cd-). We were able to explain their formation by only a few steps of plausible events of recombination that involved linked IS copies and prophages. Our approach would help to reconstruct a history of apparently complex genome polymorphisms in any forms of organisms and to understand genome rearrangements in the natural environments in non-model organisms.

Base Sequence↗

PubMed2004

Maintenance of a large pericentric inversion generated by the hobo transposable element in a transgenic line of Drosophila melanogaster.

The impact of the hobo transposable element in the global reorganization of the Drosophila melanogaster genome has been investigated in transgenic lines generated by the injection of hobo elements into the Hikone strain, which lacked them previously. Extensive surveys of transgenic lines followed for 250 generations have identified 13 inversions with hobo inserts at most breakpoints. One of these inversions is pericentric on chromosome 2. It has been maintained in the line where it was discovered and in several sublines at frequencies from 0.19 to 0.45, generating stable chromosomal polymorphisms, similar to cosmopolitan paracentric inversions in natural populations. Individuals homozygous for this inversion were viable and fertile, allowing the creation of a new homozygous strain.

Animals↗

PubMed1991

An optimized multislice acquisition sequence for the inversion-recovery MR imaging.

An optimized multislice data acquisition scheme for inversion-recovery MR imaging is proposed and experimental results are presented. In this new scheme, instead of forming a set of multislice inversion-recovery sequences in series for a given phase encoding step, 180 degrees inversion pulses corresponding to different slices are interwoven with the spin echo data acquisition sequence in an optimal way depending on the desired inversion-recovery time. For example, between the 180 degrees inversion RF pulse and the spin-echo imaging sequence, a number of imaging and inversion sequences are inserted with different slice combinations, i.e., long inversion-recovery time is effectively utilized for the other slice pre-inversion and data acquisition. With the optimized sequence, imaging time has been reduced by as much as a factor of four compared with the existing methods.

Brain↗

PubMed2004

Transposon mutagenesis of the obligate intracellular pathogen Rickettsia prowazekii.

Genetic analysis of Rickettsia prowazekii has been hindered by the lack of selectable markers and efficient mechanisms for generating rickettsial gene knockouts. We have addressed these problems by adapting a gene that codes for rifampin resistance for expression in R. prowazekii and by incorporating this selection into a transposon mutagenesis system suitable for generating rickettsial gene knockouts. The arr-2 gene codes for an enzyme that ADP-ribosylates rifampin, thereby destroying its antibacterial activity. Based on the published sequence, this gene was synthesized by PCR with overlapping primers that contained rickettsial codon usage base changes. This R. prowazekii-adapted arr-2 gene (Rparr-2) was placed downstream of the strong rickettsial rpsL promoter (rpsL(P)), and the entire construct was inserted into the Epicentre EZ::TN transposome system. A purified transposon containing rpsL(P)-Rparr-2 was combined with transposase, and the resulting DNA-protein complex (transposome) was electroporated into competent rickettsiae. Following selection with rifampin, rickettsiae with transposon insertions in the genome were identified by PCR and Southern blotting and the insertion sites were determined by rescue cloning and inverse PCR. Multiple insertions into widely spaced areas of the R. prowazekii genome were identified. Three insertions were identified within gene coding sequences. Transposomes provide a mechanism for generating random insertional mutations in R. prowazekii, thereby identifying nonessential rickettsial genes.

Animals↗

PubMed2004

[Paracentric inversions of human chromosomes and their risks].

The incidence of paracentric inversions in the general population has not been clearly established, it ranges from 0.09 to 0.49/1,000. Homologue pairing during melosis in a paracentric-inversion heterozygote is maximized by the formation of an inversion loop. If a crossing-over occurs within this loop, dicentric and acentric chromosomes are formed. Resulting gametes can have variety of duplications and deficiencies and give a non-viable progeny. One of the exceptions to the rule is a mutation event "U loop recombination". From U-loop event a monocentric recombinant chromosome can arise by an abnormal process, which involves chromatid breakage and reunion. Most of the paracentric inversions in man are harmless and the risk of heterozygotes having a child with an unbalanced karyotype is relatively low. In carriers of an accidentally discovered paracentric inversion, amniocentesis is optional. However, in some cases, it is difficult to distinguish between a paracentric inversion and paracentric insertion--the risk of the insertion is about 15%. When a de novo inversion is detected in amniotic fluid, the overall risk for two-break rearrangements is 6.7%.

Chromosome Inversion↗

PubMed2002

Inversions over the terminus region in Salmonella and Escherichia coli: IS200s as the sites of homologous recombination inverting the chromosome of Salmonella enterica serovar typhi.

Genomic rearrangements (duplications and inversions) in enteric bacteria such as Salmonella enterica serovar Typhimurium LT2 and Escherichia coli K12 are frequent (10(-3) to 10(-5)) in culture, but in wild-type strains these genomic rearrangements seldom survive. However, inversions commonly survive in the terminus of replication (TER) region, where bidirectional DNA replication terminates; nucleotide sequences from S. enterica serovar Typhimurium LT2, S. enterica serovar Typhi CT18, E. coli K12, and E. coli O157:H7 revealed genomic inversions spanning the TER region. Assuming that S. enterica serovar Typhimurium LT2 represents the ancestral genome structure, we found an inversion of 556 kb in serovar Typhi CT18 between two of the 25 IS200 elements and an inversion of about 700 kb in E. coli K12 and E. coli O157:H7. In addition, there is another inversion of 500 kb in E. coli O157:H7 compared with E. coli K12. PCR analysis confirmed that all S. enterica serovar Typhi strains tested, but not strains of other Salmonella serovars, have an inversion at the exact site of the IS200 insertions. We conclude that inversions of the TER region survive because they do not significantly change replication balance or because they are part of the compensating mechanisms to regain chromosome balance after it is disrupted by insertions, deletions, or other inversions.

Chromosome Inversion↗

PubMed1994

Amino acid sequence homology between Piv, an essential protein in site-specific DNA inversion in Moraxella lacunata, and transposases of an unusual family of insertion elements.

Deletion analysis of the subcloned DNA inversion region of Moraxella lacunata indicates that Piv is the only M. lacunata-encoded factor required for site-specific inversion of the tfpQ/tfpI pilin segment. The predicted amino acid sequence of Piv shows significant homology solely with the transposases/integrases of a family of insertion sequence elements, suggesting that Piv is a novel site-specific recombinase.

Amino Acid Sequence↗

PubMed1980

Molecular engineering of the herpes simplex virus genome: insertion of a second L-S junction into the genome causes additional genome inversions.

We have developed a technique for the insertion of any DNA fragment into the herpes simplex virus (HSV) genome at specific sites. This technique was used to resolve a specific problem concerning the isomerization of the HSV genome. Briefly, HSV DNA consists of four isomers differing in the orientation of two covalently linked components, L and S, relative to each other. Each component consists of unique sequences flanked by inverted repeats. To determine whether the isomerization of HSV DNA is the result of generalized recombinatin between homologous reiterated sequences in the inverted repeats or the result of site-specific recombination, we constructed plasmids in which DNA fragments derived from various regions of the viral genome were inserted in both orientations into the thymidine kinase gene, rendering it nonfunctional. The HSV DNA sequences in the plasmids were then recombined into the viral genome, and viral recombinants were selected for their thymidine kinase-deficient phenotype. The insertion of these fragments by homologous recombination was highly efficient in that all the viral clones isolated contained the inserted fragment at the expected location. The only fragments that promoted additional inversions of the viral genome were those spanning the junction between the L and S components. Furthermore, analysis of isomers formed by these recombinants indicates that the inversions occur only when sequences in the inserted fragment are in inverted orientation in relation to homologous sequences at the termini or at the authentic junction.

Base Sequence↗

PubMed2002

Human l1 retrotransposition is associated with genetic instability in vivo.

Retrotransposons have shaped eukaryotic genomes for millions of years. To analyze the consequences of human L1 retrotransposition, we developed a genetic system to recover many new L1 insertions in somatic cells. Forty-two de novo integrants were recovered that faithfully mimic many aspects of L1s that accumulated since the primate radiation. Their structures experimentally demonstrate an association between L1 retrotransposition and various forms of genetic instability. Numerous L1 element inversions, extra nucleotide insertions, exon deletions, a chromosomal inversion, and flanking sequence comobilization (called 5' transduction) were identified. In a striking number of integrants, short identical sequences were shared between the donor and the target site's 3' end, suggesting a mechanistic model that helps explain the structure of L1 insertions.

5' Flanking Region↗