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Results for “insertion, inversion”

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PubMed1990

Complex cytogenetic changes in benign neoplasms. Report of six lipomas.

We report the detailed cytogenetic findings from short-term cultures of six lipomas with complex chromosomal abnormalities. In all six cases, the abnormality occurred in two stages; an initial inversion, translocation, or insertion of the involved chromosome(s) followed by a subsequent rearrangement of the resultant derivative chromosome(s). A striking feature of these rearrangements was the consistent involvement of bands q13 - q14 on chromosome 12 in all the abnormalities. This region has been shown to be specifically rearranged in most of the lipomas studied. The other chromosomes involved in the rearrangements were chromosomes 1 in four cases, 5 and 9 in two cases each, and 2, 3, 4, 7, and 10 in one case each. Our findings and published findings show that, with a few exceptions, benign tumors that were previously considered cytogenetically normal, are characterized not only by specific numerical and structural changes but may also contain complex chromosome rearrangements that are generally considered a hallmark of advanced malignancy. In benign tumors, this suggests that the genes at the region of the breakpoints may represent proliferation-related genes or that benign tumors with such complex aberrations represent neoplasms potentially capable of undergoing transformation to malignancy, or both.

Adult↗

PubMed2004

Complete mitochondrial DNA sequence of the sea-firefly, Vargula hilgendorfii (Crustacea, Ostracoda) with duplicate control regions.

The primary structure of the mitochondrial genome of the bioluminescent crustacean, Vargula hilgendorfii, the sea-firefly (Arthropoda, Crustacea, Ostracoda), has sequenced using the transposon Tn5. The genome (15,923 bp) contains the same 37 genes (two ribosomal RNAs, 22 transfer RNAs, and 13 protein-coding genes) found in other Arthropoda. Interestingly, duplicate control regions (fragments of 778 and 855 bp) and triplicate short repeat sequences (fragments of 49 bp) occur. The AT composition of the protein-coding genes is lower than the published complete mitochondrial genomes within the Arthropoda. For gene arrangement, 13 transfer RNA genes and two protein-coding genes have moved and inserted directly or inversely relative to the typical Arthropoda order.

Animals↗

PubMed1986

Sequence homologies of glucose-dehydrogenases of Bacillus megaterium and Bacillus subtilis.

The sequence homologies of the glucose dehydrogenase subunits of B. megaterium and B. subtilis are compared. From the known B. megaterium aminoacid sequence and the base sequence of the cloned B. subtilis structural gene we predict the B. megaterium structural glucose dehydrogenase gene. Assuming the minimal mutational changes to convert one gene into the other 23 transitions, 30 transversions, 1 inversion, 3 insertion-deletions, but no frameshifts are postulated necessary to interconvert the structural genes. The homology of both enzyme subunits of 85% reflects the close evolutionary distance between B. subtilis and B. megaterium.

Amino Acid Sequence↗

PubMed2001

Mobilization of a Drosophila transposon in the Caenorhabditis elegans germ line.

Transposons have been enormously useful for genetic analysis in both Drosophila and bacteria. Mutagenic insertions constitute molecular tags that are used to rapidly clone the mutated gene. Such techniques would be especially advantageous in the nematode Caenorhabditis elegans, as the entire sequence of the genome has been determined. Several different types of endogenous transposons are present in C. elegans, and these can be mobilized in mutator strains (reviewed in ref. 1). Unfortunately, use of these native transposons for regulated transposition in C. elegans is limited. First, all strains contain multiple copies of these transposons and thus new insertions do not provide unique tags. Second, mutator strains tend to activate the transposition of several classes of transposons, so that the type of transposon associated with a particular mutation is not known. Here we demonstrate that the Drosophila mariner element Mos1 can be mobilized in C. elegans. First, efficient mobilization of Mos1 is possible in somatic cells. Second, heritable insertions of the transposon can be generated in the germ line. Third, genes that have been mutated by insertion can be rapidly identified using inverse polymerase chain reaction. Fourth, these insertions can subsequently be remobilized to generate deletion and frameshift mutations by imperfect excision.

Animals↗

PubMed1998

Double-strand break repair mediated by DNA end-joining.

DNA double-strand breaks formed by ionizing irradiation or other stresses are repaired by homologous recombination or DNA end-joining. This review focuses on the mechanism of double-strand break repair mediated by DNA end-joining, in which many factors have recently been identified. After DNA double-strand breakage, DNA end-joining takes place between the DNA ends that have nonhomologous sequences or very short regions ofhomology. The broken DNA is repaired if the DNA end-joining occurs in the same molecule, while it causes chromosome aberrations such as deletions, insertions, translocations and inversions if it occurs between different molecules. Rad50 and its relatives, Ku-proteins, DNA ligase VI and silencing factors, are involved in DNA end-joining in yeast and mammalian cells. These findings led us to propose a model in which the formation of a heterochromatin-like complex at broken ends is an important element in DNA end-joining.

Animals↗

PubMed1980

Site specificity of mutations arising in dysgenic hybrids of Drosophila melanogaster.

Mutations arising in dysgenic hybrids of Drosophila melanogaster were collected in the zeste-white region of the X chromosome. A preponderance of the mutations affected the zw1 locus; many of these were asociated with structural abnormalities including inversions, deficiencies, and insertions in the 3A3-4 region of the polytene chromosome map. The extreme sensitivity of the zw1 locus to the mutator activity of dysgenic hybrids contrasted with the apparent insensitivity of the zw2 locus. Other loci in the zeste-white region were weakly sensitive to the mutator activity. Insertions of two and six bands were seen between bands 3A4 and 3A6 in the chromosomes of one of the zw1 mutant stocks examined. Another insertion was detected at position 2F4-5 in a different stock. Many of the mutant chromosome were evidently unstable, as judged by secondary breakage in other parts of the X chromosome. The cytogenetic data are consistent with the idea that mutations arising in dysgenic hybrids are caused by transposable elements which insert preferentially at certain sites on the chromosomes.

Animals↗

PubMed1982

Cloned ural locus of Schizosaccharomyces pombe propagates autonomously in this yeast assuming a polymeric form.

DNA segments cloned from Schizosaccharomyces pombe by the ability to complement Escherichia coli pyrB mutations are shown to complement a ural mutation in S. pombe, thereby demonstrating that ural is the structural gene for aspartate transcarbamylase of S. pombe. Further, such segments combined with parts or all of pBR322 are shown to be capable of autonomous propagation in S. pombe. This suggests the existence of an autonomously replicating sequence (ars) in the vicinity of ural. Unlike the TRP1 segment cloned from Saccharomyces cerevisiae [Struhl, K., Stinchcomb, D. T., Scherer, S. & Davis, R. W. (1979) Proc. Natl. Acad. Sci. USA 76, 1035-1039], plasmids carrying the ural locus do not multiply as monomers but assume a polymeric form as large as a decamer to an icosamer in the yeast. Monomers are tandemly arranged in the polymer. Inversion of an inserted fragment or insertion of another segment into a competent plasmid greatly decreases the efficiency of such transformation, implying a role of the tertiary structure of the plasmids in the establishment of transformation of this kind.

Ascomycota↗

PubMed2004

Statistical detection of chromosomal homology using shared-gene density alone.

MOTIVATION: Over evolutionary time, various processes including point mutations and insertions, deletions and inversions of variable sized segments progressively degrade the homology of duplicated chromosomal regions making identification of the homologous regions correspondingly difficult. Existing algorithms that attempt to detect homology are based on shared-gene density and colinearity and possibly also strand information. RESULTS: Here, we develop a new algorithm for the statistical detection of chromosomal homology, CloseUp, which uses shared-gene density alone to fully exploit the observation that relaxing colinearity requirements in general is beneficial for homology detection and at the same time optimizes computation time. CloseUp has two components: the identification of candidate homologous regions followed by their statistical evaluation using Monte Carlo methods and data randomization. Using both artificial and real data, we compared CloseUp with two existing programs (ADHoRe and LineUp) for chromosomal homology detection and found that in general CloseUp compares favorably. AVAILABILITY: CloseUp and supplementary information are available at http://www.igb.uci.edu/servers/cgss.html CONTACT: pfbaldi@ics.uci.edu.

Algorithms↗

PubMed2026

The value of structural variants to conservation genomics in the pangenome era.

Structural variants (SVs) comprise an axis of genetic diversity with strong consequences for phenotype and fitness, making them a potentially important target for conservation genomics. Here, we review how and why SVs can play a role in conservation genomics; the different types of SVs and how they can affect phenotype; and how pangenomes and long-read sequencing are illuminating their evolution in populations, including small populations and those of conservation concern. SVs comprise multinucleotide mutations including insertions, deletions, transpositions, inversions, and other multinucleotide mutations, often overlapping genes and other functional genome regions. As a result, SVs often play important roles in phenotypic evolution and local adaptation and can contribute substantially to genetic load in inbred populations. However, our understanding of the factors influencing SV diversity in populations is still in its infancy and is complicated by the vast range of sizes, effects, and mechanisms of formation of these mutations. We argue that SVs are an important axis of genetic diversity which should be characterized alongside more traditional metrics of genetic diversity in conservation contexts. There are a number of analytical challenges to detecting and studying SVs, but analyses aimed at understanding the role of SVs in inbreeding load and population health are rapidly becoming realizable goals, accelerated by new technologies and analytical approaches. New tools, including population-scale long-read sequencing and pangenome approaches, are beginning to make SVs accessible in ways which can be readily applied in conservation settings.

Genomic Structural Variation↗

PubMed2003

Molecular evolution of insertions and deletion in the chloroplast genome of silene.

Insertions, deletions, and inversions in the chloroplast genome of higher plants have been shown to be extremely useful for resolving phylogenetic relationships both between closely related taxa and among more basal lineages. Introns and intergenic spacers from the chloroplast genome are now increasingly used for phylogenetic and population genetic studies of populations from a single species, and it is therefore interesting to know whether indels can provide useful data and hence increase the power of intraspecific studies. Here, we show that indels in three cpDNA intergenic spacers and one cpDNA intron for two species of Silene evolve at slightly higher rates than base pair substitutions. Repeat indels appear to have the highest rate of evolution and are thus more prone to homoplasy. We show that coded indel data have high information content for phylogenetic analysis, and indels thus provide useful information to infer phylogenetic relationships at the intraspecific level.

Chloroplasts↗

PubMed2004

Transcriptional control of RAD51 expression in the ciliate Tetrahymena thermophila.

The expression of Rad51p, a DNA repair protein that mediates homologous recombination, is induced by DNA damage and during both meiosis and exconjugant development in the ciliate Tetrahymena thermophila. To completely investigate the transcriptional regulation of Tetrahymena RAD51 expression, reporter genes consisting of the RAD51 5' non-translated sequence (5' NTS) positioned upstream of either the firefly luciferase or green fluorescent protein coding sequences have been targeted for recombination at the macronuclear btu1-1 (K350M) locus of T. thermophila strain CU522. Expression from RAD51-luciferase reporter constructs has been directly quantified from transformant whole cell lysates. Luciferase is induced to maximum levels in transformants harboring the full-length RAD51-luciferase reporter gene following exposure to DNA damaging UV irradiation. A series of truncations, deletions, insertions, substitutions and inversions of the RAD51 5' NTS have led to the identification of three distinct transcriptional promoter elements. The first of these sequence elements is required for basal levels of transcription. The second modulates expression in the absence of DNA damage, whereas the third ensures increased RAD51 transcription in response to DNA damage and during meiosis. Tetrahymena RAD51 is tightly regulated through these transcriptional elements to produce the appropriate expression during conjugation, and in response to DNA damage.

Animals↗

PubMed2005

Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery.

The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately 700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features.

DNA Transposable Elements↗

PubMed2004

Mos as a tool for genome-wide insertional mutagenesis in Caenorhabditis elegans: results of a pilot study.

The sequence of the Caenorhabditis elegans genome contains approximately 19 000 genes. Available mutants currently exist for <20% of these genes. The existence of a Mos-based inducible transposon system in C.elegans could theoretically serve as a tool to saturate the genome with insertions. We report here the results of a pilot study aimed at assaying this strategy. We generated 914 independent random Mos insertions and determined their location by inverse PCR. The distribution of the insertions throughout the genome does not reveal any gross distortion, with the exception of a major hotspot on chromosome I (rDNA locus). Transposons are evenly distributed between the genic and intergenic regions. Within genes, transposons insert preferentially into the introns. We derived the consensus target site for Mos in C.elegans (ATATAT), which is common to Tc1, another mariner element. Finally, we assayed the mutagenic properties of insertions located in exons by comparing the phenotype of homozygous strains to that of known mutations or RNAi of the same gene. This pilot experiment shows that a Mos-based approach is a viable strategy that can contribute to the constitution of genome-wide collections of identified C.elegans mutants.

Animals↗

PubMed2002

Evolution of multi-gene segments in the mutS-rpoS intergenic region of Salmonella enterica serovar Typhimurium LT2.

The nucleotide sequence of the 12.6 kb region between the mutS and rpoS genes of Salmonella enterica serovar Typhimurium LT2 (S. typhimurium) was compared to other enteric bacterial mutS-rpoS intergenic regions. The mutS-rpoS region is composed of three distinct segments, designated HK, O and S, as defined by sequence similarities to contiguous ORFs in other bacteria. Inverted chromosomal orientations of each of these segments are found between the mutS and rpoS genes in related ENTEROBACTERIACEAE: The HK segment is distantly related to a cluster of seven ORFs found in Haemophilus influenzae and a cluster of five ORFs found between the mutS and rpoS genes in Escherichia coli K-12. The O segment is related to the mutS-rpoS intergenic region found in E. coli O157:H7 and Shigella dysenteriae type 1. The third segment, S, is common to diverse Salmonella species, but is absent from E. coli. Despite the extensive collinearity and conservation of the overall genetic maps of S. typhimurium and E. coli K-12, the insertions, deletions and inversions in the mutS-rpoS region provide evidence that this region of the chromosome is an active site for horizontal gene transfer and rearrangement.

Adenosine Triphosphatases↗

PubMed2025

Defining and cataloging variants in pangenome graphs.

Structural variation causes some human haplotypes to align poorly with the linear reference genome, leading to 'reference bias'. A pangenome reference graph could ameliorate this bias by relating a sample to multiple reference assemblies. However, this approach requires a new definition of a 'genetic variant.' We introduce a definition of pangenome variants and a method, pantree, to identify them. Our approach involves a pangenome reference tree which includes all nodes (sequences) of the pangenome graph, but only a subset of its edges; non-reference edges are variant edges. Our variants are biallelic and have well-defined positions. Analyzing the Minigraph-Cactus draft human pangenome reference graph, we identified 29.6 million genetic variants. Most variants (99.2%) are small, and most small variants (73.9%) are SNPs. 3.5 million variants (11.7%) have a reference allele which is not on GRCh38; these variants are difficult to detect without a pangenome reference, or with existing pangenome-based approaches. They tend to be embedded within tangled, multiallelic regions. We analyze two medically relevant regions, around the HLA-A and RHD genes, identifying thousands of small variants embedded within several large insertions, deletions, and inversions. We release an open-source software tool together with a VCF variant catalogue.

Journal Article↗

PubMed2000

Extensive duplication and reshuffling in the Arabidopsis genome.

Systematic analysis of the Arabidopsis genome provides a basis for detailed studies of genome structure and evolution. Members of multigene families were mapped, and random sequence alignment was used to identify regions of extended similarity in the Arabidopsis genome. Detailed analysis showed that the number, order, and orientation of genes were conserved over large regions of the genome, revealing extensive duplication covering the majority of the known genomic sequence. Fine mapping analysis showed much rearrangement, resulting in a patchwork of duplicated regions that indicated deletion, insertion, tandem duplication, inversion, and reciprocal translocation. The implications of these observations for evolution of the Arabidopsis genome as well as their usefulness for analysis and annotation of the genomic sequence and in comparative genomics are discussed.

Arabidopsis↗

PubMed2004

Molecular cytogenetic characterization of multiple intrachromosomal rearrangements of chromosome 2q in a patient with Waardenburg's syndrome and other congenital defects.

At 6 years of age, a boy with bilateral sensorineural deafness, lateral displacement of inner canthi, a bulbous nasal tip, synophrys, and cryptorchidism was clinically diagnosed as having Waardenburg's syndrome type I (WS-1). In addition, he had a lumbar spina bifida with hydrocephalus shunted on the second day of life and severe mental retardation with a head circumference at the fifth percentile. Neither parent showed signs of WS-1, and the family history was negative. Because of the WS-1 features, attention was focused on the PAX3 location in 2q, at which time a de novo paracentric inversion of 2q23-q37.1 was noted. Subsequent high-resolution chromosome analysis 8 years later indicated a complex rearrangement involving regions 2q31-q35 and 2q13-q21. Whole chromosome painting and high-resolution comparative genomic hybridization yielded negative results for any translocation, duplication, or deletion of any chromosome segments. Sequencing of the PAX3 gene yielded no detectable mutation. Fluorescent in situ hybridization (FISH) studies with human BAC clones revealed five breakpoints in chromosome 2q resulting in two paracentric inversions and one insertion, the karyotype being interpreted as 46,XY,der(2)inv(2)(q13q21)inv(2)(q21q24.2)ins(2)(q24.2q33q35). In this extremely rare chromosomal rearrangement, the FISH result showed a breakpoint at 2q35 being proximal to and without involvement of the PAX3 gene. While further studies continue, possible interpretations include involvement of a regulatory gene(s) for PAX 3 and other genes at the other breakpoints related causally to the spina bifida and mental retardation.

Adolescent↗

PubMed1995

Lipopolysaccharide with an altered O-antigen produced in Escherichia coli K-12 harbouring mutated, cloned Shigella flexneri rfb genes.

Cloning of the rfb genes of Shigella flexneri 2a into Escherichia coli K-12 strain DH1 results in the synthesis of lipopolysaccharides (LPS) with an O-antigen chain having type antigen IV and group antigens 3,4. During genetic studies of these rfb genes in E. coli K-12, we observed that strains harbouring plasmids with certain mutations (inversion and transposon insertions) which should have blocked O-antigen synthesis nevertheless still produced LPS with O-antigen chains. These LPS migrated differently on silver-stained SDS-polyacrylamide gels, compared with the LPS produced by wild-type rfb genes, and the group 3,4 antigens were barely detectable, suggesting that the O-antigen was altered. Investigation of the genetic determinants for production of the altered O-antigen/LPS indicated that: (i) these LPS are produced as a result of mutations which are either polar on rfbF or inactivate rfbF; (ii) the rfbX gene product (or a similar protein in the E. coli K-12 rfb region) is needed for production of the altered O-antigen in the form of LPS; (iii) the rfbG gene product is required for the production of both the parental and altered LPS; (iv) the dTDP-rhamnose biosynthesis genes are required. Additionally, an E. coli K-12 gene product(s) encoded outside the rfb region also contributes to production of the O-antigen of the altered LPS. An antiserum raised to the altered LPS from strain DH1(pPM2217 (rfbX::Tn1725)) was found to cross-react with nearly all S. flexneri serotypes, and with the altered LPS produced by other DH1 strains harbouring plasmids with different rfb mutations, as described above. The reactivity of the altered LPS with a panel of monoclonal antibodies specific for various S. flexneri O-antigen type and group antigens demonstrated that their O-antigen components were closely related to that of S. flexneri serotype 4. The RfbF and RfbG proteins were shown to have similarity to rhamnose transferases, and we identified a motif common to the N-termini of 6-deoxy-hexose nucleotide sugar transferases. We propose that the E. coli K-12 strains harbouring the mutated S. flexneri rfb genes produce LPS with a hybrid O-antigen as a consequence of inactivation of RfbF and complementation by an E. coli K-12 gene product. Analysis of the genetic and immunochemical data suggested a possible structure for the O-antigen component of the altered LPS.

Amino Acid Sequence↗