Structure of IS elements.
description
Transcript of Structure of IS elements.
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Structure of IS elements.
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These and other transposons have inverted terminal repeats (numerals) and are flanked by direct repeats of host DNA target sequences (letters).
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A model for the generation of direct repeats of the target sequence by
transposon insertion.
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Properties of Some Insertion Elements.
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A map of transposon Tn3.
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Total size 4957 bp. Inverted terminal repeats 38 bp each
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A composite transposon.
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The IS-like modules may have either (a) direct or (b) inverted relative orientations.
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Electron micrograph of a single-stranded circular DNA containing
a transposon.
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The cut-and-paste transposition mechanism catalyzed by Tn5
transposase.
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Cut and paste transposition
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How the cut is performed
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Comparison of transposition pathways.
Grey segments represent transposable DNA elements. Small arrows indicate phosphodiester bond breakage. Solid and dotted lines represent donor and target DNA, respectively
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X-Ray structure of Tn5 transposase.
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in complex with a 20-bp DNA containing the OE sequence
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Replicative transposition.
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This type of transposition inserts a copy of the transposon at the target site while another copy remains at the donor site.
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A cointegrate.
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This structure forms by the fusion of two plasmids, one carrying a transposon, such that both junctions of the original plasmid are spanned by transposons with the same orientation (arrows).
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A model for transposition involving the intermediacy of a cointegrate.
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Here more lightly shaded bars represent newly synthesized DNA.
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Chromosomal rearrangement via recombination.
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(a) The inversion of a DNA segment between two identical transposons with inverted orientations.
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Chromosomal rearrangement via recombination..
(b) The deletion of a DNA segment between two identical transposons with the same orientation
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The mechanism of phase variation in Salmonella.
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hin codes for Hin DNA invertase
hix : Two sites, closely related, 26 bp (2 x 12 bp imperfect inverted repeats separated by 2 bp)
H1, H2: Genes for two antigenically distinct flagellin proteins
rh1: Gene for H1 gene repressor
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Størrelse av genomer
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Sammensetning av genomet
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Repetitive DNA
Iinterspersedinterspersed in tandemin tandem
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Moderately Repetitive Sequences in the Human Genomea
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Klasser av intersperserte repetisjoner i det humane genom
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Elementer i det humane genom som kan transposeres på en RNA-formidlet måte
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Alu elementsLength = ~300 bp
Repetitive: > 1,000,000 times in the human genome
Constitute >10% of the human genome
Found mostly in intergenic regions and introns
Propagate in the genome through retroposition (RNA intermediates).
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Evolution of Alu elements
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Alu elements can be divided into subfamilies
The subfamilies are The subfamilies are distinguished by distinguished by ~16 diagnostic ~16 diagnostic positions.positions.
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Transposisjonering av et typisk humant Alu-element
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Alu-elementer hos primater
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Alu sequences in the globin gene cluster
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Gene sequences of (a) retroviruses and(b) the Ty1 retrotransposon from yeast.
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Naturally occuring methylated bases in DNA
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The catalytic mechanism of 5-methylcytosine methyltransferases
(m5C-MTases).
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X-Ray structure of M.HhaIP
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in complex with S-adenosylhomocysteine and a duplex 13-mer DNA containing a methylated f5C residue at the enzyme’s target site.
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Maintenance methylation.
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CpG-frekvens og CpG-øyer
The typical density of CpG doublets in mammalian DNA is ~1/100 bp, as seen for a -globin gene. In a CpG-rich island, the density is increased to >10 doublets/100 bp. The island in the APRT gene starts ~100 bp upstream of the promoter and extends ~400 bp into the gene. Each vertical line represents a CpG doublet.
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CpG-øyer
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Vedlikeholdsmetylering
Ved maintenance-metylering induserer metyleringsmønsteret i en parental DNA-tråd det tilsvarende metyleringsmønster i den komplementære tråden. Slik kan et stabilt metyleringsmønster opprettholdes i en cellelinje
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CpG – underrepresentert i genomet
The CpG doublet occurs in vertebrate DNA at only ~20% of the frequency that would be expected from the proportion of G·C base pairs. (this is because CpG doublets are methylated on C, and spontaneous deamination of methyl-C converts it to T, introducing a mutation that removes the doublet.) In certain regions, however, the density of CpG doublets reaches the predicted value; in fact, it is increased by 10× relative to the rest of the genome. The CpG doublets in these regions are unmethylated
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Cytosin, metylcytosin og tymin
Tme
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Evolusjon av CpG-øyer: en mulig mekanisme
Ancestralt eukaryot genom med metylering av C i CpG, bortsett fra i visse genassosierte områder
Metylerte CpG muteres gradvis til TpG eller CpA, mens umetylerte CpG forblir
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Microsatellite terminology
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Trinucleotide expansion diseasesTABLE 1
DISEASES OF TRINUCLEOTIDE REPEATS
NAME OF THE DISEASE SEQUENCE OF THE REPEAT
LOCATION OF THE REPEAT
Fragile site 11B Fragile X syndrome
CGG EXON
Dentatorubral-pallidoluysian atrophy Haw river syndrome Huntington's disease Machado-Joseph disease Spinal and Bulbar muscular dystrophy Spinocerebellar ataxia type 1
CAG EXON
Myotonic dystrophy CTG EXON
Friedrich's ataxia GAA INTRON
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The loop-out mechanism for the alteration of the number of consecutive triplet
repeats in DNA through its replication.
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