A variable tandem repeat locus mapped to chromosome band 10q26 is amplified and rearranged in leukocyte DNAs of two cancer patients

Colb, Mark; Yang‐Feng, Teresa L.; Francke, Uta; Mermer, Brion; Parkinson, David; Krontiris, Theodore G.

doi:10.1093/nar/14.20.7929

Cited by 15 publications

(9 citation statements)

References 15 publications

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“…We screened a human genomic library at low stringency and isolated one recombinant phage, 4.1. This phage did contain a VTR with approximately 25 copies of a 35-bp monomer (8). The 4.1 monomer contained a 14-of 15-bp match with one region of the HRASI VTR monomer (see below).…”

Section: Resultsmentioning

confidence: 99%

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A family of short, interspersed repeats is associated with tandemly repetitive DNA in the human genome.

Mermer¹,

Colb²,

Krontiris³

1987

Proc. Natl. Acad. Sci. U.S.A.

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A family of short, interspersed repeats in the human genome, designated the Mst II family, is described. The canonical structure of the repeat consists of a 220-base-pair (bp) left arm joined to a 160-bp right arm by a 39-bp junction sequence. The right arm is absent in some isolates. Some homology with the "0" and "THE" (transposon-like element) families of repeats was observed, suggesting that the Mst II elements could be a subgroup of a SINE superfamily. The 39-bp junction sequence is tandemly repeated in one of our clones.The association of tandemly repetitive sequences with Mst H elements or the putative superfamily is probably nonrandom; a search of DNA sequence data bases revealed that approximately 80 bp of the Mst II left arm occurs immediately adjacent to the tandem repeat that comprises the human homologue to the BK virus enhancer. The fortuitous occurrence of a gene duplication event involving an Mst II repeat has allowed us to estimate a mutation rate for human DNA.The structural basis for genetic variation in many highly polymorphic regions of the human genome is the tandem repetition of 14-to 65-base-pair (bp) nucleotide sequences (1-5). The variable tandem repeat (VTR) approximately 1.5 kilobases (kb) downstream from the cellular homologue of the Harvey rat sarcoma virus oncogene, c-Ha-rasl (HRASI in human gene nomenclature) (2), generates at least 25 allelic forms in which a 28-bp consensus sequence is reiterated 30-100 times (6, 7). Many of the rare alleles at this locus are detected only in cancer patients (6, 7). Since such hyperallelism might be exploited in quantitating the degree of genomic instability in human populations, we have sought to identify other regions related to the HRASI VTR.As a result of this search, we identified a highly polymorphic region distinct from the HRASI VTR (7). Sequence analysis of this region, designated 4.1, revealed the head-totail aggregation of a 35-bp monomer (8). When 4.1 was used as a probe for other polymorphic clones, 0.5-1% of the phage in a human DNA library were recognized by in situ plaque hybridization. We report here the characterization of the repeat family responsible for this result, including the observation of its intimate association with VTRs. MATERIALS AND METHODSGenomic Library, Vectors, and Bacterial Strains. A human genomic library in Charon 4A (9) was kindly provided by Tom Maniatis. It was propagated in Escherichia coli LE392. Phage lysates were also prepared from this strain. Plasmid subclones were propagated in HB101 or JM83 with pBR322 or pUC9, respectively. DNA Transfer Hybridization. DNA was transferred to nitrocellulose filters (Schleicher & Schuell) by methods previously described for phage plaques (10) or agarose gels (11). Low-stringency hybridization was performed at 50'C in 5x SET buffer (1x SET buffer is 0.15 M NaCl/10 mM EDTA/10 mM Tris, pH 7.5) and 0.5% NaDodSO4. Three or four washes were performed at 37°C (unless otherwise stated) in 2x SET buffer/0.5% NaDodSO4 for 30 min each. The radioactive probe was prepar...

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Section: Resultsmentioning

confidence: 99%

“…Sequence analysis of this region, designated 4.1, revealed the head-totail aggregation of a 35-bp monomer (8). When 4.1 was used as a probe for other polymorphic clones, 0.5-1% of the phage in a human DNA library were recognized by in situ plaque hybridization.…”

mentioning

confidence: 99%

A family of short, interspersed repeats is associated with tandemly repetitive DNA in the human genome.

Mermer¹,

Colb²,

Krontiris³

1987

Proc. Natl. Acad. Sci. U.S.A.

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“…On the basis of the results obtained with VNTR core sequence probes, we anticipate that two-dimensional DNA fingerprinting can be applied in a number of different areas in genetic research. The method should be useful in the analysis of large parts of the genome for measuring mutation frequencies (15) and for detecting putative changes in VNTR loci or other unstable DNA regions during tumor induction and growth (9,16) or during aging (17). Two-dimensional DNA fingerprinting can be used in association studies and to extend and improve linkage analysis and gene mapping.…”

Section: Discussionmentioning

confidence: 99%

Two-dimensional DNA fingerprinting of human individuals.

Uitterlinden

Slagboom

Knook

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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The limiting factor in the presently available techniques for the detection of DNA sequence variation in the human genome is the low resolution of Southern blot analysis. To increase the analytical power of this technique, we applied size fractionation of genomic DNA restriction fragments in conjunction with their sequence-dependent separation in denaturing gradient gels; the two-dimensional separation patterns obtained were subsequently transferred to nylon membranes. Hybridization analysis using minisatellite core sequences as probes resulted in two-dimensional genomic DNA fingerprints with a resolution of up to 625 separated spots per probe per human individual; by conventional Southern blot analysis, only 20-30 bands can be resolved. Using the twodimensional DNA fingerprinting technique, we demonstrate in a small human pedigree the simultaneous transmission of 37 polymorphic fragments (out of 365 spots) for probe 33.15 and 105 polymorphic fragments (out of 625 spots) for probe 33.6. In addition, a mutation was detected in this pedigree by probe 33.6. We anticipate that this method will be of great use in studies aimed at (i) measuring human mutation frequencies, (ii) associating genetic variation with disease, (iii) analyzing genomic instability in relation to cancer and aging, and (iv) linkage analysis and mapping of disease genes.The possibility to identify DNA sequence heterogeneity is of major importance for the analysis of genetic diseases and genomic instabilities. This identification depends on the availability of probes that detect variable sites in the genome and on the resolution of electrophoretic separation techniques for the analysis of DNA restriction fragments.The discovery of hyperpolymorphic VNTR (variable number of tandem repeat) DNA sequences or minisatellites has greatly facilitated studies of genetic variation in the human population (1-6). It has been demonstrated that so-called core probes derived from minisatellites can be used to simultaneously detect a large number of hyperpolymorphic VNTR loci, dispersed in the genome, to provide genetic fingerprints of human individuals (7,8 Electrophoretic Separations. Agarose gel electrophoresis of 5 ,ug of DNA restriction fragments was performed in a horizontal 1.2% gel in lx TAE (40 mM Tris'HCl, pH 7.4/20 mM sodium acetate/1 mM NaEDTA) at 65 V for 14-30 hr.Gels were stained for 10 min in a solution containing ethidium bromide (EtdBr) at 0.1 ug/ml followed by destaining for at least 30 min. Two-dimensional separations of 5 ,ug of DNA restriction fragments were performed in 1-mm-thick polyacrylamide gels (acrylamide/bisacrylamide, 37:1) using a gel apparatus that was essentially the same as the one described by Fischer and Lerman (12). The first dimension was run in a neutral 6% gel at 50'C for 2 hr at 250 V in lx TAE. The separation patterns were visualized by staining the gel in the dark with EtdBr (0.1 ,ug/ml) for 10 min, followed by destaining for at least 30 min. The 0.34-to 2.8-kbp region (probe 33.15) or the 0.54-to 10-kbp region ...

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“…DNA was packaged in vitro using Gigapack Plus [Stratagene Cloning Systems, La Jolla, CA] and plated onto E. coli strain LE392. The resulting library (36,500 recombinant phage) was screened by in situ plaque hybridization using VTR4.1 (7). The EcoRI-BglII fragment of one positive phage, 1.1, containing VTR.…”

Section: Vtr11 Cloning and Sequencingmentioning

confidence: 99%

“…DNA sequence comparisons were performed using the Microgenie sequence analysis program [Beckman, Inc, Palo Alto, CA] and the Genetic Sequence Data Bank (GenBank). Southern blots were performed as previously described (7). Mi1 2 3 4 t .…”

Section: Vtr11 Cloning and Sequencingmentioning

confidence: 99%

The human minisatellite consensus at breakpoints of oncogene translocations

1990

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A reexamination of human minisatellite (hypervariable) regions following the cloning and sequencing of the new minisatellite, VTR1.1, revealed that many of these structures possessed a strongly conserved copy of the chi-like octamer, GC[A/T]GG[A/T]GG. In oncogene translocations apparently created by aberrant VDJ recombinase activity, this VTR octamer was often found within a few bases of the breakpoint (p less than 10(-10)). Three bcl2 rearrangements which occurred within 2 bp of one another were located precisely adjacent to this consensus; it defined the 5' border of that oncogene's major breakpoint cluster. Several c-myc translocations also occurred within 2 bp of this sequence. While the appearance of a chi-like element in polymorphic minisatellite sequences is consistent with a role promoting either recombination or replication slippage, the existence of such elements at sites of somatic translocations suggests chi function in site-specific recombination, perhaps as a subsidiary recognition signal in immunoglobulin gene rearrangement. We discuss the implications of these observations for mechanisms by which oncogene translocations and minisatellite sequences are generated.

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A variable tandem repeat locus mapped to chromosome band 10q26 is amplified and rearranged in leukocyte DNAs of two cancer patients

Cited by 15 publications

References 15 publications

A family of short, interspersed repeats is associated with tandemly repetitive DNA in the human genome.

A family of short, interspersed repeats is associated with tandemly repetitive DNA in the human genome.

Two-dimensional DNA fingerprinting of human individuals.

The human minisatellite consensus at breakpoints of oncogene translocations

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