Human restriction fragment length polymorphisms and cancer risk assessment

Krontiris, Theodore G.; DiMartino, Nancy A.; Colb, Mark; Mitcheson, H. David; Parkinson, David

doi:10.1002/jcb.240300405

Cited by 42 publications

(31 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Krontiris' studies showed a similar incidence in controls to our own, i.e., 3.9% (Krontiris et al, 1985) and 3.4% (Krontiris et al, 1986), but a highly significant increase (P<0.01 and P<0.001 respectively) in the cancer patients, which was not diminished when the solid tumour sub group was considered separately. (The majority of cases were leukaemias.)…”

Section: Discussionsupporting

confidence: 78%

See 1 more Smart Citation

Ha-ras restriction fragment length polymorphisms in colorectal cancer

Wyllie

Wynford-Thomas²,

Lemoine³

et al. 1988

Br J Cancer

View full text Add to dashboard Cite

Summary The possibility of an association between restriction fragment length polymorphisms (RFLPs) at the Ha-ras gene locus and susceptibility to develop colorectal cancer has been investigated. Leucocyte DNA from 46 carcinoma patients and 49 controls was analysed by Southern blotting to determine the size distribution of restriction fragments containing the variable tandem repeat 3' to the Ha-ras gene. Four predominant allelic fragments were found in both groups (in AvalI digests having sizes of 1.55, 2.0, 2.65 and 3.15 kilobases [kb]), together with a variety of 'rare' alleles (with individual frequencies <5%). The overall prevalence of rare alleles was not significantly different between cancer and control groups. The distribution of the common alleles, however, differed significantly. The combined frequency of the two larger alleles (a3 and a4) was approximately twice as high in the cancer group (34%) as in controls (18%) (P<0.025), which was reflected in a highly significant increase in the proportion of individuals carrying an a3 or a4 allele.

show abstract

Section: Discussionsupporting

confidence: 78%

“…Since the risk of malignancy may be cell-type specific the observed effect in this and a later series of mixed cancers (Krontiris et al, 1986) may have been seriously 'diluted'. We and others (Thein et al, 1986;Heighway et al, 1986;Gerhard et al, 1987) have therefore carried out a similar analysis of patients with a single tumour category.…”

mentioning

confidence: 80%

Ha-ras restriction fragment length polymorphisms in colorectal cancer

Wyllie

Wynford-Thomas²,

Lemoine³

et al. 1988

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…2002). We replaced the Saccharomyces cerevisiae HIS4 considered common if they occur in Ͼ7% of the populapromoter region with the a1 common allele of the HRAS1 tion (Krontiris et al 1986). The common alleles differ minisatellite from humans and demonstrated that this from one another in the arrangement of the repeat types model system recapitulated in yeast all of the phenowithin each tract and the number of repeats in the tract.…”

Section: Inisatellites Are Tracts Of Tandemly Repeatedmentioning

confidence: 99%

Length and Sequence Heterozygosity Differentially Affect HRAS1 Minisatellite Stability During Meiosis in Yeast

Jauert

Kirkpatrick

2005

Genetics

View full text Add to dashboard Cite

Minisatellites, one of the major classes of repetitive DNA sequences in eukaryotic genomes, are stable in somatic cells but destabilize during meiosis. We previously established a yeast model system by inserting the human Ha-ras/HRAS1 minisatellite into the HIS4 promoter and demonstrated that our system recapitulates all of the phenotypes associated with the human minisatellite. Here we demonstrate that meiotic minisatellite tract-length changes are half as frequent in diploid cells harboring heterozygous HRAS1 minisatellite tracts in which the two tracts differ by only two bases when compared to a strain with homozygous minisatellite tracts. Further, this decrease in alteration frequency is entirely dependent on DNA mismatch repair. In contrast, in a diploid strain containing heterozygous minisatellite tract alleles differing in length by three complete repeats, length alterations are observed at twice the frequency seen in a strain with homozygous tracts. Alterations consist of previously undetectable gene conversion events, plus nonparental length alteration events seen previously in strains with homozygous tracts. A strain containing tracts with both base and length heterozygosity exhibits the same level of alteration as a strain containing only length heterozygosity, indicating that base heterozygosity-dependent tract stabilization does not affect tract-length alterations occurring by gene conversion. M INISATELLITES are tracts of tandemly repeatedand MS32, for example) exhibit very high rates of tractlength alterations; these types are often utilized for fo-DNA in which the repeat unit ranges in length rensic DNA fingerprinting. Alterations in minisatellite from 10 to 100 nucleotides. In addition, within a given tracts are often polar in nature (Armour et al. 1993; tract, variations on the canonical repeat sequence can Jeffreys et al. 1994), occurring at one side of the tract occur. For example, the human HRAS1 minisatellite tract preferentially. This polarity, and the meiotic timing of is commonly composed of tandem iterations of four varithe alterations, has led to the hypothesis that alterations ants of a 28-bp sequence: 5Ј-ACACTCGCCCTTCTCTC in minisatellite sequences result from a recombination CAGGGGACGCC-3Ј. Repeats contain either a C or a G event at the locus rather than during replication. at the seventh and/or fifteenth nucleotide (as indicated Identification of the meiotic factors underlying miniby underlining) (Capon et al. 1983). Additionally, in satellite stability has been complicated by the high level the human population there are four different common of variability exhibited by minisatellite sequences in the alleles of the minisatellite, designated a1-a4 (Krontiris human population. We developed the yeast HIS4-HRAS1 et al. 1985), which consist of a particular combination model system to overcome these difficulties (Jauert et of the four repeat types in a defined order. Alleles are al. 2002). We replaced the Saccharomyces cerevisiae HIS4 considered common if they occur in Ͼ7% of...

show abstract

“…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).…”

mentioning

confidence: 99%

“…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.…”

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.

View full text Add to dashboard Cite

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...

show abstract

Human restriction fragment length polymorphisms and cancer risk assessment

Cited by 42 publications

References 18 publications

Ha-ras restriction fragment length polymorphisms in colorectal cancer

Ha-ras restriction fragment length polymorphisms in colorectal cancer

Length and Sequence Heterozygosity Differentially Affect HRAS1 Minisatellite Stability During Meiosis in Yeast

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

Contact Info

Product

Resources

About