Microsatellite Polymorphism Linkage Map of Human Chromosome 13q

Bowcock, Anne M.; Osborne-Lawrence, Sherri; Barnes, R. Bowling; Chakravarti, Aravinda; Washington, Sarah S.; Dunn, Courtney M.

doi:10.1006/geno.1993.1071

Cited by 49 publications

(23 citation statements)

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“…To identify tumors with LOH of the region containing BRCA2, tumors and matched blood specimens were genotyped for polymorphic`CA' dinucleotide repeat markers at D13S260 and D13S267 as described elsewhere (Bowcock et al, 1993). Oligonucleotide primer sequences were obtained from the Genome Data Base.…”

Section: Loss Of Heterozygositymentioning

confidence: 99%

Infrequency of BRCA2 alterations in head and neck squamous cell carcinoma

et al. 1997

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Alterations of BRCA2 result in increased susceptibility to breast cancer in both men and women (relative lifetime risks of 0.06 and 0.8 respectively). BRCA2 maps to 13q12-q13 and encodes a transcript of 10 157 bp. Other cancers that have been described in BRCA2 mutation carriers include those of the larynx. Human chromosome 13q has been shown previously by LOH studies to harbor several tumor suppressor genes for head and neck squamous cell carcinoma (HNSCCs). We therefore examined the role of BRCA2 in the development of these cancers. Only 6/22 (27%) of the laryngeal cancers we examined demonstrated LOH of the BRCA2-containing region. These and 10 other HNSCCs of dierent origins that were demonstrated by LOH studies to have lost the region of chromosome 13 containing BRCA2 were examined for alterations in this gene. SSCP analysis failed to reveal any alterations leading us to conclude that BRCA2 alterations are not frequently involved in the pathogenesis of HNSCCs and that the observed LOH of chromosome 13 loci is due to other, as yet, unidenti®ed tumor suppressor gene(s). Interestingly tumors with LOH in this region (proximal to D13S118) were far more likely to be derived from women than men. This is unusual since HNSCCs are usually fourfold more common in men than in women.

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Section: Loss Of Heterozygositymentioning

confidence: 99%

Infrequency of BRCA2 alterations in head and neck squamous cell carcinoma

et al. 1997

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“…The high similarity in allele sizes at each locus inspired the hypothesis that stepwise mutation mechanisms through replication slippage might be involved (1)(2)(3)(4). The direct knowledge of spontaneous mutation and the estimation of mutation rates in microsatellites are largely due to the contribution of large scale pedigree studies in the search for disease genes (5)(6)(7)(8)(9). Such studies have shown that more than 90% of mutations result in the expansion or contraction of the alleles by a single repeat unit (2 to 4 bp).…”

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Mutation rate varies among alleles at a microsatellite locus: Phylogenetic evidence

Macaubas

Hallmayer

et al. 1996

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

141

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The understanding of the mutational mechanism that generates high levels of variation at microsatellite loci lags far behind the application of these genetic markers. A phylogenetic approach was developed to study the pattern and rate of mutations at a dinucleotide microsatellite locus tightly linked to HLA-DQB1 (DQCAR). A random Japanese population (n ‫؍‬ 129) and a collection of multiethnic samples (n ‫؍‬ 941) were typed at the DQB1 and DQCAR loci. The phylogeny of DQB1 alleles was then reconstructed and DQ-CAR alleles were superimposed onto the phylogeny. This approach allowed us to group DQCAR alleles that share a common ancestor. The results indicated that the DQCAR mutation rate varies drastically among alleles within this single microsatellite locus. Some DQCAR alleles never mutated during a long period of evolutionary time. Sequencing of representative DQCAR alleles showed that these alleles lost their ability to mutate because of nucleotide substitutions that shorten the length of uninterrupted CA repeat arrays; in contrast, all mutating alleles had relatively longer perfect CA repeat sequences.Microsatellites, which are abundant in the human genome, are highly polymorphic due to allelic variation in the number of repeat units of 2-5 base pairs. These genetic markers are widely used in human genetics, although an understanding of the mutational mechanism that generates such a high level of variation lags far behind their applications. The high similarity in allele sizes at each locus inspired the hypothesis that stepwise mutation mechanisms through replication slippage might be involved (1-4). The direct knowledge of spontaneous mutation and the estimation of mutation rates in microsatellites are largely due to the contribution of large scale pedigree studies in the search for disease genes (5-9). Such studies have shown that more than 90% of mutations result in the expansion or contraction of the alleles by a single repeat unit (2 to 4 bp). These studies also estimated that the mutation rates of microsatellites studied range from 1.2 ϫ 10 Ϫ4 to 1.5 ϫ 10 Ϫ2 . Comparison of allele sequences revealed very complex mutation patterns (10-12). However, the laborious pedigree studies prevent one from observing enough mutations for each locus and consequently all the conclusions drawn are based on a large collection of loci.Population genetic studies of microsatellite loci have been fruitful in revealing possible pattern of mutations. It has been shown that a simple stepwise mutation model (SMM; ref. 13), which is intuitively compatible with replication slippage mechanism, can describe the behaviors of many microsatellite loci in the populations (14-16). An extended SMM that allows a few big changes in repeat number (multistep SMM) may be more suitable for microsatellites (16,17). However, since only simple summary statistics were used in the above studies, characterization of individual locus was not possible. Furthermore, the pattern and rate of mutations at microsatellites may vary among loci (14, 18...

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“…The markers D13S162 and D13S160 flanking the CLN5 critical region had been assigned earlier by genetic means (Dib et al 1992;Bowcock et al 1993;Buetow et al 1994), by radiation hybrid mapping (Shaw et al 1995), and by somatic cell hybrids (Hawthorn and Cowell 1995) to the region ranging from 13q21 to 13q32. The accurate chromosomal localization of this genomic region had to be verified and possibly refined.…”

Section: Refined Chromosomal Localization Of the Cln5 Critical Regionmentioning

confidence: 99%

Utilization of FISH in positional cloning: an example on 13q22.

Laan¹,

Isosomppi²,

Klockars³

et al. 1996

Genome Res.

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in positional cloning the initial assignment of a gene to a specific chromosomal locus is followed by physical mapping of the critical region. The construction of a high-resolution physical map still involves considerable effort. However, new high-resolution fluorescence in situ hybridization (FISH) techniques have facilitated this process substantially. Here we summarize a strategy that combines a spectrum of FISH techniques [metaphase, interphase, mechanically stretched chromosomes (MSCs), and fiber-FISH on free chromatin] for the construction and characterization of a high-resolution physical map for a positional cloning project. The chromosomal region 13q22, containing the locus of the variant form of the neuronal ceroid lipofuscinosis (vLINCL, CLNS) disease, serves here as an example for this process. We used metaphase FISH to exclude positionally a candidate gene, to refine the locus to 13q22, and to analyze the possible chimerism of the YACs in the region. Both metaphase and interphase FISH techniques were applied to determine the low-resolution distances between the restricting markers. FISH using MSCs confirmed the centromeric-telomeric order of the clones and facilitated the estimation of the size of the gaps between the clones. Finally, fiber-FISH was found to be the method of choice for the construction of an accurate high-resolution map of the contig established over the restricted region. Thus, FISH techniques in combination with genetic mapping data enabled the refinement of the initial 4-cM region to a high-resolution map of only 400 kb in length. Here the FISH strategy replaced the need for many laborious traditional physical mapping methods, e.g., pulsed-field gel electrophoresis.

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Microsatellite Polymorphism Linkage Map of Human Chromosome 13q

Cited by 49 publications

References 0 publications

Infrequency of BRCA2 alterations in head and neck squamous cell carcinoma

Infrequency of BRCA2 alterations in head and neck squamous cell carcinoma

Mutation rate varies among alleles at a microsatellite locus: Phylogenetic evidence

Utilization of FISH in positional cloning: an example on 13q22.

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