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Mapping of balanced chromosome translocation breakpoints to the basepair level from microdissected chromosomes.

Obenauf AC, Schwarzbraun T, Auer M, Hoffmann EM, Waldispuehl-Geigl J, Ulz P, Günther B, Duba HC, Speicher MR, Geigl JB - J. Cell. Mol. Med. (2010)

Bottom Line: The analysis of structural variants associated with specific phenotypic features is promising for the elucidation of the function of involved genes.There is, however, at present no approach allowing the rapid mapping of chromosomal translocation breakpoints to the basepair level from a single chromosome.The amplification products of the der(7) and of the der(13) were hybridized to custom-made arrays, enabling us to define primers at flanking breakpoint regions and thus to fine-map the breakpoints to the basepair level.

View Article: PubMed Central - PubMed

Affiliation: Institute of Human Genetics, Medical University of Graz, Graz, Austria.

ABSTRACT
The analysis of structural variants associated with specific phenotypic features is promising for the elucidation of the function of involved genes. There is, however, at present no approach allowing the rapid mapping of chromosomal translocation breakpoints to the basepair level from a single chromosome. Here we demonstrate that we have advanced both the microdissection and the subsequent unbiased amplification to an extent that breakpoint mapping to the basepair level has become possible. As a case in point we analysed the two breakpoints of a t(7;13) translocation observed in a patient with split hand/foot malformation (SHFM1). The amplification products of the der(7) and of the der(13) were hybridized to custom-made arrays, enabling us to define primers at flanking breakpoint regions and thus to fine-map the breakpoints to the basepair level. Consequently, our results will also contribute to a further delineation of causative mechanisms underlying SHFM1 which are currently unknown.

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Exact localization of the chromosome 7 breakpoint between genes SHFM1 and DLX6. The red frame indicates the critical region of the SHFM1-syndrome based on cases with deletions, inversions and breakpoints. Pink bars indicate patients with deletions, violet bars indicate inversions and blue bars translocation regions which were not mapped to the basepair level. Patient data were retrieved from the Decipher database (https://decipher.sanger.ac.uk), the data in this image are based on the Ensembl Genome Browser, Release 57, hg19).
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fig04: Exact localization of the chromosome 7 breakpoint between genes SHFM1 and DLX6. The red frame indicates the critical region of the SHFM1-syndrome based on cases with deletions, inversions and breakpoints. Pink bars indicate patients with deletions, violet bars indicate inversions and blue bars translocation regions which were not mapped to the basepair level. Patient data were retrieved from the Decipher database (https://decipher.sanger.ac.uk), the data in this image are based on the Ensembl Genome Browser, Release 57, hg19).

Mentions: This information was sufficient for the design of flanking primer pairs, which we used in a final step to sequence the breakpoints. The exact location of the breakpoints is [hg 19] on chromosome 7 at position 96466302 (chromosome band 7q21.3) and on chromosome 13 at position 98184040 (chromosome band 13q32.1). There was no gene or transcriptional active region close to the chromosome 13 breakpoint (Fig. S2). The chromosome 7 breakpoint is located between genes SHFM1 and DLX6 and did not disrupt any presently known transcriptional active region (Fig. 4).


Mapping of balanced chromosome translocation breakpoints to the basepair level from microdissected chromosomes.

Obenauf AC, Schwarzbraun T, Auer M, Hoffmann EM, Waldispuehl-Geigl J, Ulz P, Günther B, Duba HC, Speicher MR, Geigl JB - J. Cell. Mol. Med. (2010)

Exact localization of the chromosome 7 breakpoint between genes SHFM1 and DLX6. The red frame indicates the critical region of the SHFM1-syndrome based on cases with deletions, inversions and breakpoints. Pink bars indicate patients with deletions, violet bars indicate inversions and blue bars translocation regions which were not mapped to the basepair level. Patient data were retrieved from the Decipher database (https://decipher.sanger.ac.uk), the data in this image are based on the Ensembl Genome Browser, Release 57, hg19).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822999&req=5

fig04: Exact localization of the chromosome 7 breakpoint between genes SHFM1 and DLX6. The red frame indicates the critical region of the SHFM1-syndrome based on cases with deletions, inversions and breakpoints. Pink bars indicate patients with deletions, violet bars indicate inversions and blue bars translocation regions which were not mapped to the basepair level. Patient data were retrieved from the Decipher database (https://decipher.sanger.ac.uk), the data in this image are based on the Ensembl Genome Browser, Release 57, hg19).
Mentions: This information was sufficient for the design of flanking primer pairs, which we used in a final step to sequence the breakpoints. The exact location of the breakpoints is [hg 19] on chromosome 7 at position 96466302 (chromosome band 7q21.3) and on chromosome 13 at position 98184040 (chromosome band 13q32.1). There was no gene or transcriptional active region close to the chromosome 13 breakpoint (Fig. S2). The chromosome 7 breakpoint is located between genes SHFM1 and DLX6 and did not disrupt any presently known transcriptional active region (Fig. 4).

Bottom Line: The analysis of structural variants associated with specific phenotypic features is promising for the elucidation of the function of involved genes.There is, however, at present no approach allowing the rapid mapping of chromosomal translocation breakpoints to the basepair level from a single chromosome.The amplification products of the der(7) and of the der(13) were hybridized to custom-made arrays, enabling us to define primers at flanking breakpoint regions and thus to fine-map the breakpoints to the basepair level.

View Article: PubMed Central - PubMed

Affiliation: Institute of Human Genetics, Medical University of Graz, Graz, Austria.

ABSTRACT
The analysis of structural variants associated with specific phenotypic features is promising for the elucidation of the function of involved genes. There is, however, at present no approach allowing the rapid mapping of chromosomal translocation breakpoints to the basepair level from a single chromosome. Here we demonstrate that we have advanced both the microdissection and the subsequent unbiased amplification to an extent that breakpoint mapping to the basepair level has become possible. As a case in point we analysed the two breakpoints of a t(7;13) translocation observed in a patient with split hand/foot malformation (SHFM1). The amplification products of the der(7) and of the der(13) were hybridized to custom-made arrays, enabling us to define primers at flanking breakpoint regions and thus to fine-map the breakpoints to the basepair level. Consequently, our results will also contribute to a further delineation of causative mechanisms underlying SHFM1 which are currently unknown.

Show MeSH
Related in: MedlinePlus