Fine mapping of the constitutional translocation t(11;22)(q23;q11) (original) (raw)

Abstract.

Translocation t(11;22)(q23;q11) is the most common constitutional reciprocal translocation in man. Balanced carriers are phenotypically normal, except for decreased fertility, an increased spontaneous abortion rate and a possible predisposition to breast cancer in some families. Here, we report the high resolution mapping of the t(11;22)(q23;q11) breakpoint. We have localised the breakpoint, by using fluorescence in situ hybidisation (FISH) walking, to a region between D11S1340 and WI-8564 on chromosome 11, and D22S134 and D22S264 on chromosome 22. We report the isolation of a bacterial artificial chromosome (BAC) clone spanning the breakpoint in 11q23. We have narrowed down the breakpoint to an 80-kb sequenced region on chromosome 11 and FISH analysis has revealed a variation of the breakpoint position between patients. In 22q11, we have sequenced two BACs (BAC2280L11 and BAC41C4) apparently mapping to the region; these contain low copy repeats (LCRs). Southern blot analysis with probes from BAC2280L11 has revealed different patterns between normal controls and translocation carriers, indicating that sequences similar/identical to these probes flank the translocation breakpoint. The occurrence of LCRs has previously been associated with genomic instability and "unclonable" regions. Hence, the presence of such repeats renders standard translocation breakpoint cloning techniques ineffective. Thus, we have used high resolution fiber-FISH to study this region in normal and translocation cases by using probes from 22q11, LCRs and 11q23. We demonstrate that the LCR containing the gap in 22q11 is probably substantially larger than the previous estimates of 100 kb. Using fiber-FISH, we have localised the breakpoint in 22q11 to approximately 20–40 kb from the centromeric border of the LCR (i.e. the telomeric end of AC006547) and have confirmed the breakpoint position on 11q23.

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Authors and Affiliations

1. Department of Molecular Medicine, Clinical Genetics Unit, CMM building L8, Karolinska Hospital, S-171 76 Stockholm, Sweden, Sweden
   Isabel Tapia-Páez, Kevin P. O'Brien, Sigrid Sahlén, Darek Kedra, Carl E. G. Bruder, Elisabeth Blennow & Jan P. Dumanski
2. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital, SE-751 85 Uppsala, Sweden, Sweden
   Björn Andersson
3. Microbiology and Tumor Biology Center (MTC), Karolinska Institutet, S-171 77, Stockholm, Sweden, Sweden
   Maria Kost-Alimova & Stephan Imreh
4. Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA, USA
   Bruce A. Roe & Ping Hu

Authors

1. Isabel Tapia-Páez
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2. Kevin P. O'Brien
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3. Maria Kost-Alimova
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4. Sigrid Sahlén
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5. Darek Kedra
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6. Carl E. G. Bruder
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7. Björn Andersson
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8. Bruce A. Roe
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9. Ping Hu
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10. Stephan Imreh
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11. Elisabeth Blennow
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12. Jan P. Dumanski
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Tapia-Páez, I., O'Brien, K., Kost-Alimova, M. et al. Fine mapping of the constitutional translocation t(11;22)(q23;q11).Hum Genet 106, 506–516 (2000). https://doi.org/10.1007/s004390000287

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• Received: 09 November 1999
• Accepted: 07 March 2000
• Published: 20 April 2000
• Issue Date: May 2000
• DOI: https://doi.org/10.1007/s004390000287

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