Tightly clustered 11q23 and 22q11 breakpoints permit PCR-based detection of the recurrent constitutional t(11;22) - PubMed (original) (raw)

Tightly clustered 11q23 and 22q11 breakpoints permit PCR-based detection of the recurrent constitutional t(11;22)

H Kurahashi et al. Am J Hum Genet. 2000 Sep.

Abstract

Palindromic AT-rich repeats (PATRRs) on chromosomes 11q23 and 22q11 at the constitutional t(11;22) breakpoint are predicted to induce genomic instability, which mediates the translocation. A PCR-based translocation-detection system for the t(11;22) has been developed with PCR primers flanking the PATRRs of both chromosomes, to examine the involvement of the PATRRs in the recurrent rearrangement. Forty unrelated carriers of the t(11;22) balanced translocation, plus two additional, independent cases with the supernumerary-der(22) syndrome, were analyzed to compare their translocation breakpoints. Similar translocation-specific junction fragments were obtained from both derivative chromosomes in all 40 carriers of the t(11;22) balanced translocation and from the der(22) in both of the offspring with unbalanced supernumerary-der(22) syndrome, suggesting that the breakpoints in all cases localize within these PATRRs and that the translocation is generated by a similar mechanism. This PCR strategy provides a convenient technique for rapid diagnosis of the translocation, indicating its utility for prenatal and preimplantation diagnosis in families including carriers of the balanced translocation.

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Figures

Figure 1

Figure 1

PCR primers used in analysis of the t(11;22) breakpoint. The white portion of the sequences denotes the PATRR, which includes the breakpoint region; gray portions denote chromosome 11; and hatched portions denote chromosome 22. PCR primers are indicated, with their orientation shown by arrows.

Figure 2

Figure 2

PCR results from one t(11;22) family. a, Pedigree of t(11;22) family. The blackened circle denotes the proband, who has the supernumerary-der(22) syndrome, and the circle with a black dot denotes the mother who is a carrier of the balanced translocation. b, PCR analysis for der(11). c, PCR analysis for der(22). Lanes M show 1-kb plus DNA ladder (GIBCO BRL); lanes P show results for the carrier of the t(11;22) balanced translocation (case 1), who serves as a positive control; the numbered lanes show results for DNA from individuals with the corresponding ID number in the pedigree Size markers (in bp) are indicated. The largest band is the authentic PCR product (arrows). The ladder is an artifact that originates from “stutter bands,” on amplification of the AT-rich repeat.

References

Electronic-Database Information

    1. Unbalanced 11/22 Translocation, http://www.nt.net/~a815/index.html

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