Optimization of PGD for recurrent t(11;22) carrier

Introduction t(11;22)(q23;q11) is the most common reciprocal translocation in humans. Carriers of the balanced t(11;22) are phenotypically normal, but they often manifest problems with reproduction such as infertility, recurrent pregnancy loss, or the birth of unbalanced offspring with the Emanuel syndrome. Preimplantation genetic diagnosis (PGD) is the one of the solution for such reproductive problems. In general, comprehensive chromosomal analyses by microarray-based comparative genomic hybridization (aCGH) or next generation sequence (NGS) are applied for PGD. In addition, since the breakpoints of both chromosomes 11 and 22 are localized within a small region, translocation-specific PCR might be applied to the PGD for t(11;22). Material and Methods To set up optimal PGD method for t(11;22), we compared various cytogenetics analyses using whole genome amplified DNA from lymphoblastoid cell line from a patient with Emanuel syndrome having trisomy at the regions distal to 11q23 and proximal to 22q11. Results NGS is suited for determination of the copy number of the unbalanced translocation region better than aCGH or SNP array analyses. CNV-seq method improves detection sensitivity further. However, since the chromosome 22 breakpoint region includes a considerable number of segmental duplications, all methods have low sensitivity to detect copy number change at the proximal 22q11 region. Since translocation-specific PCR can detect the translocation chromosomes in whole genome amplified DNA, combination of NGS and this PCR system is useful to predict the segregation pattern of translocated chromosomes. Conclusions Translocation-specific PCR is a simple, rapid and cost-effective method in the PGD for tt(11;22) ranslocation.