Patient-specific probes for preimplantation genetic diagnosis of structural and numerical aberrations in interphase cells

Purpose: Our purpose was to evaluate the utility of translocation breakpoint-spanning DNA probes for prenatal genetic diagnosis of structural and numerical chromosome aberrations in interphase cells. Methods: Breakpoint-spanning translocation probes were isolated from large insert DNA libraries and labeled so that the breakpoint regions were stained in different colors. Hybridization conditions were optimized using blastomeres biopsied from donated embryos. Probes were then applied to analyze patient blastomeres. Results: We prepared translocation breakpoint-specific probes for 18 in vitro fertilization patients. Here. we describe the preparation of probes for two patients carrying balanced translocations involving chromosome 11 [t(11;22)(q23;q11), t(6;11)(p22.1;p15.3)]. The breakpoint cloning procedure could be accomplished in about 3-5 weeks. Additional time was needed to optimize probes. Application of probes demonstrated numerical as well as structural abnormalities. Conclusions: Breakpoint-spanning probes allow chromosome analysis in interphase cells as required for preimplantation genetic diagnosis screening of blastomeres.