Routinely distinguishing normal and balanced translocation carrier embryos using snp arrays


      Many translocation carrier couples convey a strong interest in preventing transmission to their offspring, sparing them the reproductive challenges they faced. However, contemporary methods of comprehensive chromosome screening (CCS) cannot reliably distinguish between normal embryos and those that carry a balanced translocation. This study was conducted to develop a method that can concurrently identify unbalanced and aneuploid embryos, and, for the first time, distinguish translocation carrier and truly normal embryos all from the same embryonic trophectoderm biopsy SNP array data.


      Blinded evaluation of balanced/normal embryos from a translocation carrier patient.

      Materials and Methods

      262K SNP arrays were used on a family trio (parents and child) to phase the parental reciprocal translocation carrier. Informative SNPs 5 megabases (Mb) on each side of the chromosome breakpoints (heterozygous in the carrier and homozygous in the normal parent) were used to predict whether otherwise euploid embryos inherited the translocated chromosome and thus would be obligate balanced translocation carriers. Outcomes were evaluated against known genetic status from separate PCR analysis of a specific microdeletion (known to be associated with the translocation) in order to confirm results.


      A total of 67 embryos were evaluated from a couple carrying 46,XX,t(2:20)(q21;p12.2); 12 were euploid and balanced or normal for the translocation based on conventional copy number analysis. 128 (chr2) and 191 (chr20) informative SNPs were identified within 5 Mb of the breakpoints. A child born without the translocation was used to phase the maternal chromosomes for the informative SNPs. When these SNPs were evaluated in blinded embryos, 2 were identified as carriers, and 10 as normal, which was 100% consistent with the known status of each embryo.


      We have developed a proof of principle that phased informative SNPs can be evaluated to routinely distinguish balanced carrier and normal embryos in parallel with conventional CCS using SNP array technology. An ongoing clinical trial will continue to accumulate evidence of the predictive value for clinical outcomes and general applicability in additional cases. This may provide couples with a balanced translocation an additional selection criterion when considering which embryo to transfer.