Routine detection of consanguinity through preimplantation genetic testing in human embryos.
Catherine Kratka, Jia Xu, Jennifer Eccles, Diego Marin, Nathan Treff
Author Information
Catherine Kratka: Genomic Prediction Inc., North Brunswick Township, New Jersey, USA.
Jia Xu: Genomic Prediction Inc., North Brunswick Township, New Jersey, USA.
Jennifer Eccles: Genomic Prediction Inc., North Brunswick Township, New Jersey, USA.
Diego Marin: Genomic Prediction Inc., North Brunswick Township, New Jersey, USA.. Electronic address: diego@genomicprediction.com.
Nathan Treff: Genomic Prediction Inc., North Brunswick Township, New Jersey, USA.; Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers University, New Brunswick, New Jersey, USA.
RESEARCH QUESTION: Can a single-nucleotide polymorphism array-based preimplantation genetic testing (PGT) platform routinely detect consanguinity in preimplantation embryos? DESIGN: A validation set consisting of 29 clinical PGT cases (five cases with confirmed consanguinity [positive control cases] and 24 randomly selected non-consanguineous cases [negative control cases]) was used to define a genetic threshold for the routine detection of consanguinity. PLINK software was used to identify all regions of homozygosity (ROH) greater than 5 Mb on each autosome. The percentage of ROH was then calculated and compared between the positive and negative control cases to determine a threshold. Next, the threshold was used to create a specific criterion that was applied to 6,380 clinical PGT cases (27,378 embryos in total) to calculate the prevalence of consanguineous cases within a single PGT laboratory. RESULTS: The selected criterion defined cases as consanguineous when they contained two or more embryos with ROH percentages of 0.5% or more. Positive and negative control cases from the validation set fulfilled and failed this criterion, respectively. Of the 6380 cases evaluated, 0.45% (29) were defined as consanguineous. CONCLUSIONS: This study describes a PGT platform that can routinely screen for parental consanguinity by evaluating regions of homozygosity in IVF-derived embryos during routine genetic testing. Consanguinity can be detected without prior knowledge of a parental relationship. This can help to improve the utility of PGT and identify embryos at increased risk of recessive disease associated with consanguinity.
