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Large scale whole genome and exome sequencing is uncovering a plethora of novel mutations that cause highly penetrant, early-onset, severe, or later-onset life-threatening dominant and recessive disorders. For couples who are known carriers of mutant alleles, preimplantation genetic diagnosis enables the detection of genetic disorders in embryos that have been fertilized in vitro, thereby avoiding their transmission to offspring. Traditional PGD methods require a mutation and family specific work-up.
We and others have developed generic methods that can be readily applied for all transmitted genetic disorders. They are termed karyomapping and haplarithmisis. The methods reconstructs genome-wide haplotype architectures as well as the copy-number and segregational origin of those haplotypes byemploying phased parental genotypes and deciphering WGA-distorted SNP B-allele fractions. I will present the principles, the use and the results of its implementation since clinical implementation. The introduction of genome wide screening of embryo's raised novel ethical questions. The principles guiding embryo selection and prioritization that are applied at our center according to the chromosomal content and mutational load of the embryos, will be presented. I will present novel technical developments broadening the scope of use. In addition, I will present new insights in the origins and mechanisms leading to early meiotic and mitotic errors as well as on the origin of mixoploid and chimaeric embryos.
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© 2019 Published by Elsevier Inc.