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Tuesday, July 10 • 11:34 - 12:46
Session 4 | The expanding scope of Non-invasive prenatal testing Invited Presentation: 4-2 Haplotyping and copy number profiling of single cells by using extended family members: broadening the applicability of PGD

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Haplotyping and copy number profiling of single cells by using extended family members: broadening the applicability of PGD
Jia Ding1, Aspasia Destouni2, Joris Vermeesch3

1UZ Leuven, Leuven, Belgium
2KUL, Leuven, Belgium
3Center for Medical genetics, Katholieke Universiteit Leuven, Leuven, Belgium
Genome-wide linkage-analysis by haplotyping the entire genome of preimplantation embryos is being implemented as a generic approach for genetic diagnosis of inherited mutations. To enable the phasing of the genotypes into haplotypes, genotyping direct family members of the prospective parent carrying the mutation is required. Currently, the algorithm uses either (1) both parents of the affected prospective parent or (2) an affected or unaffected child of the affected couple. However, in many cases DNA from offspring and grandparents might not be available to phase the parental genotypes. This limitation deprives couples of gaining access to the generic genome-wide haplotyping-based PGD.
To expand the dynamic range of the technology in clinical practice, we optimized the algorithmic workflow to phase the parental genotypes using parental siblings. Our method exploits allelic states between family members and is independent of pedigree structure. As the genetic mutation is embedded in a local haplotype, it is possible to deduce the affected haplotype and copy number profiling of the embryo.
Retrospective phasing of the parental haplotypes in twelve concluded PGD cases involving the analysis of 67 embryos in the Centre for Human Genetics, UZ Leuven between 2015-2016. We compared the genome-wide haplotypes and copy number states of each embryo, which were obtained with the new phasing approach to those initially obtained with the validated phasing strategy using grandparents and offspring during clinical PGD. In accordance to the expected degree of genetic relatedness between full siblings, new phasing approach could establish a diagnostic result in six out of the twelve (50%) of PGD couples included in this study.
We developed a method to enable generic haplotyping and genome-wide copy number profiling without the need to genotype grandparents or affected/unaffected offspring. This service significantly reduces the emotional stress imposed to the couple higher costs and increased waiting times in case a “private” protocol has to be set-up. More families can benefit from this new option without the need for customized test development. By including more than one extended family member, the chance of diagnosis the embryo will get increased. A rapid Pre-PGD work-up defines whether the carrier couple can benefit from this technology.

avatar for Rossa Chiu

Rossa Chiu

Professor, Department of Chemical Pathology, The Chinese University of Hong Kong
avatar for Diane Van Opstal

Diane Van Opstal

Laboratory Specialist Clinical Genetics, Erasmus Medical Center, Clinical Genetics
Diane Van Opstal studied Biology at the University of Leuven (Belgium) and  after her study, since 1987, she has worked in the Prenatal Cytogenetics Laboratory of the Department of Clinical Genetics at the Erasmus Medical Centre in Rotterdam. She received her Ph.D. (“Molecular... Read More →

avatar for Jia Ding

Jia Ding

Bioinformatician, UZ Leuven

Tuesday July 10, 2018 11:34 - 12:46 CEST
Queen Elisabeth Hall