Shallow whole genome sequencing is well suited for the detection of chromosomal aberrations in human blastocysts.
OBJECTIVE
To add evidence that massive parallel sequencing (MPS) is a valuable substitute for array comparative genomic hybridization (arrayCGH) with a resolution that is more appropriate for preimplantation genetic diagnosis (PGD) in translocation carriers.


METHODS
Study of diagnostic accuracy.


METHODS
University hospital.


METHODS
Fifteen patients with a balanced structural rearrangement were included in the study: eight reciprocal translocations, four Robertsonian translocations, two inversions, and one insertional translocation.


METHODS
Trophectoderm biopsy was performed on 47 blastocysts.


METHODS
In the current study, shallow whole genome MPS on a NextSeq500 (Illumina) and Ion Proton (Life Technologies) instrument was performed in parallel on 47 whole genome amplified trophectoderm samples. Data analyses were performed using the QDNAseq algorithm implemented in Vivar.


RESULTS
In total, 5 normal and 42 abnormal embryos were analyzed. All aberrations previously detected with arrayCGH could be readily detected in the MPS data using both technologies and were correctly identified. The smallest detected abnormality was a ∼ 4.5 Mb deletion/duplication.


CONCLUSIONS
This study demonstrates that shallow whole genome sequencing can be applied efficiently for the detection of numerical and structural chromosomal aberrations in embryos, equaling or even exceeding the resolution of the routinely used microarrays.
Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.
Lieselot
L
Deleye
Center for Medical Genetics, Ghent University, Ghent, Belgium.
Annelies
A
Dheedene
Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.
Dieter
D
De Coninck
Center for Medical Genetics, Ghent University, Ghent, Belgium.
Tom
T
Sante
Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium.
Christodoulos
C
Christodoulou
Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium.
Björn
B
Heindryckx
Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium.
Etienne
E
Van den Abbeel
Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium.
Petra
P
De Sutter
Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.
Dieter
D
Deforce
Center for Medical Genetics, Ghent University, Ghent, Belgium. Electronic address: Bjorn.Menten@ugent.be.
Björn
B
Menten
Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.
Filip
F
Van Nieuwerburgh
D000328:Adult; D001706:Biopsy; D001755:Blastocyst / Q000473:pathology*; D025063:Chromosome Disorders / Q000235:genetics* / Q000473:pathology; D002877:Chromosomes, Human / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D046149:Embryo Culture Techniques; D005260:Female; D005819:Genetic Markers; D059014:High-Throughput Nucleotide Sequencing; D006785:Hospitals, University; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D019836:Preimplantation Diagnosis / Q000379:methods*; D020554:Sperm Injections, Intracytoplasmic; D014178:Translocation, Genetic
D005819:Genetic Markers
Massive parallel sequencing; blastocyst biopsy; chromosomal rearrangements; preimplantation genetic diagnosis; whole genome amplification