Development and validation of concurrent preimplantation genetic diagnosis for single gene disorders and comprehensive chromosomal aneuploidy screening without whole genome amplification

Zimmerman, Ryan M.; Jalas, Chaim; Tao, Xin; Fedick, Anastasia; Kim, Julia G.; Pepe, Russell J.; Northrop, Lesley E.; Scott, Richard T.; Treff, Nathan R.

doi:10.1016/j.fertnstert.2015.10.003

Cited by 41 publications

(24 citation statements)

References 23 publications

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“…This strategy reduced the necessary read depth for accurate sequencing of the mutation site as well as parallel RT-qPCR for chromosome copy number, which allows for a reduction in per sample cost as well as the time required to run the test [36]. Zimmerman and colleagues determined that this strategy was more reliable than other techniques [109] with 303/304 (99.7%) embryos getting a definitive diagnosis and 1/304 (0.3%) recorded as inconclusive due to a recombination event. This study also demonstrated an 82% (27/33) pregnancy rate [109].…”

Section: Simultaneous Detection Of Monogenic Disorders and Chromosomementioning

confidence: 99%

“…Zimmerman and colleagues determined that this strategy was more reliable than other techniques [109] with 303/304 (99.7%) embryos getting a definitive diagnosis and 1/304 (0.3%) recorded as inconclusive due to a recombination event. This study also demonstrated an 82% (27/33) pregnancy rate [109]. analysis [110].…”

Section: Simultaneous Detection Of Monogenic Disorders and Chromosomementioning

confidence: 99%

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Karyomapping and how is it improving preimplantation genetics?

Gould

Griffin

2017

Expert Review of Molecular Diagnostics

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Introduction: Preimplantation genetic diagnosis and screening (PGD/PGS) has been applied clinically for >25 years however inherent drawbacks include the necessity to tailor each case to the trait in question, and that technology to detect monogenic and chromosomal disorders respectively is fundamentally different.Areas Covered: The area of preimplantation genetics has evolved over the last 25 years, adapting to changes in technology and the need for more efficient, streamlined diagnoses. Karyomapping allows the determination of inheritance from the (grand)parental haplobocks through assembly of inherited chromosomal segments. The output displays homologous chromosomes, crossovers and the genetic status of the embryos by linkage comparison, as well as chromosomal disorders. It also allows for determination of heterozygous SNP calls, avoiding the risks of allele dropout, a common problem with other PGD techniques. Manuscripts documenting the evolution of preimplantation genetics, especially those investigating technologies that would simultaneously detect monogenic and chromosomal disorders, were selected for review.Expert Commentary: Karyomapping is currently available for detection of single gene disorders; ~1000 clinics worldwide offer it (via ~20 diagnostic laboratories) and ~2500 cases have been performed. Due an inability to detect post-zygotic trisomy reliably however and confounding problems of embryo mosaicism, karyomapping has yet to be applied clinically for detection of chromosome disorders.

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Section: Simultaneous Detection Of Monogenic Disorders and Chromosomementioning

confidence: 99%

Section: Simultaneous Detection Of Monogenic Disorders and Chromosomementioning

confidence: 99%

Karyomapping and how is it improving preimplantation genetics?

Gould

Griffin

2017

Expert Review of Molecular Diagnostics

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“…Briefly, to detect single gene disorder, the use of short tandem repeats (STRs) analysis has been complemented by novel technologies based on the use single-nucleotide polymorphism (SNP), such as SNP-array to conduct linkage based analysis or qPCR approach to detect the mutation and flanking informative SNPs by TaqMan genotyping [34][35][36]. To analyse the unbalanced products of translocation, inversion, or other abnormalities of the parental karyotype and de novo aneuploidies, we moved from traditional cytogenetics techniques as fluorescence in situ hybridization (FISH), which is able to analyse just few chromosomes with a considerable error rate [37] to 24-chromosome testing technologies.…”

Section: Selecting the Genetic Technologies For Genetic Testingmentioning

confidence: 99%

“…This is an additional possibility as in most cases, the women from couples that require PGD are of advanced reproductive age, thus presenting also an increased risk for embryonic aneuploidies. Remarkably, simultaneously PGD-A and PGD can be done on the same biopsy, within 4-6 h and in a cost-effective way [36]. Moreover, such a low turnaround time makes qPCR also compatible with fresh embryo transfer.…”

Section: Selecting the Genetic Technologies For Genetic Testingmentioning

confidence: 99%

Implementing PGD/PGD-A in IVF clinics: considerations for the best laboratory approach and management

Capalbo

Romanelli²,

Cimadomo

et al. 2016

J Assist Reprod Genet

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For an IVF clinic that wishes to implement preimplantation genetic diagnosis for monogenic diseases (PGD) and for aneuploidy testing (PGD-A), a global improvement is required through all the steps of an IVF treatment and patient care. At present, CCS (Comprehensive Chromosome Screening)-based trophectoderm (TE) biopsy has been demonstrated as a safe, accurate and reproducible approach to conduct PGD-A and possibly also PGD from the same biopsy. Key challenges in PGD/PGD-A implementation cover genetic and reproductive counselling, selection of the most efficient approach for blastocyst biopsy as well as of the best performing molecular technique to conduct CCS and monogenic disease analysis. Three different approaches for TE biopsy can be compared. However, among them, the application of TE biopsy approaches, entailing the zona opening when the expanded blastocyst stage is reached, represent the only biopsy methods suited with a totally undisturbed embryo culture strategy (time lapse-based incubation in a single media). Moreover, contemporary CCS technologies show a different spectrum of capabilities and limits that potentially impact the clinical outcomes, the management and the applicability of the PGD-A itself. In general, CCS approaches that avoid the use of whole genome amplification (WGA) can provide higher reliability of results with lower costs and turnaround time of analysis. The future perspectives are focused on the scrupulous and rigorous clinical validations of novel CCS methods based on targeted approaches that avoid the use of WGA, such as targeted next-generation sequencing technology, to further improve the throughput of analysis and the overall cost-effectiveness of PGD/PGD-A.

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“…The other strategy for reducing the ADO rate reported is a qPCR-based method. Previous studies demonstrate that qPCR-based PGD utilizing TaqMan assay revealed 0-0.3% ADO with 99.7-100% success rate for providing the diagnosis of monogenic disorders in the embryos [20]. Establishing a qPCR-based PGD is also intriguing for future clinical use.…”

Section: Preimplantation Genetic Diagnosis Protocolmentioning

confidence: 99%

First successful trial of preimplantation genetic diagnosis for pantothenate kinase-associated neurodegeneration

Trachoo

Satirapod

Panthan

et al. 2016

J Assist Reprod Genet

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Purpose We aim to present a case of a healthy infant born after intracytoplasmic sperm injection-in vitro fertilization (ICSI-IVF) with a preimplantation genetic diagnosis (PGD) for pantothenate kinase-associated neurodegeneration (PKAN) due to PANK2 mutation. Methods ICSI-IVF was performed on a Thai couple, 34-yearold female and 33-year-old male, with a family history of PKAN in their first child. Following fertilization, each of the embryos were biopsied in the cleavage stage and subsequently processed for whole-genome amplification. Genetic status of the embryos was diagnosed by linkage analysis and direct mutation testing using primer extension-based mini-sequencing. Comprehensive chromosomal aneuploidy screening was performed using a next-generation sequencing-based strategy.Results Only a single cycle of ICSI-IVF was processed. There were seven embryos from this couple-two were likely affected, three were likely carriers, one was likely unaffected, and one failed in target genome amplification. Aneuploidy screening was performed before making a decision on embryo transfer, and only one unaffected embryo passed the screening. That embryo was transferred in a frozen thawed cycle, and the pregnancy was successful. The diagnosis was confirmed by amniocentesis, which presented with a result consistent with PGD. At 38 weeks of gestational age, a healthy male baby was born. Postnatal genetic confirmation was also consistent with PGD and the prenatal results. At the age of 24 months, the baby presented with normal growth and development lacking any neurological symptoms. Conclusions We report the first successful trial of PGD for PKAN in a developing country using linkage analysis and mini-sequencing in cleavage stage embryos.

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Development and validation of concurrent preimplantation genetic diagnosis for single gene disorders and comprehensive chromosomal aneuploidy screening without whole genome amplification

Cited by 41 publications

References 23 publications

Karyomapping and how is it improving preimplantation genetics?

Karyomapping and how is it improving preimplantation genetics?

Implementing PGD/PGD-A in IVF clinics: considerations for the best laboratory approach and management

First successful trial of preimplantation genetic diagnosis for pantothenate kinase-associated neurodegeneration

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