First systematic experience of preimplantation genetic diagnosis for single-gene disorders, and/or preimplantation human leukocyte antigen typing, combined with 24-chromosome aneuploidy testing

Rechitsky, Svetlana; Pakhalchuk, Tatiana; Ramos, Geraldine San; Goodman, Adam; Zlatopolsky, Zev; Kuliev, Anver

doi:10.1016/j.fertnstert.2014.11.007

Cited by 77 publications

(74 citation statements)

References 18 publications

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“…However, separate procedures had to be used for each embryo (27). Moreover, the targeted mutations still could not be observed directly in these non-NGS methods (23).…”

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses

Yan

Huang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

119

114

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In vitro fertilization (IVF), preimplantation genetic diagnosis (PGD), and preimplantation genetic screening (PGS) help patients to select embryos free of monogenic diseases and aneuploidy (chromosome abnormality). Next-generation sequencing (NGS) methods, while experiencing a rapid cost reduction, have improved the precision of PGD/PGS. However, the precision of PGD has been limited by the false-positive and false-negative single-nucleotide variations (SNVs), which are not acceptable in IVF and can be circumvented by linkage analyses, such as short tandem repeats or karyomapping. It is noteworthy that existing methods of detecting SNV/copy number variation (CNV) and linkage analysis often require separate procedures for the same embryo. Here we report an NGS-based PGD/PGS procedure that can simultaneously detect a single-gene disorder and aneuploidy and is capable of linkage analysis in a cost-effective way. This method, called “mutated allele revealed by sequencing with aneuploidy and linkage analyses” (MARSALA), involves multiple annealing and looping-based amplification cycles (MALBAC) for single-cell whole-genome amplification. Aneuploidy is determined by CNVs, whereas SNVs associated with the monogenic diseases are detected by PCR amplification of the MALBAC product. The false-positive and -negative SNVs are avoided by an NGS-based linkage analysis. Two healthy babies, free of the monogenic diseases of their parents, were born after such embryo selection. The monogenic diseases originated from a single base mutation on the autosome and the X-chromosome of the disease-carrying father and mother, respectively.

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“…However, separate procedures had to be used for each embryo (27). Moreover, the targeted mutations still could not be observed directly in these non-NGS methods (23).…”

Section: Significancementioning

confidence: 99%

“…Several groups have reported the combined use of two or three of these methods in the same embryo to increase precision in the selection of embryos (25)(26)(27). Konstantinidis et al (23) reported a combined procedure of detecting chromosomal abnormality and linkage analysis using the karyomapping method.…”

mentioning

confidence: 99%

Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses

Yan

Huang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

119

114

View full text Add to dashboard Cite

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“…The methodology involved WGA from a single biopsied blastomere, followed by a multiplex nested PCR approach using a specific custom-made PGD design for each couple. This resulted in a decreased number of transferable embryos identified (the authors estimate the chance of identifying a transferable embryo between 6.25-9.4% depending on the monogenic condition diagnosed), but a higher pregnancy rate per embryo transfer in these cycles compared to HLA-PGD cycles performed without concurrent aneuploidy testing [Rechitsky et al 2015]. The usefulness of this approach could be further validated by collecting data from a greater number of cycles.…”

Section: Discussionmentioning

confidence: 99%

Complex preimplantation genetic diagnosis for beta-thalassaemia, sideroblastic anaemia, and human leukocyte antigen (HLA)-typing

Kakourou

Vrettou

Kattamis

et al. 2015

Systems Biology in Reproductive Medicine

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Preimplantation genetic diagnosis (PGD) to select histocompatible siblings to facilitate curative haematopoeitic stem-cell transplantation (HSCT) is now an acceptable option in the absence of an available human leukocyte antigen (HLA) compatible donor. We describe a case where the couple who requested HLA-PGD, were both carriers of two serious haematological diseases, beta-thalassaemia and sideroblastic anaemia. Their daughter, affected with sideroblastic anaemia, was programmed to have HSCT. A multiplex-fluorescent-touchdown-PCR protocol was optimized for the simultaneous amplification of: the two HBB-gene mutated regions (c.118C4T, c.25-26delAA), four short tandem repeats (STRs) in chr11p15.5 linked to the HBB gene, the SLC25A38 gene mutation (c.726C4T), two STRs in chr3p22.1 linked to the SLC25A38 gene, plus eleven informative STRs for HLA-haplotyping (chr6p22.1-21.3). This was followed by real-time nested PCR and high-resolution melting analysis (HRMA) for the detection of HBB and SLC25A38 gene mutations, as well as the analysis of all STRs on an automatic genetic analyzer (sequencer). The couple completed four clinical in vitro fertilization (IVF)/PGD cycles. At least one matched unaffected embryo was identified and transferred in each cycle. A twin pregnancy was established in the fourth PGD cycle and genotyping results at all loci were confirmed by prenatal diagnosis. Two healthy baby girls were delivered at week 38 of pregnancy. The need to exclude two familial disorders for HLA-PGD is rarely encountered. The methodological approach described here is fast, accurate, clinically-validated, and of relatively low cost.

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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%

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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First systematic experience of preimplantation genetic diagnosis for single-gene disorders, and/or preimplantation human leukocyte antigen typing, combined with 24-chromosome aneuploidy testing

Cited by 77 publications

References 18 publications

Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses

Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses

Complex preimplantation genetic diagnosis for beta-thalassaemia, sideroblastic anaemia, and human leukocyte antigen (HLA)-typing

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

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