scholarly journals Can expelled cells/debris from a developing embryo be used for PGT?

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Adva Aizer ◽  
Noa Harel-Inbar ◽  
Hagit Shani ◽  
Raoul Orvieto
Keyword(s):  
Zona Pellucida ◽  
Single Gene ◽  
Molecular Genetic ◽  
Embryo Biopsy ◽  
Human Embryos ◽  
Cell Debris ◽  
Preimplantation Genetic Testing ◽  
Blastomere Biopsy ◽  
Wide Range ◽  
Genetic Results

Abstract Background Preimplantation genetic testing (PGT) is offered to a wide range of structural and numerical chromosomal imbalances, with PGT- polymerase chain reaction (PCR), as the method of choice for amplifying the small DNA content achieved from the blastomere biopsy or trophectoderm (TE) biopsy, that might have a detrimental impact on embryonic implantation potential. Since human embryos cultured until Day-5–6 were noticed to expel cell debris/ fragments within the zona pellucida, we aimed to examine whether these cell debris/ fragments might be used for PGT, as an alternative to embryo biopsy. Methods Blastocysts, which their Day-3 blastomere biopsy revealed an affected embryo with single-gene defect, and following hatching leaved cell debris/fragments within the zona pellucida were analyzed. Each blastocyst and its corresponding cell debris/fragments were separated and underwent the same molecular analysis, based on multiplex PCR programs designed for haplotyping using informative microsatellites markers. The main outcome measure was the intra-embryo congruity of Day-3 blastomere biopsy and its corresponding blastocyst and cell debris/fragments. Results Fourteen affected embryos from 9 women were included. Only 8/14 (57.2%) of embryos demonstrated congruent molecular genetic results between Day-3 embryo and its corresponding blastocyst and cell debris/fragments. In additional 6/14 (42.8%) embryos, molecular results of the Day-3 embryos and their corresponding blastocysts were congruent, while the cell debris/fragments yielded no molecular diagnoses (incomplete diagnoses). Conclusions It might be therefore concluded, that in PGT cycles, examining the cell debris/fragments on Day-4, instead of Day-3 blastomere or Day-5 TE biopsies, is feasible and might avoid embryo biopsy with its consequent detrimental effect on embryos’ implantation potential. Whenever the latter results in incomplete diagnosis, TE biopsy should be carried out on Day-5 for final genetic results. Further large well-designed studies are required to validate the aforementioned PGT platform.

Epigenetics and Applied Anthropology

2021 ◽  
Author(s):  
Charles H. Klein
Keyword(s):  
Social Inequalities ◽  
Homo Sapiens ◽  
Single Gene ◽  
Molecular Genetic ◽  
Healthcare Providers ◽  
Basic Research ◽  
Sufficient Information ◽  
Theoretical Frameworks ◽  
Noncoding Dna ◽  
Wide Range

Since Francis Crick and James D. Watson’s discovery of DNA in 1953, researchers, policymakers, and the general public have sought to understand the ways in which genetics shapes human lives. A milestone in these efforts was the completion of the Human Genome Project’s (HGP) sequencing of Homo sapiens’ nearly three million base pairs in 2003. Yet, despite the excitement surrounding the HGP and the discovery of the structural genetic underpinnings of several debilitating diseases, the vast majority of human health outcomes have not been linked to a single gene. Moreover, even when genes have been associated with particular diseases (e.g., breast and colon cancer), it is not well understood why certain genetically predisposed individuals become ill and others do not. Nor has the HGP’s map provided sufficient information to understand the actual functioning of the human genetic code, including the role of noncoding DNA (“junk DNA”) in regulating molecular genetic processes. In response, a growing number of scientists have shifted their attention from structural genetics to epigenetics, the study of how genes express themselves in particular situations and environments. Anthropologists play roles in these applications of epigenetics to real-world settings. Their new theoretical frameworks unsettle the nature-versus-nurture binary and support biocultural anthropological research demonstrating how race becomes biology and embodies social inequalities and health disparities across generations. Ethnographically grounded case studies further highlight the diverse epigenetic logics held by healthcare providers, researchers, and patient communities and how these translations of scientific knowledge shape medical practice and basic research. The growing field of environmental epigenetics also offers a wide range of options for students and practitioners interested in applying the anthropological toolkit in epigenetics-related work.

scholarly journals ESHRE PGT Consortium good practice recommendations for the organisation of PGT†

2020 ◽  
Vol 2020 (3) ◽  
Author(s):  
Filipa Carvalho ◽  
Edith Coonen ◽  
Veerle Goossens ◽  
Georgia Kokkali ◽  
Carmen Rubio ◽  
...  
Keyword(s):  
Best Practice ◽  
Single Gene ◽  
Good Practice ◽  
Diagnostic Testing ◽  
Genetic Diagnosis ◽  
Information Provision ◽  
Embryo Biopsy ◽  
Preimplantation Genetic Testing ◽  
Gene Defects

Abstract The field of preimplantation genetic testing (PGT) is evolving fast, and best practice advice is essential for regulation and standardisation of diagnostic testing. The previous ESHRE guidelines on best practice for preimplantation genetic diagnosis, published in 2005 and 2011, are considered outdated and the development of new papers outlining recommendations for good practice in PGT was necessary. The current updated version of the recommendations for good practice is, similar to the 2011 version, split into four documents, one of which covers the organisation of a PGT centre. The other documents focus on the different technical aspects of embryo biopsy, PGT for monogenic/single-gene defects (PGT-M) and PGT for chromosomal structural rearrangements/aneuploidies (PGT-SR/PGT-A). The current document outlines the steps prior to starting a PGT cycle, with details on patient inclusion and exclusion, and counselling and information provision. Also, recommendations are provided on the follow-up of PGT pregnancies and babies. Finally, some further recommendations are made on the practical organisation of an IVF/PGT centre, including basic requirements, transport PGT and quality management. This document, together with the documents on embryo biopsy, PGT-M and PGT-SR/PGT-A, should assist everyone interested in PGT in developing the best laboratory and clinical practice possible.

Molecular genetic research on IQ: can it be done? Should it be done?

1996 ◽  
Vol 28 (4) ◽  
pp. 490-507 ◽  
Author(s):  
Jo Daniels ◽  
Peter McGuffin ◽  
Mike Owen
Keyword(s):  
Single Gene ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Cultural Factors ◽  
Shared Environment ◽  
Religious Denomination ◽  
Genetic Investigation ◽  
Genetic Studies ◽  
Single Gene Disorders ◽  
Wide Range

An obvious requirement before embarking on molecular genetic investigation of a trait is prior evidence from ‘classic’ genetic studies that there is indeed a genetic component. Many behavioural traits are familial and these range from comparatively uncommon single gene disorders such as Huntington's disease which has a typical mendelian dominant pattern of transmission, to much commoner characteristics such as career choice or religious denomination which, it might be assumed, are heavily influenced by cultural factors. In between, there is a wide range of attributes including personality type, cognitive ability and liability to common disorders such as depression, that show a tendency to run in families, and which could conceivably be explained by shared genes, shared environment or a combination of the two.

scholarly journals ESHRE PGT Consortium and SIG Embryology good practice recommendations for polar body and embryo biopsy for PGT†

2020 ◽  
Vol 2020 (3) ◽  
Author(s):  
Georgia Kokkali ◽  
Giovanni Coticchio ◽  
Fernando Bronet ◽  
Catherine Celebi ◽  
Danilo Cimadomo ◽  
...  
Keyword(s):  
Best Practice ◽  
Single Gene ◽  
Polar Body ◽  
Good Practice ◽  
Diagnostic Testing ◽  
Embryo Biopsy ◽  
Preimplantation Genetic Testing ◽  
Technical Aspects ◽  
Practice Recommendations ◽  
Blastocyst Biopsy

Abstract The field of preimplantation genetic testing (PGT) is evolving fast, and best practice advice is essential for regulation and standardisation of diagnostic testing. The previous ESHRE guidelines on best practice for PGD, published in 2005 and 2011, are considered outdated, and the development of new papers outlining recommendations for good practice in PGT was necessary. The current paper provides recommendations on the technical aspects of embryo biopsy and covers recommendations on the biopsy procedure, cryopreservation and laboratory issues and training, in addition to technical aspects and strengths and limitations specific for currently used techniques at different stages (polar body, cleavage stage and blastocyst biopsy). Furthermore, alternative sampling methods are briefly described.This paper is one of a series of four papers on good practice recommendations on PGT. The other papers cover the organisation of PGT, and the different technical aspects of PGT for monogenic/single-gene defects (PGT-M) and PGT for chromosomal structural rearrangements/aneuploidies (PGT-SR/PGT-A). Together, these papers should assist everyone interested in PGT in developing the best laboratory and clinical practice possible.

scholarly journals The Technological Advances in Embryo Selection and Genetic Testing: A Look Back at the Evolution of Aneuploidy Screening and the Prospects of Non-Invasive PGT

2021 ◽  
Vol 2 (1) ◽  
pp. 26-34
Author(s):  
Channing Burks ◽  
Kristin Van Heertum ◽  
Rachel Weinerman
Keyword(s):  
Genetic Testing ◽  
Subsequent Development ◽  
Embryo Selection ◽  
Human Embryos ◽  
Comparative Genomic ◽  
Aneuploidy Screening ◽  
Preimplantation Genetic Testing ◽  
Blastomere Biopsy ◽  
Non Invasive ◽  
Technological Advances

Since the birth of the first IVF baby, Louise Brown, in 1978, researchers and clinicians have sought ways to improve pregnancy outcomes through embryo selection. In the 1990s, blastomere biopsy and fluorescence in situ hybridization (FISH) were developed in human embryos for the assessment of aneuploidy and translocations. Limitations in the number of chromosomes that could be assayed with FISH lead to the development of comparative genomic hybridization (CGH); however, pregnancy rates overall were not improved. The later development of trophectoderm biopsy with comprehensive chromosome screening (CCS) technologies, as well as the subsequent development of next-generation sequencing (NGS), have shown much greater promise in improving pregnancy and live birth rates. Recently, many studies are focusing on the utilization of non-invasive preimplantation genetic testing (niPGT) in an effort to assess embryo ploidy without exposing embryos to additional interventions.

Is there still a rationale for non-invasive PGT-A by analysis of cell-free DNA released by human embryos into culture medium?

2021 ◽  
Vol 36 (5) ◽  
pp. 1186-1190
Author(s):  
Raoul Orvieto ◽  
Adva Aizer ◽  
Norbert Gleicher
Keyword(s):  
Culture Media ◽  
Chromosomal Rearrangements ◽  
Primary Source ◽  
Normal Pregnancy ◽  
Early Embryo ◽  
Human Embryos ◽  
Cell Debris ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna

Abstract Human embryos utilise an array of processes to eliminate the very high prevalence of aneuploid cells in early embryo stages. Human embryo self-correction was recently demonstrated by their ability to eliminate/expel abnormal blastomeres as cell debris/fragments. A whole genome amplification study has demonstrated that 63.6% of blastocysts expelled cell debris with abnormal chromosomal rearrangements. Moreover, 55.5% of euploid blastocysts expel aneuploid debris, strongly suggesting that the primary source of cell free DNA in culture media is expelled aneuploid blastomeres and/or their fragments. Such a substantial ability to self-correct downstream from the blastocyststage, therefore, renders any chromosomal diagnosis at the blastocyststage potentially useless, and this, unfortunately, also must particularly include non-invasive PGT-A based on cell-free DNA in spent medium. High rates of false-positive diagnoses of human embryos often lead to non-use and/or disposal of embryos with entirely normal pregnancy potential. Before adopting yet another round of unvalidated PGT-A as a routine adjunct to IVF, we here present facts that deserve to be considered.

scholarly journals Molecular genetics of bipolar disorder

2001 ◽  
Vol 178 (S41) ◽  
pp. s128-s133 ◽  
Author(s):  
Nick Craddock ◽  
Ian Jones
Keyword(s):  
Bipolar Disorder ◽  
Candidate Gene ◽  
Molecular Genetics ◽  
Ethical Issues ◽  
Association Studies ◽  
Single Gene ◽  
Molecular Genetic ◽  
Genetic Dissection ◽  
Adoption Studies ◽  
Candidate Gene Association

BackgroundA robust body of evidence from family, twin and adoption studies demonstrates the importance of genes in the pathogenesis of bipolar disorder. Recent advances in molecular genetics have made it possible to identify these susceptibility genes.AimsTo present an overview for clinical psychiatrists.MethodReview of current molecular genetics approaches and emerging findings.ResultsOccasional families may exist in which a single gene plays a major role in determining susceptibility, but the majority of bipolar disorder involves more complex genetic mechanisms such as the interaction of multiple genes and environmental factors. Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest include chromosomes 4p16, 12q23–q24, 16p13, 21q22, and Xq24–q26. Candidate gene association studies are in progress but no robust positive findings have yet emerged.ConclusionIt is almost certain that over the next few years the identification of bipolar susceptiblity genes will have a major impact on our understanding of disease pathophysiology. This is likely to lead to major improvements and treatment in patient care, but will also raise important ethical issues.

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