68. PREIMPLANTATION GENETIC TESTING OF MONOGENIC DISEASE: EXPERIENCE IN RUSSIA

2019 ◽  
Vol 39 ◽  
pp. e68-e69
Author(s):  
S. Zhikrivetskaya Olegovna ◽  
Y. Volkova Leonidovna ◽  
E. Musatova Valerievna ◽  
Y. Sofronova Vladislavovna ◽  
N. Shirokova Anatolievna ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Monogenic Disease ◽  
Preimplantation Genetic Testing ◽  
Disease Experience

scholarly journals Haplotyping by linked-read sequencing (HLRS) of the genetic disease carriers for preimplantation genetic testing without a proband or relatives

2020 ◽  
Author(s):  
Qing Li ◽  
Yan Mao ◽  
Shaoying Li ◽  
Hongzi Du ◽  
Wenzhi He ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Genetic Disease ◽  
De Novo ◽  
Monogenic Disease ◽  
Nucleotide Polymorphisms ◽  
De Novo Mutations ◽  
Preimplantation Genetic Testing ◽  
Linkage Analyses ◽  
Alpha Thalassemia ◽  
Polar Bodies

Abstract Background: In order to mitigate the risk of allele dropout (ADO) and ensure the accuracy of preimplantation genetic testing for monogenic disease (PGT-M), it is necessary to construct parental haplotypes.. Typically, haplotype resolution is obtained by genotyping multiple polymorphic markers in both parents and a proband or a relative. Sometimes, single sperm typing, or tests on the polar bodies may also be useful. Nevertheless, this process is time-consuming. At present, there was no simple linkage analysis strategy for patients without affected relatives.Method: To solve this problem, we established a haplotyping by linked-read sequencing (HLRS) method without the requirement for additional relatives. First, the haplotype of the genetic disease carriers in the family was constructed by linked-read sequencing, and then the informative single nucleotide polymorphisms (SNPs) in upstream and downstream mutation region were selected to construct the embryo haplotype and to determine whether the embryo was carrying the mutation. Two families were selected to validate this method; one with alpha thalassemia and the other with NDP gene disorder.Results: The haplotyping by linked-read sequencing (HLRS) method was successfully applied to construct parental haplotypes without recruiting additional family members; the method was also validated for PGT-M. The mutation carriers in these families were sequenced by linked-read sequencing, and their haplotypes were successfully phased. Adjacent SNPs of the mutation gene were identified. The informative SNPs were chosen for linkage analyses to identify the carrier embryos. For the alpha thalassemia family, a normal blastocyst was transferred to the uterus and the accuracy of PGT-M was confirmed by amniocentesis at 16 weeks of gestation. Conclusions: Our results suggest that HLRS can be applied for PGT-M of monogenic disorders or de novo mutations where the mutations haplotype cannot be determined due to absence of affected relatives. Keywords: Preimplantation Genetic Testing for monogenic disease, Linked-read sequencing, Linkage analyses, Haplotype

scholarly journals PREIMPLANTATION GENETIC TESTING: Preimplantation genetic testing for polygenic disease risk

Reproduction ◽  
2020 ◽  
Vol 160 (5) ◽  
pp. A13-A17 ◽  
Author(s):  
Nathan R Treff ◽  
Diego Marin ◽  
Louis Lello ◽  
Stephen Hsu ◽  
Laurent C A M Tellier
Keyword(s):  
Clinical Practice ◽  
Genetic Testing ◽  
Disease Risk ◽  
Population Level ◽  
Standard Of Care ◽  
Primary Objective ◽  
Monogenic Disease ◽  
Preimplantation Genetic Testing ◽  
Polygenic Disease ◽  
Risk Scoring

Since its introduction to clinical practice, preimplantation genetic testing (PGT) has become a standard of care for couples at risk of having children with monogenic disease and for chromosomal aneuploidy to improve outcomes for patients with infertility. The primary objective of PGT is to reduce the risk of miscarriage and genetic disease and to improve the success of infertility treatment with the delivery of a healthy child. Until recently, the application of PGT to more common but complex polygenic disease was not possible, as the genetic contribution to polygenic disease has been difficult to determine, and the concept of embryo selection across multiple genetic loci has been difficult to comprehend. Several achievements, including the ability to obtain accurate, genome-wide genotypes of the human embryo and the development of population-level biobanks, have now made PGT for polygenic disease risk applicable in clinical practice. With the rapid advances in embryonic polygenic risk scoring, diverse considerations beyond technical capability have been introduced.

scholarly journals Combined Preimplantation Genetic Testing for Aneuploidy and Monogenic Disease in a Mexican Family Affected by X-linked Hypohidrotic Ectodermal Dysplasia

2018 ◽  
Vol 70 (4) ◽  
Author(s):  
Raul Eduardo Piña-Aguilar ◽  
Claudia González-Ortega ◽  
Anna Calull-Bago ◽  
María Cristina Lanuza-López ◽  
Patricia Cancino-Villarreal ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Ectodermal Dysplasia ◽  
Monogenic Disease ◽  
Hypohidrotic Ectodermal Dysplasia ◽  
Preimplantation Genetic Testing ◽  
Mexican Family

scholarly journals Patients’ preimplantation genetic testing decision-making experience: an opinion on related psychological frameworks

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
L M Pastore ◽  
C N Cordeiro Mitchell ◽  
L R Rubin ◽  
J Nicoloro-SantaBarbara ◽  
M C Genoff Garzon ◽  
...  
Keyword(s):  
Decision Making ◽  
Genetic Testing ◽  
Conceptual Framework ◽  
Psychological Theory ◽  
Well Being ◽  
Situational Factors ◽  
Monogenic Disease ◽  
Patient Counseling ◽  
Contributing Factors ◽  
Preimplantation Genetic Testing

Abstract The process of deciding whether to pursue preimplantation genetic testing (PGT) of an embryo is highly stressful for individuals and couples and has adverse emotional consequences (e.g. distress and uncertainty). PGT influences patients’ lives in both positive and negative ways and is experienced at an individual level, as a dyadic unit, as a family member and as part of the society. Here, we argue that providing a conceptual framework with which to understand the `experience of decision making’ about PGT for monogenic disease (PGT-M) testing specifically, as well as the factors contributing to `decisional distress’ and `uncertainty’ that patients endure as a result—apart from what decision they make—is crucial to optimizing patient counseling, satisfaction and outcomes in the field of ART. Derived from psychological theory, the framework proposed here identifies three categories of contributing factors to decisional distress and uncertainty in considering PGT-M; namely, ‘intraindividual’, ‘interpersonal’ and ‘situational’ factors. We reviewed evidence from the PGT literature to inform our framework. Well-accepted theories of stress and health decision making were also reviewed for their relevance to PGT-M decision making, focusing on potential distress and uncertainty. Our novel conceptual framework can be used to inform clinical practice, to advance research and to aid the development of interventions for individuals and couples who are deciding whether or not to use PGT-M. Alleviating emotional distress and uncertainty can improve patients’ well-being during their reproductive journey.

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