Читать книгу Genetic Disorders and the Fetus - Группа авторов - Страница 71

Anver Kuliev and Svetlana Rechitsky

Herbert Wertheim College of Medicine, Florida International University, Miami, FL and Reproductive Genetic Innovations, Northbrook, IL, USA

Preimplantation genetic testing (PGT¹) is a practical option for couples at risk of having offspring with serious/fatal chromosomal or monogenic diseases. It has been used for up to 600 monogenic disorders (PGT‐M¹). Moreover, it has been used for human leukocyte antigen (HLA) typing (PGT‐HLA¹), enabling the births of many children whose matched bone marrows have proved life‐saving for siblings with congenital and acquired disorders requiring stem cell transplantation treatment.

Analysis of single cells or a few cells with a limited amount of available DNA has always presented a technical challenge, especially when PGT is faced with the need for accurate and rapid results from whole‐genome amplification (WGA), followed by polymerase chain reaction (PCR) assays that are robust and sensitive. Next‐generation sequencing (NGS) has allowed for accurate identification and transfer of euploid embryos (PGT for aneuploidies (PGT‐A)¹).

PGT‐M was initially applied for the same indications as prenatal diagnosis,^2–4 but was then expanded to conditions that had never been considered, such as late‐onset diseases with genetic predisposition and preimplantation HLA typing with or without testing for genetic disorders.^5–7

PGT represents a natural evolution of the genetic disease prevention technology, from a period with limited genetic counseling and no prenatal diagnosis or treatment to a time when many options, including PGT, have become available.⁸ Furthermore, PGT has been applied in order to improve access to the new treatment methods for some severe conditions by stem cell transplantation, for which no traditional treatment approaches are available. The impact of PGT and stem cell treatment on existing policies for the prevention of genetic disease (see Chapter 36) is clear from the increasing use of PGT to avoid unnecessary termination of many wanted pregnancies and for preimplantation HLA typing.