J Korean Med Assoc.  2015 Nov;58(11):979-988. 10.5124/jkma.2015.58.11.979.

Preimplantation genetic diagnosis

• Kim JY
• Lee HS
• Kang IS

• KMID: 2195126
• DOI: http://doi.org/10.5124/jkma.2015.58.11.979

Abstract

Preimplantation genetic diagnosis (PGD) is a technique to examine genetic disease or chromosome abnormalities in single cell biopsied from embryos before implantation to uterus. It allows achieving normal pregnancy by transfer of unaffected embryos. The main indications are single gene disorders and recurrent miscarriage related to chromosome aberration and it has advantages to avoid termination of pregnancy or miscarriages in couples with high risk. PGD is also widely applied for aneuploidy screening in assisted reproduction to improve the outcome in infertile patients such as advanced maternal age, although its efficacy still needs to be established. Furthermore, the application of PGD has expanded to other indications, such as late onset-diseases with genetic predisposition and human leukocyte antigen typing for stem cell transplantation. With the advances of molecular diagnostic technologies using single cells, such as fluorescent in situ hybridization, multiplex polymerase chain reaction, fluorescent polymerase chain reaction, linkage analysis, whole genome amplification, array comparative genomic hybridization (array comparative genomic hybridization), and next generation sequencing, PGD can provide more comprehensive and reliable diagnosis.

Keyword

Preimplantation diagnosis; Genetic disorder; Polymerase chain reaction; Comparative genomic hybridization; Next generation sequencing

MeSH Terms

Abortion, Habitual
Abortion, Spontaneous
Aneuploidy
Chromosome Aberrations
Comparative Genomic Hybridization
Diagnosis
Embryonic Structures
Family Characteristics
Female
Genetic Predisposition to Disease
Genome
Humans
In Situ Hybridization, Fluorescence
Leukocytes
Mass Screening
Maternal Age
Multiplex Polymerase Chain Reaction
Pathology, Molecular
Polymerase Chain Reaction
Pregnancy
Preimplantation Diagnosis*
Prostaglandins D
Reproduction
Stem Cell Transplantation
Uterus
Prostaglandins D

Figure

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  Figure 1 Blastomere biopsy with acid Tyrode's solution or laser in cleavage stage embryo. (A) Position cleavage stage embryo on holding pipette. (B) Zona opening for cleavage stage embryo has been performed by acid Tyrodes or laser. (C,D) Removal of blastomeres by aspiration.

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  Figure 2 Direct sequencing of the polymerase chain reaction product spanning exon 37 in the preimplantation genetic diagnosis for osteogenesis imperfecta. (A) Normal male partner showing G/G sequence, (B) affected female partner demonstrating heterozygous G>A transition, (C) normal embryo showing G/G sequence, and (D) abnormal embryo showing G/A transition (From Kim MJ, et al. Korean J Reprod Med 2008;35:99-110, according to the Creative Commons license) [13].

• 

  Figure 3 Preimplantation genetic diagnosis for Charcot-Marie-Tooth disease by using duplex nested polymerase chain reaction and multiplex-fluorescent-polymerase chain reaction with linked marker. Arrows indicate polymorphic markers linked with affected allele (From Lee HS, et al. Clin Exp Reprod Med 2013;40:163-168, according to the Creative Commons license) [17].

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  Figure 4 Example of array comparative genomic hybridization based preimplantation genetic diagnosis result from aneuploidy embryos with trisomy 21. Arrow indicates chromosomal imbalance of a shift of the clones towards the green line (gain).

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  Figure 5 Aneuploidy analysis of cells biopsied from a human blastocyst. (A) Analysis of embryo using next generation sequencing predicting a female trisomic for chromosome 21. (B) Microarray comparative genomic hybridization analysis confirming the next generation sequencing result (From Wells D, et al. J Med Genet 2014;51:553-562, according to the Creative Commons license) [28].

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