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Prenatal and pre-implantation genetic diagnosis


The past decade has seen the development of technologies that have revolutionized prenatal genetic testing; that is, genetic testing from conception until birth. Genome-wide single-cell arrays and high-throughput sequencing analyses are dramatically increasing our ability to detect embryonic and fetal genetic lesions, and have substantially improved embryo selection for in vitro fertilization (IVF). Moreover, both invasive and non-invasive mutation scanning of the genome are helping to identify the genetic causes of prenatal developmental disorders. These advances are changing clinical practice and pose novel challenges for genetic counselling and prenatal care.

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Figure 1: Timeline of prenatal and pre-implantation genetic diagnostics.
Figure 2: Cell-free fetal DNA aneuploidy screening methods.
Figure 3: Pre-implantation genetic diagnosis and screening.
Figure 4: Principles for pre-implantation genetic diagnosis using single-cell haplotyping.


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Corresponding author

Correspondence to Joris Robert Vermeesch.

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Competing interests

J.R.V. and T.V. are co-inventors on patent application ZL913096-PCT/EP2014/068315-WO/2015/028576 'Haplotyping and copy-number typing using polymorphic variant allelic frequencies', which is licensed to Cartagenia (Agilent Technologies).

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Allele drop out

(ADO). The failure to detect an allele in a sample or the failure to amplify an allele.


Cells of the fetus that are suspended in the amniotic fluid.


The presence of abnormal numbers of chromosomes in a cell. In human cells, this is typically when a cell contains either 45 or 47 chromosomes, instead of the expected 46.

Assisted reproductive techniques

Clinical approaches that are used to help infertile couples achieve a normal pregnancy. These include ovarian stimulation protocols using exogenous hormones, in vitro fertilization, intracytoplasmic sperm injection and pre-implantation genetic diagnosis.

B allele frequency

(BAF). A metric that is used to analyse the data derived from single-nucleotide polymorphism genotyping platforms and is defined as the proportion of allele B occurrence compared with the total allele A and allele B occurrences.


A blastocyst is a specific stage in embryonic development. On day 5 post fertilization the structure comprises a cavity, the blastocoel, with an inner cell mass; that is, the cells that subsequently contribute to the embryo and also extra-embryonic structures surrounded by a layer of trophoblast cells that provide the fetal component of the placenta.


Cells produced by cleavage of the zygote after fertilization.

Breakage–fusion–bridge cycles

Mechanisms of chromosome instability involving repeated cycles of telomeric breakage and fusion of the sister chromatids. As a consequence, the fused sister chromatids are pulled towards opposite poles during anaphase and are broken apart creating new breakpoints.


A condition in which an organism contains genetically distinct cell lines (that is, different parental genomes).

Chorionic villi

Villi that sprout from the chorion in the placenta to provide maximum contact area with maternal blood, allowing for efficient exchange of gasses and nutrients needed for fetal development.

Chromosomal instability

(CIN). An elevated rate of chromosome missegregation or breakage per cell division leading to aneuploidy or segmental aneuploidy.


The determination of the set of alleles for consecutive loci that are present on the same chromosome.


A condition in which an organism contains cell lines with different ploidy levels (for example, diploid and triploid).

Molar pregnancies

Pregnancies in which the trophoblast proliferates like a non-cancerous tumour and grows into a swollen chorionic villi mass in the uterus known as a hydatidiform mole.


The conditional probability of a phenotype (specifically, the probability of being affected with disease) given an underlying genotype.

Polar body

During oogenesis the primary and secondary oocyte divide asymmetrically; that is, most of the cytoplasm is segregated into one daughter cell (which becomes the egg or ovum) and the remaining cytoplasm goes to the smaller polar bodies. In humans, the first polar body is formed following the first meiotic division of the primary oocyte (which occurs near ovulation), and a second polar body is formed following the second meiotic division of the secondary oocyte (which occurs with fertilization).

Read pairs

In paired-end sequencing, a technology in which both ends of a short linear DNA molecule are sequenced, read pairs are mapped to a reference genome with a discordant orientation or distance between them, which can pinpoint structural variants.

Trisomy rescue

A phenomenon in a trisomic zygote (which contains three copies of one chromosome) in which aneuploidy is corrected by the loss of the additional chromosome during cell division. Owing to the random loss of the extra chromosome, the resulting daughter cell might contain two copies of a chromosome from the same parent (uniparental disomy).


Cells of the outer layer of a blastocyst, which provide nutrients to the embryo and develop into the fetal part of the placenta.

Uniparental disomy

(UPD). The presence of two copies of a chromosome, or part of a chromosome, from one parent and no copy from the other parent.

Whole-exome sequencing

(WES). The isolation and subsequent sequencing of the fraction of the genome that consists of protein-coding sequences (the so-called exonic sequences). The isolation is performed by capturing the exonic segments using complementary oligonucleotides as bait.

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Vermeesch, J., Voet, T. & Devriendt, K. Prenatal and pre-implantation genetic diagnosis. Nat Rev Genet 17, 643–656 (2016).

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