Genomic Arrays in Prenatal Diagnosis

Abstract

Prenatal diagnosis (PND) is being applied to high‐risk pregnancies in order to identify possible genetic disorders in an unborn foetus or embryo. Through the application of various techniques, genetic disorders can be detected. As chromosomal abnormalities are one of the major causes of childhood intellectual disability and first trimester intrauterine deaths, PND is often suggested to exclude genetic disorders caused by chromosomal abnormalities. Currently, chromosomal analysis is the method of choice in PND, but with the emerging technologies, its substitution to array comparative genomic hybridisation (array‐CGH), is being considered. Challenges such as, interpretation issues, limitations of the method and lack of a dedicated database for prenatal samples that correlates ultrasound findings to copy number changes, need to be overcome before conventional karyotyping can be replaced by array‐CGH in PND.

Key Concepts

  • Prenatal diagnosis is applied to high‐risk pregnancies.
  • Invasive prenatal diagnosis is required to exclude genetic disorders in the foetus.
  • Chromosomal analysis, a whole genome testing, is used to detect chromosomal abnormalities in prenatal diagnosis.
  • Noninvasive prenatal screening tests can be offered to all pregnant women.
  • Complementary methods to chromosomal analysis can be applied to offer rapid prenatal testing for certain conditions.
  • Array‐CGH, a whole genome diagnostic test can be offered to add diagnostic value to chromosomal analysis.

Keywords: array comparative genomic hybridisation (array‐CGH); chromosomal analysis; karyotype; prenatal diagnosis; copy number variation (CNV)

Figure 1. A normal male G‐Banded karyotype from an amniotic fluid at between 550‐850 bands per haploid set resolution.
Figure 2. Array‐CGH analysis of a prenatal case presented with tetralogy of Fallot, showing a causative de novo copy number loss on the short arm of chromosome 19 at 19p13.3. Representation of the chromosomal and genomic location region [113,447–1,035,371 (GRCh37,hg19)] in the Database of Genomic Variants is shown. The loss of 700–950 Kb in size is marked by the red arrows, and it encompasses several RefSeq genes; four OMIM disease genes included in the deletion are represented by the orange bracket namely BSG, ELANE, CFD, KISS1R.
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Evangelidou P, Patsalis CP and Sismani C (2015) Array in prenatal diagnosis. In: Henderson A (ed.) Prenatal and Maternal Diagnosis, Screening and Infant Development Implications, pp. 53–107. New York, NY: Nova Science Publishers, Inc.

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Evangelidou, Paola, and Sismani, Carolina(Mar 2017) Genomic Arrays in Prenatal Diagnosis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026715]