Oligonucleotide microarrays in constitutional genetic diagnosis

Abstract

Oligonucleotide microarrays such as comparative genomic hybridization arrays and SNP microarrays enable the identification of genomic imbalances – also termed copy-number variants – with increasing resolution. This article will focus on the most significant applications of high-throughput oligonucleotide microarrays, both in genetic diagnosis and research. In genetic diagnosis, the method is becoming a standard tool for investigating patients with unexplained developmental delay/intellectual disability, autism spectrum disorders and/or with multiple congenital anomalies. Oligonucleotide microarray have also been recently applied to the detection of genomic imbalances in prenatal diagnosis either to characterize a chromosomal rearrangement that has previously been identified by standard prenatal karyotyping or to detect a cryptic genomic imbalance in a fetus with ultrasound abnormalities and a normal standard prenatal karyotype. In research, oligonucleotide microarrays have been used for a wide range of applications, such as the identification of new genes responsible for monogenic disorders and the association of a copy-number variant as a predisposing factor to a common disease. Despite its widespread use, the interpretation of results is not always straightforward. We will discuss several unexpected results and ethical issues raised by these new methods.

Keywords::

• array
• comparative genomic hybridization
• copy number variant
• genetic diagnosis
• genomic imbalance
• mental retardation
• prenatal diagnosis

Acknowledgements

We thank Olivier Pichon, Annaig Briand and Damien Poulain for technical assistance; Rémi Houlgatte and Catherine Chevalier from Biogenouest de Nantes.

Financial & competing interests disclosure

This research was funded by the Direction Générale de l’Organisation des Soins (DGOS). Cedric Le Caignec is supported by the Centre Hospitalier Universitaire de Nantes and the University de Nantes, France. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.