Chromosome analysis on DNA chip (CADC) or CGH-array

Screening for a chromosome abnormality belongs to the tests prescribed in first intention in the etiological check-up of development disorders in children or adults: intellectual deficiency, congenital abnormalities and pervasive behavioral disorders (autism, delayed language and related syndromes).
In total, those pathologies concern 5 to 14 % of the population. The discovery of a chromosome rearrangement will help managing the child and will enable genetic counseling for avoiding a potential recurrence.
The conventional karyotype, enabling a whole analysis of the genome with a 10 Mb (10 millions of base pairs) discovers an abnormality in 5% of the cases.
Molecular cytogenetics techniques (FISH) enable the discovery of 3 à 4% additional abnormalities. Yet, they are targeted techniques allowing the exploration of only a small amount of loci: sub-telomeric regions and loci of recurrent micro-deletional syndromes.
DNA chip techniques, or CGH-array or CGH on micro-network, have been developed over the last ten years and they are now fully validated for discovering the variations of copy numbers (CNV) in the context of intellectual disability and congenital abnormalities.
The CADC enables the study of the whole genome with a resolution ranging from 40 kilobases (40 000 base pairs) to 1 Mb depending on the technique, meaning 10 to 100-fold as compared to the karyotype. This technique discovers 15 to 20% of pathogenic CNV in patients with delayed development.
A CADC may be performed after a normal karyotype or in first intention.
We now offer this technique with the Affymetrix platform and the Cytoscan-HD chip. It is a SNP’s chip (single nucleotide polymorphisms) containing 2.5 millions probes with 1 label / 1 400 bases on the whole genome and an enhanced coverage (1 label / 380 to 650 bases) on the regions of interest, thus providing a resolution of 40 Kb for good quality DNAs. In addition, the SNP’s technique is the only one to enable the diagnosis of uni-parental disomy and to check the absence of inter-samples contaminations.
Validation of the pathogenic character of those very small size abnormalities requires from the cytogenetician specific skills in the interpretation of the genome data and the use of several international databases.
Abnormalities diagnosed in CADC are confirmed in FISH and/or PCR. A karyotype and FISH are performed in the parents to assess the mechanism of the abnormality and it de novo or inherited character in the purpose of genetic counseling.
Some rearrangements may be difficult to interpret and may require a CADC to be performed in the parents in order to assess if it is an inherited and probably non pathogenic abnormality or a causal rearrangement. The patient must be informed about the existence of such abnormalities of difficult interpretation. An information note for the patient and / or the parents is available on our website: DOWNLOAD
Limits of the technique: the CADC technique discovers only the imbalanced abnormalities and does not screen weak mozaiques.
It belongs to the investigations of the genetic characteristics requiring a consultation certificate and the patient’s consent.
No test will be performed in the absence of clinical information. Specific test request form available on our website: DOWNLOAD


Anne Bazin, Ph.D.
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