Genome-wide deletion and duplication analysis

By detecting microdeletions and microduplications in a patient’s genome, array CGH analysis is able to detect significantly smaller abnormalities than conventional chromosome analysis. Conventional chromosome analysis detects a structural genomic alteration in only about 3 to 4 percent of the patients with developmental delays examined. A slight improvement in the detection rate can be achieved by molecular cytogenetic methods such as fluorescence in situ hybridization, or FISH. By using FISH diagnostics, predetermined targeted regions of the genome are analyzed for microdeletion and microduplication syndromes. Array CGH analysis detects the entire genome and can thus reveal significantly more changes in the genome. Array CGH analysis can thus detect causative alterations in up to 15% of patients. Array CGH analysis can resolve unclear cases of mental retardation or rare syndromic conditions. In addition, losses or gains detected in chromosomal analysis can be characterized more precisely, providing a much better indication of clinical relevance (genotype-phenotype correlation).

• 1-2 ml EDTA blood or 1-2 µg of genomic DNA
• Order Form
• Processing Time: 2–4 weeks

Array CGH analysis is a molecular genetic method that can be used to detect small gains or losses in chromosomal material below the detection limit of conventional chromosomal analysis. In array-based comparative genomic hybridization (CGH), patient DNA samples and a reference DNA are labeled with different fluorescent dyes and cohybridized on a carrier chip with immobilized DNA fragments (probes). These probes cover the human genome as uniformly as possible. Numerical changes result in a color shift of the fluorescence signal for the individual probes. These signals are detected by a laser scanner and assigned to the respective chromosomal region, and displayed using appropriate software (“molecular karyotyping”).

At CeGaT, all available array formats from Agilent can be processed, analyzed, and diagnosed. In routine, we use the Agilent 180K array with a diagnostic resolution of ≥50kb.

After the consultation, it is also possible to analyze individual high-resolution arrays.

For many diagnostic questions, array CGH has become the “first-line” method to clarify the cause.

In particular, the use of array CGH is indicated in the following cases:

• unclear mental retardation (IQ<70)
• Suspicion of changes from the autism spectrum
• functional disorders or malformations affecting the brain
• dysmorphic abnormalities
• congenital malformations of unclear etiology
• prenatal ultrasound abnormalities
• growth retardation or abnormalities (pre-or postnatal)

or

• for a more precise characterization of cytogenetically proven aberrations
• for the verification of aberrations that appear balanced in clinically conspicuous patients
• for characterization of genomic rearrangements
• as a complementary investigation to molecular genetic methods (e.g., further characterization of MLPA findings; validation of NGS results, if applicable)