Molecular karyotype (a-CGH) – high resolution

Chromosomal abnormalities have been identified as the main cause of developmental delay, mental retardation, autistic spectrum disorders as well as multiple congenital abnormalities. Until recently, the only available method of detecting chromosomal abnormalities was conventional G-banding karyotype, which screens all chromosomes for aneuploidy and segmental lesions up to the limit of 5-10 Mb.

Chromosomal microarray analysis with molecular karyotype (aCGH) is a new method that enables the detection of chromosomal abnormalities that are accompanied by a change in the copy number of genetic loci (aneuploidy, deletions, duplications) across the entire genome of a patient, with an effective resolution of up to 50Kb.

Numerous studies have shown the benefits of applying molecular karyotype to patients with developmental delay and multiple congenital abnormalities of unknown etiology, leading to the establishment of molecular karyotype as the first tier test for these patients. In particular, it has been reported that molecular karyotype offers a diagnostic yield of 15-20% compared to about 3% for conventional karyotype. The important advantages of the method include the ability to detect any quantitative change across the entire genome of a patient with an average resolution that is about 1,000 times higher than that of the conventional karyotype, resulting in the detection of cryptic microdeletions and microduplications known to be responsible for a large number of genetic syndromes.

Chromosomal microarray analysis with molecular karyotype is recommended in: • patients with developmental delay / mental retardation and congenital anomalies of unknown cause, especially when conventional karyotypic analysis is negative or reveals a balanced translocation as well as • patients with autistic spectrum disorders and normal conventional karyotype

Our laboratory utilizes the integrated microarray system of Agilent Technologies, one of the most sophisticated platforms available at the moment. The 4x180K CGH + SNP high resolution 4x180K microarrays provide a resolution of 50kb on average, and even greater in regions of the genome with important genes (gene-oriented arrangement), while 99% of known genes are covered by at least 3 probes. At the same time, SNP probes allow the detection of regions with Loss of Heterozygosity (CN-LOH).

 

Method: Comparative genomic hybridization to Agilent’s G3 4x180K CGH + SNP microarrays, that cover the entire genome with ~ 180,000 oligonucleotide probes with higher density in regions with genes that have been associated with genetic disorders, providing an average resolution of 50kb. SNP probes enable the simultaneous detection of regions with Loss of Heterozygosity (CN-LOH).

Sample type: 2ml blood sample in EDTA containing tube

Time to result: 4 weeks

aCGH+SNP is not able to detect point mutations, balanced translocations and low level mosaicism.