What Is Comparative Genomic Hybridization (CGH)?
Array-based Comparative Genomic Hybridization (CGH) is a new method for detecting chromosomal abnormalities. Traditionally, in high-risk pregnancies (for specific genetic diseases or common chromosomal abnormalities such as trisomy 21, 18, 13), amniotic fluid or chorionic villus sampling (CVS) is analyzed by conventional chromosome testing. This method can only diagnose a limited number of disorders. However, it is now known that more than 70 conditions associated with birth defects or developmental disorders are caused by deletions or duplications of small chromosomal segments. These can be identified using microarray-based CGH, which evaluates copy number variations across thousands of genomic regions simultaneously.
ACOG Guidelines on Prenatal Array CGH (November 2009)
Conventional karyotype analysis remains the standard cytogenetic method for prenatal diagnosis. Array CGH may be offered—together with genetic counseling—in cases where there are abnormal anatomical findings with a normal karyotype, when karyotype analysis cannot be obtained, or in intrauterine fetal death associated with congenital anomalies. Couples should be informed that array CGH cannot detect all genetic abnormalities. While it can be a useful screening tool, further studies are needed to fully define its indications and limitations.
Features of Comparative Genomic Hybridization (CGH)
On the microarray chip, DNA fragments representing specific regions of the human genome are present. The patient’s DNA is hybridized to the chip, allowing detection of unbalanced chromosomal abnormalities (copy number variations) that cannot be identified by conventional karyotyping.
Karyotype Analysis or CGH?
Since the 1970s, karyotype analysis has been the gold standard for prenatal cytogenetic diagnosis. Conventional karyotyping can detect microscopically visible aneuploidies, balanced/unbalanced chromosomal translocations, inversions, and mosaicism, but typically cannot detect chromosomal changes smaller than 4–5 Mb. Karyotype analysis also requires cell culture and usually takes 10–14 days for results. Importantly, it cannot detect submicroscopic deletions, duplications, or other rearrangements—structural genomic changes that are associated with up to 17% of syndromic or non-syndromic intellectual disability.
By contrast, microarray-based CGH provides faster results and can detect small (submicroscopic) gains and losses, as well as unbalanced rearrangements (DNA loss or gain). However, it cannot detect balanced translocations, inversions, point mutations, or copy number changes not represented on the array. Currently, microarray CGH is widely used in pediatrics for diagnosing cytogenetic and genomic disorders associated with intellectual disability, autism, dysmorphism, and developmental delay. Its role in prenatal diagnosis continues to be evaluated.
Beyond prenatal diagnosis, CGH is also being used to investigate the genetic causes of spontaneous miscarriages and intrauterine fetal demise. Research in this field is ongoing.
Sampling
Like karyotype or FISH testing, CGH requires an invasive sampling procedure such as chorionic villus sampling or amniotic fluid collection. In one study, microarray CGH was successfully performed using DNA from just 1 ml of amniotic fluid—much less material than is typically required for karyotyping.
Who Is CGH Recommended For?
- Pregnancies with abnormal fetal ultrasound findings
- Cases with uncertain results from chromosome analysis
- Suspected deletion/duplication syndromes
- Intrauterine fetal death or spontaneous miscarriage
- Recurrent pregnancy loss
- Pregnancies with a family history or suspected chromosomal disorder
