From the Guidelines
Karyotyping via FISH and microarray should be chosen based on the suspected condition, with microarray being the preferred method for detecting submicroscopic chromosomal imbalances associated with developmental disorders, autism spectrum disorders, and unexplained intellectual disability, as it offers the highest resolution and can detect copy number variations across the entire genome simultaneously 1.
Key Considerations
- Traditional karyotyping examines the number and structure of chromosomes under a microscope, providing a broad overview of chromosomal abnormalities at a resolution of about 5-10 million base pairs.
- FISH is more targeted, using fluorescent probes that bind to specific DNA sequences, allowing detection of smaller abnormalities (approximately 100,000-200,000 base pairs) that karyotyping might miss.
- Microarray analysis offers the highest resolution (about 25,000-50,000 base pairs) and can detect copy number variations across the entire genome simultaneously.
Choosing the Right Technique
- The choice between these techniques depends on the suspected condition, with karyotyping often used as a first-line test, while FISH targets known genetic regions, and microarray provides comprehensive genome-wide analysis for unexplained conditions 1.
- Microarray is especially valuable for identifying submicroscopic chromosomal imbalances associated with developmental disorders, autism spectrum disorders, and unexplained intellectual disability 1.
Important Considerations for FISH and Microarray
- FISH should be used to confirm or visualize abnormal findings identified by copy number microarrays, and the molecular identity of the FISH probe should be verified, as well as the identity of the clone on the array 1.
- Occasionally, FISH and microarray results may be discordant, and the quality of the array and FISH data should be reviewed, and testing repeated, if warranted 1.
- The laboratory director must ensure that confirmation can be established and, if confirmation is to be performed by FISH, that clones are available to the laboratory in a timely manner to maintain clinically relevant turnaround times 1.
From the Research
Karyotyping via FISH and Microarray
- Karyotyping is a process that involves the analysis of the number and structure of chromosomes in an individual's cells.
- Fluorescence in situ hybridization (FISH) and microarray are two techniques used for karyotyping.
- FISH is a molecular cytogenetic technique that uses fluorescent probes to detect specific DNA sequences on chromosomes 2.
- Microarray, on the other hand, is a high-throughput technique that allows for the analysis of multiple genomic regions simultaneously 3, 4.
Diagnostic Utility of Microarray
- Microarray has been shown to be a valuable tool in the diagnosis of genetic disorders, including developmental delay, intellectual disability, and autism spectrum disorder 3, 4, 5, 6.
- Studies have demonstrated that microarray can detect copy number variations (CNVs) that are associated with these disorders, with detection rates ranging from 16.9% to 28.1% 3, 4, 6.
- The use of microarray as a first-tier diagnostic test has been recommended by several professional organizations, including the American College of Medical Genetics 5.
Comparison of FISH and Microarray
- FISH is a targeted technique that is used to detect specific genetic abnormalities, whereas microarray is a genome-wide technique that can detect CNVs across the entire genome 2, 3.
- Microarray has been shown to be more sensitive than FISH in detecting CNVs, particularly in cases where the abnormality is small or complex 3, 4.
- However, FISH is still a useful technique in certain situations, such as when a specific genetic abnormality is suspected or when microarray results need to be confirmed 2.