Genetic diagnostic technology is rapidly improving. DNA or RNA can be amplified, producing many copies of a gene or gene segment, using PCR.
Gene probes can be used to locate specific segments of normal or mutated DNA. Different types of probes may investigate a broad range of sizes of DNA sequence. A known DNA segment may be cloned and then fluorescently tagged (using fluorescent in situ hybridization [FISH]); this segment is then combined with a test specimen. The tagged DNA binds to its complementary DNA segment and can be detected by measuring the amount and type of fluorescence. Gene probes can detect a number of disorders before and after birth.
Oligonucleotide arrays (probes) are another type of probe now routinely utilized to identify deleted or duplicated regions of DNA sequence in specific chromosomes on a genomewide basis. DNA from a patient is compared to a reference genome using many oligonucleotide probes. Using such probes, the entire genome can be tested (queried).
Microchips are powerful new tools that can be used to identify DNA mutations, pieces of RNA, or proteins. A single chip can test for millions of different DNA changes using only one sample. Microchips provide finer resolution for genome queries than oligonucleotide arrays.
Next-generation sequencing technologies provide the highest degree of resolution but have many still-unsolved analytical and computational challenges (eg, how to interpret results, particularly for complex, multigenic disorders). Next-generation sequencing involves breaking the entire genome into small segments and then doing base by base sequence analysis on some or all of the segments depending on whether a subset of genes or the genome is the target of interest. The segment results are analyzed (using intensive computational power) to provide a composite result of the sum of all the mapped small segments. Single nucleotide variants may be identified as well as very short segments that have been inserted or deleted. Some of these variants can be diagnostic for genetic disorders.
Last full review/revision July 2013 by David N. Finegold, MD
Content last modified October 2013