A standard chromosome test, called a karyotype, involves photographing chromosomes under a microscope and lining them up by size and shape. A trained analyst can spot a piece of chromosome that is unusually large, unusually small, or attached to the wrong chromosome, but only if that piece is big enough to see, generally above five to ten million building blocks of DNA. A chromosomal microarray works completely differently. Instead of a picture, it uses thousands to millions of tiny probes fixed to a small chip, each one designed to bind to a specific, known stretch of the genome. A sample of the person’s DNA is processed, labeled, and washed over the chip, and a scanner measures how strongly each probe’s genetic material binds. Where a stretch of chromosome is missing, the signal is fainter than expected; where a stretch is duplicated, the signal is stronger than expected. A computer then compares this pattern across the entire genome against a reference, flagging every region that looks gained or lost.

This approach can reliably detect imbalances as small as fifty to one hundred thousand building blocks, roughly fifty to one hundred times smaller than what a karyotype can see, which is why it identifies genetic causes that older testing missed for decades. There are two main types of chip in use. An array using comparative genomic hybridization measures gains and losses only. A single nucleotide polymorphism array does the same, but additionally reads out common genetic variation at each point, which lets the laboratory detect situations where a person has inherited two copies of a chromosome region from one parent and none from the other, called uniparental disomy, and can help identify parental relatedness or a mixture of genetically different cells in one person, called mosaicism.

What a chromosomal microarray cannot do is just as important to understand. Because it only measures the amount of genetic material present, it cannot see a rearrangement where chromosome pieces have simply swapped places without any material being gained or lost, and it cannot detect a change within a single gene, such as a single altered letter of the genetic code. Those situations need a different kind of test, one that reads the genetic code itself, such as exome or genome sequencing, discussed further below.