Expansion
Resolution rises from whole chromosome to single base
Expansion
| Test | Resolution | Detects | Misses |
|---|---|---|---|
| Karyotype | Whole chromosome | Aneuploidy (trisomy 21), large deletions, translocations, mosaicism | Anything under about 5 Mb |
| FISH | Targeted locus | Known microdeletions (22q11), rapid aneuploidy, gene rearrangements | Anything not specifically probed |
| Microarray (CGH) | 50 to 100 kb | Copy number variants, microdeletions and duplications genome wide | Balanced translocations, point mutations |
| Sanger sequencing | Single base | Point mutations in one gene | Large deletions, other genes |
| Gene panel | Single base | Mutations across a defined set of genes | Genes outside the panel |
| Whole exome | Single base | Coding variants genome wide, about 2 per cent of the genome | Non-coding, repeats, copy number |
| Whole genome | Single base | Almost everything, including structural variants | Some repeats |
The two blind spots that matter clinically
- Balanced translocations are invisible to microarray, because no genetic material is gained or lost. A karyotype is needed, which is why recurrent miscarriage is investigated with karyotyping of both parents
- Copy number variants and trinucleotide repeat expansions (Huntington’s, fragile X, myotonic dystrophy) need specific methods, and are missed by standard sequencing
Consent and counselling matter more than for other tests, because results affect family members, may be unwanted, can affect insurance, and often return variants of uncertain significance, which are common and frequently more distressing than a clear result.
Predictive testing for adult onset conditions is usually deferred in children until they can consent, unless childhood intervention would change the outcome.