Chromosomal testing and genomic sequencing concepts

Synopsis

Choose genomic tests by the biological question, explain resolution and blind spots, interpret copy-number and sequence findings with phenotype, and prepare families for uncertain, secondary and familial implications.

• Start with phenotype and the current NHS indication: eligible syndromic or moderate-to-profound developmental disorders usually enter R27 whole-genome sequencing, while R28 microarray is reserved for a recognisable chromosomal cause.
• Karyotyping visualises chromosome number and large structural rearrangements, including balanced changes that many copy-number assays cannot define.
• Chromosomal microarray detects submicroscopic genomic gains and losses across the genome but usually does not identify balanced translocations or single-nucleotide variants.
• Targeted tests answer focused questions: rapid aneuploidy assays, FISH, MLPA, repeat-primed PCR and methylation studies each detect selected mechanisms rather than all genetic disease.
• Panel, exome and genome sequencing compare DNA sequence across progressively broader territory, but coverage, variant types and analysis scope remain test- and laboratory-specific.
• A pathogenic result should fit inheritance and phenotype; a variant of uncertain significance is not a diagnosis and should not drive irreversible management by itself.
• A negative result can mean no causal change was found by that method, not that the condition is non-genetic or recurrence risk is zero.
• Obtain valid consent that covers expected outcomes, uncertainty, possible findings relevant to relatives, data handling and whether future reinterpretation or recontact may occur.