Cytogenetics & Cytogenomics

Chromosomal and genomic imbalance is assessed at the resolution the clinical question requires, from whole-chromosome analysis to submicroscopic copy-number change.

Matching resolution to the clinical question

Cytogenetic and cytogenomic methods differ chiefly in the size of the change they can see, and no single method is best for every question. Choosing correctly is largely a matter of matching resolution and scope to what is being asked.

Conventional karyotyping examines the whole chromosome complement in dividing cells. Its resolution is limited to changes of roughly five to ten megabases, but its scope is genuinely genome-wide, and it remains the method that detects balanced rearrangements — reciprocal translocations and inversions — which copy-number methods cannot see because no material is gained or lost. It also identifies structural rearrangements and marker chromosomes, and it reveals mosaicism when more than one cell line is present.

High-resolution chromosomal microarray detects submicroscopic copy-number gains and losses far below the limit of the microscope, and identifies regions of homozygosity. The trade-off is the mirror image of karyotyping: balanced rearrangements are invisible to it, because the copy number is unchanged.

Comprehensive FISH testing occupies the space between the two. It interrogates a defined locus with a targeted probe, works on interphase nuclei as well as metaphase spreads, and is therefore suited to a specific question asked of a specific region — including where dividing cells are scarce.

Cytogenomics in practice

The department’s cytogenetic work spans constitutional and acquired indications. In rare disease, chromosomal imbalance is a recurring cause of developmental and syndromic presentations, and copy-number findings are interpreted against the detailed clinical phenotype rather than in isolation — see Rare Disease Genomics. In haematological malignancy, karyotype and FISH findings contribute directly to diagnosis and risk stratification, and are read together with molecular results from Hematologic Malignancies. Prenatal and reproductive indications are described under Prenatal & Reproductive Genetics.

Automated slide scanning and imaging infrastructure supports analysis and review, and allows a preparation to be revisited without returning to the original slide.

Structural and copy-number variation is also a research theme in its own right, within the Rare Disease Genetics & Genomics programme.