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Clinical cytogenetics is the study of chromosomes and the way that changes to their number and structure can lead to disease or disability.

The normal human has 46 chromosomes, 23 pairs: 22 autosomes (1-22) and the sex chromosomes, XX for female, XY for male.

A clinical cytogeneticist loks at the 23 pairs of chromosomes in an individual looking for losses, gains or rearrangements of the genetic material. This technique is called karyotyping. Traditionally this is done with stains that differentiate between areas that are gene-rich and those that are gene-poor. The stained, or banded, chromosomes are viewed used light microscopy – which has a minimum resolution of 5-10 Mega bases (Mb). A point of reference is that chromosome 21, where 3 copeis are seen in Down syndrome, is about 35-40Mb in length.

We can increase our resolution by asking specific questions with long strands of DNA which are attached to flurescent probes. This technique is called fluorescent in situ hybridiation (FISH) and can be used to look for single gene deletions. FISH is NOT a whole genome scan like karyotyping as the FISH probes are specific to particular streches of DNA within the genome.

A relatively new technique in cytogenetics is array comparative genome hybridisation (aCGH). In short, aCGH compares the patients genome with a normal control. This is a whole genome screen and at the end a “virtual” karyotype is examined. This technique provides so much data that it would be nearly impossible for a human to understand it and we need a superfast computer to process the results.

In the not too distant future though, I think that this kind of microscope work will be replaced by Star Trek-like scanners and the microscope will only be seen in the museum. If you want to see what I am talking about – just google New Generation Sequencing, or better still Quantum DX, a pocket-sized genome scanner.

Cancer cytogenetics is heavily dependent on the FISH I mention above. This looks for fusions between genes which should have been brought together. This reults in genes being turned on when they shouldn’t be and can lead to cancer.

I spend time looks for abnormal results for FISH. I also look at karyotypes to see if there is anything that FISH has missed or couldn’t detect.

What I really like is being able to give patients good news, telling them that “Ok, you have cancer but our work shows that you can be cured by this treatment”. Obviously there are bad days too when we have to give really bad news.