• Tumours often show chromosome rearrangements that are not seen in normal tissues of the same person. Tumours are thought to be clonal in origin, i.e. derived from one somatic cell that accumulated a series of accidents, one of which is thought to be a chromosomal rearrangement. The tumour has an acquired rearrangement, and the sample sent to the lab for karyotyping is part of the abnormal tissue. For instance, the rearrangement could have occurred originally in one of the stem cells that produce one of the blood cell types. This is the case in the leukaemias, and the sample that you receive in the lab could be bone marrow from the flat bones (sternum, pelvis), the tissue where haemopoiesis takes place after birth. In the case of solid tumours, you will receive a biopsy from the tumour.

• Some neonates, children or adults, show at birth or develop later a constellation of dysmorphic and/or clinical features suggesting a constitutional abnormality, which can be attributed to a chromosomal abnormality present in all cells of the body. For instance, Down syndrome, or Turner syndrome. Two aspects of the phenotype that only become evident with increasing age refer to sexual function and intelligence. Unexplained mental retardation and abnormalities in sexual function including frequent spontaneous miscarriages are often causes for referral to the cytogeneticist. In all these cases, the sample sent to the lab is usually blood, the easiest tissue to provide dividing cells after in vitro stimulation with Phytohemagglutinin. Rare cases of mosaicism show abnormalities in some tissues, and not in others.

• Prenatal diagnosis may be required because certain indicators of risk, like unusual ultrasound scans or altered level of some chemicals in the maternal serum, suggest the risk of the fetus being affected by one of the constitutional abnormalities contemplated in the previous point. The tissues sampled here could be chorionic villi, amniotic fluid, or fetal blood. Chorionic villi can be sampled at around 12th week of gestation, amniotic fluid at around 16th week, and fetal blood after 18th week. Each cell type requires different culture techniques, reporting times differ, and the possibility of different types of artifact, particularly 'in-vitro' mosaicism has to be considered differently. Prenatal diagnosis of single gene disorders is also possible but this is not our concern here.

Excellent notes on the uses of cytogenetic data in these and other areas of pathology can be found in the relevant chapters of the Clinical Molecular Genetics Society (UK), which are used to prepare candiates for the MRCPath exams (slightly above the level required for your undergraduate exams). Brief summaries and some web cytogenetics references can be found by pressing the corresponding buttons above.