Karyotype testing: how chromosome analysis works and what it can show

Most cells in the body contain 23 pairs of chromosomes, which carry the genes. Cambridge University Hospitals explains in its genetics information that genetic conditions can arise from a problem with the chromosomes, such as Down’s syndrome, or with individual genes, such as cystic fibrosis. A karyotype looks at the chromosomes themselves.

In a karyotype test, the laboratory examines the chromosomes down a microscope to see whether the right number is present and whether they are in the right place. The Oxford University Hospitals cytogenetics service describes the technique as G-banded analysis, in which each chromosome shows a banding pattern under the microscope. Analysis may involve the whole genome, where all chromosomes are reviewed, or targeted chromosome analysis, where only specific chromosomes are assessed, depending on the reason for referral.

Karyotyping is described by Oxford as a front-line test to detect balanced structural rearrangements, such as translocations and inversions, and to investigate sex chromosome abnormalities or mosaicism. In the NHS in England, referrals follow the National Genomic Test Directory, which lists the clinical indications for each test. Oxford’s page lists the indications for karyotyping, which give a good picture of the situations in which it is used.

For most people the test starts with a blood sample, taken in the same way as any other blood test. Cambridge University Hospitals says genetic tests usually involve a blood sample being sent to the laboratory. Oxford notes that the type of analysis, and the sample needed, depend on the reason for referral, and the genetics team will explain this to you.

In the laboratory, the cells have to be grown in culture, which is why living cells are required. Oxford notes that frozen or fixed material cannot be processed. The cultured chromosomes are then examined under the microscope. Because of the culture step, results are not instant. Cambridge says some genetic tests may be available within days, others take weeks and some several months, and that the doctor ordering the test will tell you when to expect results and how they will be given.

Oxford states that karyotyping can detect loss or gain of chromosome material and structural rearrangements, but because it is a microscope test, imbalances of about 5 Mb or greater can be detected. Smaller deletions or duplications may not be seen, and changes within a single gene are not visible.

That is where other tests come in. Oxford describes SNP microarray as a technique that examines the whole genome in greater detail than karyotyping, with a minimum resolution of about 15 kb in certain gene regions, and notes that it does not detect balanced rearrangements. Fluorescence in situ hybridisation, or FISH, uses probes to look at specific regions. Cambridge adds that microarray can sometimes identify a change that it is uncertain is causing a baby’s problems, and that blood from the parents may then help clarify this, and that rarely it finds changes that are unrelated to the problem being investigated.

In practice, a laboratory may choose a microarray for a child with developmental delay or congenital anomalies and a karyotype for a couple with recurrent miscarriage. If you are unsure why one test was chosen over another, ask the clinical genetics team.

A karyotype report describes the number of chromosomes, the sex chromosomes and any differences found, written in a standard shorthand. Cambridge says most cells contain 23 pairs of chromosomes, and a normal result reflects that. An abnormal result may show an extra or missing chromosome, a rearrangement or a mix of cell lines (mosaicism). The report does not on its own say what the finding means for health, which is why results are normally explained by a doctor or genetic counsellor.

Some findings affect family members. Oxford lists checking relatives of someone with a known rearrangement (familial cytogenetic rearrangement) among the reasons for karyotyping, so relatives may be offered testing. Cambridge notes that a sample of DNA is usually stored so that further testing can be done later without another blood test.

Charities such as Unique, which supports people with rare chromosome disorders, publish plain-English guides to chromosome changes and are named in NHS patient information.

Oxford says NHS-funded referrals should follow the National Genomic Test Directory and meet its eligibility criteria, so the test is requested by a specialist team, such as clinical genetics, rather than ordered directly by patients. A GP can discuss referral to clinical genetics or the relevant specialist if a chromosome condition is suspected.

Chromosome analysis is also available privately in some settings. Whichever route is used, it is sensible to make sure the results are reviewed by a clinician with genetics expertise and that genetic counselling is available.