Our bodies function according to instructions encoded in our genetic material, deoxyribonucleic acid (DNA). This information is packaged into structures called chromosomes, located within the nucleus of almost every cell. Humans typically possess 46 chromosomes, organized into 23 pairs, each containing specific segments of DNA known as genes. Significant changes to their number or structure can alter genetic instructions, potentially leading to various genetic disorders.
What Karyotypes Show
A karyotype provides a visual representation of an individual’s entire set of chromosomes. This photographic or digital image allows scientists to examine the number, size, shape, and banding patterns of chromosomes.
The process begins with collecting cells, often from blood, bone marrow, or amniotic fluid. These cells are grown in a laboratory to encourage division. A chemical is added to halt cell division at metaphase, when chromosomes are most condensed and visible.
The chromosomes are then stained to reveal unique banding patterns, aiding identification. Finally, the stained chromosomes are photographed and arranged into homologous pairs, ordered by size and centromere position. This organized display enables the detection of chromosomal abnormalities.
Signals from Chromosome Number
Deviations from the typical count of 46 chromosomes signal genetic disorders. This abnormality, known as aneuploidy, involves either an extra or a missing chromosome. These numerical changes often arise from errors during cell division, where chromosomes fail to separate correctly.
One common example is Trisomy 21, which causes Down syndrome, characterized by an extra copy of chromosome 21. Individuals with Down syndrome have 47 chromosomes, with three copies of chromosome 21 visible on their karyotype. Similarly, Trisomy 18 (Edwards syndrome) involves an extra copy of chromosome 18, leading to 47 chromosomes. Trisomy 13 (Patau syndrome) also results from an extra chromosome 13.
Conversely, a missing chromosome can indicate a genetic disorder. Monosomy X (Turner syndrome) occurs when females have only one X chromosome instead of two. A karyotype for Turner syndrome shows 45 chromosomes, with a single X chromosome. These numerical variations are readily identifiable through karyotyping.
Signals from Chromosome Structure
Beyond numerical changes, alterations within individual chromosome structure also clue genetic disorders. These structural abnormalities involve rearrangements of genetic material within or between chromosomes. Karyotyping reveals these changes through altered banding patterns or unusual chromosome shapes.
Deletions occur when a chromosome segment is missing. For instance, Cri-du-chat syndrome results from a deletion on the short arm of chromosome 5, leading to characteristic features. Duplications involve an extra copy of a chromosome segment, meaning additional genetic material is present.
Translocations involve the exchange of segments between non-homologous chromosomes. The Philadelphia chromosome, found in most cases of chronic myeloid leukemia (CML), is a well-known example. This translocation involves a reciprocal exchange between chromosome 9 and chromosome 22, creating a shortened chromosome 22 and a longer chromosome 9. Inversions occur when a chromosome segment breaks off, flips 180 degrees, and reattaches, reversing gene order. These structural rearrangements are detectable through karyotype analysis.
Applications and Karyotyping’s Scope
Karyotyping is a tool used in several clinical scenarios. It is employed in prenatal diagnosis to screen for chromosomal abnormalities in a developing fetus, often using cells from amniocentesis or chorionic villus sampling. This technique also aids in diagnosing developmental delays, intellectual disabilities, and infertility issues by identifying underlying chromosomal causes. Karyotyping plays a role in cancer genetics, helping detect specific chromosomal rearrangements, like the Philadelphia chromosome, associated with certain cancers.
Despite its utility, karyotyping has limitations. It cannot detect small DNA changes, such as single gene mutations or very small deletions or duplications below microscopic resolution. Conventional karyotyping is limited to detecting changes larger than 5-10 megabases. This means that while it is effective for identifying large-scale chromosomal abnormalities, it will miss more subtle genetic alterations. It also requires actively dividing cells, sometimes necessitating cell culturing, which adds to the time for results.