In the nucleus of every human cell, thread-like structures called chromosomes house our complete genetic instruction set, DNA. Humans have 23 pairs of chromosomes, with one set inherited from each parent. Alterations to these structures can occur, potentially affecting an individual’s development and health.
Understanding Chromosomal Alterations
Chromosomal alterations are changes to chromosome structure or number. These alterations fall into two main categories: numerical and structural. Numerical alterations involve an atypical number of chromosomes.
A common type is aneuploidy, where there is an extra or missing chromosome. Trisomy, for instance, means there are three copies of a particular chromosome instead of the usual two, such as in Down syndrome (Trisomy 21). Conversely, monosomy refers to the absence of one chromosome from a pair, like in Turner syndrome (Monosomy X). Polyploidy involves the addition or loss of entire sets of chromosomes.
Structural alterations involve rearrangements within one or more individual chromosomes. These changes result from breaks and improper rejoining of segments. Examples include:
Deletions, where a segment of a chromosome is lost.
Duplications, where a segment is present more than once.
Inversions, where a chromosomal segment breaks off, flips 180 degrees, and reattaches, reversing the gene order.
Translocations, which involve the transfer of a segment from one chromosome to another, which can be reciprocal or Robertsonian.
How Chromosomal Alterations Arise
Chromosomal alterations primarily arise from errors during cell division, meiosis and mitosis. Meiosis creates sperm and egg cells, while mitosis is involved in the division of somatic (body) cells. A common error is non-disjunction, the failure of homologous chromosomes or sister chromatids to separate properly.
Non-disjunction can occur during meiosis I or meiosis II, when chromosomes fail to separate. If a gamete with an abnormal number of chromosomes is fertilized, the resulting zygote will have an altered chromosome count. Mitotic non-disjunction can lead to mosaicism, where an individual has a mix of cells with different chromosomal compositions. Beyond errors in cell division, external factors like certain chemicals and radiation can induce structural changes or genomic instability in chromosomes.
Health Impacts of Chromosomal Alterations
Chromosomal alterations can lead to a wide range of health and developmental consequences. These changes can result in outcomes from mild developmental delays to significant congenital anomalies or intellectual disabilities. Many recognized genetic syndromes are directly linked to these alterations, affecting various body systems.
For example, Down syndrome (Trisomy 21) is associated with developmental delays, mild to moderate intellectual disability, and characteristic physical features. Individuals with Down syndrome also have an increased risk of congenital heart defects, epilepsy, and thyroid diseases. Edwards syndrome (Trisomy 18) involves severe developmental delays, multiple birth defects, and poor growth before and after birth, often with life-threatening complications. Klinefelter syndrome (47, XXY) can lead to infertility, smaller testes, and potential delays in motor and cognitive development.
Identifying Chromosomal Alterations
Several methods are employed to detect chromosomal alterations. Karyotyping is a widely used technique that involves examining chromosomes under a microscope to assess their number and structure. Cells are stained to create distinct banding patterns, allowing identification of individual chromosomes and large-scale abnormalities. Karyotyping is used for prenatal diagnosis or in children with unexplained developmental issues.
Fluorescence In Situ Hybridization (FISH) offers a more targeted approach, using fluorescent probes that bind to specific DNA sequences on chromosomes. This technique can detect smaller deletions, duplications, or rearrangements that might be too small to be seen with standard karyotyping. Chromosomal microarray analysis (CMA) provides the highest resolution, detecting very small gains or losses of genetic material across the entire genome. CMA is useful for identifying submicroscopic imbalances associated with developmental delays, intellectual disabilities, and autism spectrum disorders.
Inheritance and Family Considerations
Chromosomal alterations can either occur spontaneously or be inherited from a parent. Many numerical alterations, such as those caused by non-disjunction, are spontaneous errors during the formation of egg or sperm cells or in early embryonic development. However, some structural alterations, like balanced translocations, can be inherited. In a balanced translocation, a person has the correct amount of genetic material, but it is rearranged without causing health problems for the carrier.
Despite being healthy, carriers of balanced translocations have an increased risk of producing offspring with an unbalanced alteration. This can lead to recurrent miscarriages, infertility, or the birth of a child with congenital anomalies or developmental issues. Genetic counseling is important for families facing these considerations, as counselors can explain the specific alteration, discuss the likelihood of recurrence in future pregnancies, and explore reproductive options, including prenatal diagnosis or preimplantation genetic diagnosis.