A chromosome is a compact, thread-like structure found within the nucleus of nearly every cell, serving as the organized package for an organism’s DNA. These structures contain thousands of genes, which are the fundamental instructions dictating the body’s development, function, and traits. A chromosomal deletion is a mutation involving the loss of a segment of this genetic material from a chromosome. This loss can range in size from a single DNA base pair to millions of base pairs, resulting in a missing set of instructions for the cell.
How Chromosomal Deletions Occur
Most chromosomal deletions are considered de novo, meaning they arise spontaneously in the affected individual and are not inherited from the parents. The most common biological cause is an error that happens during meiosis, the specialized cell division process that creates sperm and egg cells. During this process, homologous chromosomes exchange segments of DNA in a mechanism called crossing over.
When this exchange occurs improperly, it is known as unequal crossing over or non-allelic homologous recombination. This misalignment between chromosomes can result in one chromosome losing a segment, creating a deletion, while the other chromosome gains a duplication. The severity of the resulting condition is influenced by the size of the lost segment and the number and function of the genes contained within that missing piece. Other less common causes include spontaneous breaks in the chromosome that fail to repair correctly, which can sometimes be induced by environmental factors like radiation or certain chemicals.
Different Types of Deletions
Chromosomal deletions are categorized based on their size and their physical location on the chromosome. Deletions that are too small to be seen using a standard microscope technique are called microdeletions, which typically involve the loss of only a few dozen genes or less than five million base pairs (5 Mb) of DNA. Microdeletions are significant because they often involve regions packed with important genes, leading to specific genetic syndromes. Larger deletions, which may involve a major portion of a chromosome arm, are typically detectable with conventional methods and are often associated with severe health problems.
The location of the loss further classifies the deletion into two types. A terminal deletion involves a single break near the end, or telomere, of a chromosome arm, resulting in the loss of the entire end segment. Conversely, an interstitial deletion occurs when two breaks happen within the chromosome arm, and the segment between the two breaks is lost, leaving the remaining pieces to rejoin. Interstitial deletions are often associated with more severe outcomes because the gene-rich middle sections of the chromosome arms are affected.
Health Impacts and Genetic Syndromes
The loss of genetic material from a deletion directly correlates with functional consequences, as the instructions for specific proteins or developmental pathways are missing. Health impacts often include developmental delay, intellectual disability, and congenital anomalies that affect multiple body systems. The specific symptoms depend entirely on which chromosome segment is missing and the particular genes contained within it.
One well-known example is Cri-du-chat syndrome, which is caused by a deletion on the short arm of chromosome 5 (5p-deletion). This condition is characterized by distinctive facial features, a small head, weak muscle tone, and severe intellectual disability, with the syndrome’s name referring to the high-pitched, cat-like cry observed in infants. Another common example is 22q11.2 deletion syndrome, previously known as DiGeorge syndrome, which is the most frequent microdeletion disorder. This microdeletion on chromosome 22 can lead to congenital heart defects, immune system deficiencies, palatal abnormalities, and learning differences. The loss of genes in this region impairs the development of several body systems.
Methods for Detecting Deletions
Identifying a chromosomal deletion requires different laboratory techniques depending on the size of the missing segment. For large deletions that affect several million base pairs, standard karyotyping is used. This technique involves staining and viewing the entire set of chromosomes under a microscope to visually detect major structural changes and is typically sufficient for deletions larger than 5 Mb.
When a specific, smaller deletion is suspected, such as the one causing DiGeorge syndrome, Fluorescence In Situ Hybridization (FISH) is often used. FISH employs fluorescently labeled DNA probes designed to bind only to the target region on the chromosome; if the region is missing, the fluorescent signal will be absent, confirming the deletion. For detecting microdeletions and analyzing the entire genome with higher resolution, Chromosomal Microarray Analysis (CMA), also known as array Comparative Genomic Hybridization (aCGH), is considered the gold standard. CMA allows for the detection of copy number variations, including deletions, as small as 50 to 100 kilobases.
Risk of Inheritance and Recurrence
Most chromosomal deletions occur spontaneously during the formation of the egg or sperm. In these de novo cases, the parents have normal chromosomes, and the risk of recurrence in a subsequent pregnancy is generally low, often close to the chance of the mutation happening in the general population. Genetic counseling is recommended to determine the precise individual risk.
A deletion can be inherited if one parent carries a balanced chromosomal rearrangement, such as a balanced translocation. A balanced translocation means a segment of a chromosome has swapped places with a segment from another chromosome without any net gain or loss of genetic material, so the parent is typically healthy. However, when this parent creates gametes, the chromosomes may separate incorrectly, leading to an offspring who receives a chromosome with a missing segment, resulting in an unbalanced deletion. The risk of a child being born with an unbalanced deletion in this scenario depends on the specific chromosomes involved, sometimes ranging from 1% to over 10%.