The genetic information in our cells guides the development and function of our bodies. Typically, all cells within an individual share an identical genetic makeup. However, mosaicism is an exception, involving different genetic compositions within the cells of a single individual. Understanding mosaicism provides insights into the complexities of human biology.
Defining Genetic Mosaicism
Genetic mosaicism describes a condition where an individual possesses two or more distinct populations of cells, each with a different genetic composition, yet all originating from a single fertilized egg. This contrasts with the typical scenario where all cells in an organism are genetically identical.
The differing genetic compositions can range from changes in a single DNA base pair to alterations in entire chromosomes. While most cells in a person share the same DNA, mosaicism means some cells carry a variation or change. The presence of these distinct cell populations, all derived from the same initial fertilized egg, is the defining characteristic of mosaicism.
How Mosaicism Develops
Mosaicism primarily arises from errors that occur during cell division after fertilization, a process known as post-zygotic mutation. As a fertilized egg undergoes countless divisions to form a complete organism, each cell division presents an opportunity for genetic mistakes. These errors can lead to new genetic changes in a subset of cells, which are then passed on to all subsequent cells derived from that mutated cell.
One common mechanism is mitotic non-disjunction, where chromosomes fail to separate properly during mitosis. This error can result in daughter cells having an incorrect number of chromosomes, such as an extra chromosome (trisomy) or a missing chromosome (monosomy). Another mechanism is anaphase lag, where a chromosome or chromatid fails to be incorporated into either of the new daughter nuclei after cell division, leading to its loss in one cell line. Additionally, a gene mutation can occur in a single cell during early development, and this new mutation will then be replicated in all the cells that descend from that original mutated cell.
Types of Mosaicism
Genetic mosaicism manifests in different forms, primarily categorized by the type of cells affected. The most common distinctions are somatic mosaicism and germline mosaicism. These classifications determine whether the genetic change affects the individual’s body or can be passed on.
Somatic mosaicism involves genetic changes in non-reproductive body cells, such as those found in skin, brain, or blood. The effects are typically localized to the tissues or organs where altered cells are present. For instance, a genetic change in skin cells might lead to a skin condition, but it cannot be passed on to offspring.
In contrast, germline mosaicism, also known as gonadal mosaicism, occurs specifically in reproductive cells (sperm or eggs). An individual with germline mosaicism may not exhibit symptoms themselves, as their somatic cells are unaffected. However, they can pass the genetic condition to their children, even if the mutation is not detectable in their own non-reproductive cells. It is also possible for an individual to have both somatic and germline mosaicism.
Detecting Mosaicism and Its Importance
Detecting mosaicism can be challenging because it involves identifying small populations of genetically distinct cells within a larger group of normal cells. Specialized genetic testing methods are often necessary to uncover these variations. Techniques such as Next-Generation Sequencing (NGS) with high depth, single-cell sequencing, quantitative PCR, and Fluorescence In Situ Hybridization (FISH) are increasingly used.
The importance of recognizing mosaicism is particularly in its implications for human health and genetic counseling. The presence, proportion, and location of affected cells can lead to a wide spectrum of outcomes, from severe symptoms to mild manifestations, or even no apparent symptoms at all. This variable presentation makes diagnosis difficult, as standard genetic tests might miss mosaicism if the affected cells are not present in the tested tissue or are in very low proportions. For genetic counseling, understanding mosaicism is crucial for accurately assessing recurrence risk in families, especially when germline mosaicism is suspected in a parent who has an affected child but does not show symptoms themselves. Mosaicism is increasingly recognized as a factor in various conditions, ranging from developmental disorders to cancer, highlighting its broad impact on human health.