A groundbreaking study conducted by researchers from the Center for Genomic Regulation (CRG) in Spain and Harvard Medical School, published in the peer-reviewed journal Nature Communications, has identified a critical “weak spot” in human DNA that is particularly prone to errors during embryonic development.
The research team discovered that an area known as Transcription Start Sites (TSS)—located within the first 100 base pairs following gene initiation—is especially vulnerable to mutations.
This discovery opens new doors to understanding the origins of numerous diseases, ranging from cancer to developmental disorders.
What Are Mosaic Mutations?
The authors found that these “mosaic mutations” typically occur after fertilization, during the earliest stages of cell division in the embryo.
A mosaic mutation refers to the presence of two or more groups of cells with different genetic compositions within an individual who developed from a single fertilized egg (zygote).
Rather than being inherited from parents, this genetic variation arises from errors that occur during cell divisions in embryonic development (post-fertilization). As a result, not all cells in the body carry this mutation—only a specific portion does. This causes the individual’s cellular structure to display genetic diversity resembling a “mosaic” composed of different colored tiles.
The Hidden Danger
A person carrying these mutations may never realize their condition due to the absence of symptoms. However, the situation becomes serious if these genetic changes are passed on to their children.
When the mutation is transmitted to offspring, it is present in all of the child’s cells and can lead to various health problems including cancer, brain function disorders, or limb development abnormalities.
Scientists utilized a massive data pool to uncover this hidden vulnerability. Using data from the Genome Aggregation Database and the UK Biobank, approximately 225,000 TSS regions were examined.
A New Era in Genetic Modeling
Beyond facilitating the study of difficult-to-detect mosaic mutations, this research will also refine the mutation models used by scientists.
Current models can produce misleading results because they assume the “natural” mutation rate in TSS regions is very low.
