Researchers have discovered that around 1 in 40 human bone marrow cells have significant chromosomal changes without showing any signs of illness or abnormalities. This means that even cells that are considered “normal” can have various genetic mutations, resulting in more genetic variations between individual cells in our bodies than between different human beings. This breakthrough was made possible by a specialized DNA sequencing technique called Strand-seq, which allows researchers to uncover intricate details of genomes in single cells that would be difficult to detect using other methods. This study was led by Jan Korbel at the Eu.Researchers at the European Molecular Biology Laboratory (EMBL) and the Berlin Institute for Medical Systems Biology of the Max Delbrück Center (MDC-BIMSB) have discovered that around 1 in 40 human bone marrow cells contain significant chromosomal changes, such as copy number variations and chromosomal rearrangements, without causing any observable disease or abnormality. Furthermore, cell samples from individuals over 60 years old appeared to have more cells with these genomic alterations, indicating a previously unknown mechanism that could potentially lead to age-related diseases. The findings were published in a scientific journal.The journal Nature Genetics.
“The research emphasizes that we are all mosaics,” stated Korbel, who is a Senior Scientist in the Genome Biology Unit and leads the Data Science team at EMBL Heidelberg. “Even what are considered normal cells contain various genetic mutations. Ultimately, this means that there are more genetic variations among individual cells in our bodies than between different individuals.”
Both Korbel and Sanders, who is a Group Leader at the Max Delbrück Center, explore the effects of genetic structural variation — such as deletions, duplications, inversions, and translocations of large sections of the human genome — on human health.The advancement of disease can be attributed to genetic mutations causing uncontrolled cell growth and tumor formation. This concept, well-known in the cancer field, is now being applied to understand the development of non-cancerous diseases. Sanders explained that the discovery was made possible by the use of a single-cell sequencing technology called Strand-seq. This unique DNA sequencing technique can uncover intricate details of genomes in single cells that are difficult to detect through other methods. Sanders played a key role in the development of this technology during her doctoral research.Protocol, which she later refined with colleagues while working as a postdoctoral fellow in Korbel’s lab. Strand-seq allows researchers to identify structural variations in individual cells with greater precision and resolution than any other sequencing technology, according to Sanders. The technology has brought about a completely new understanding of genetic mutations and is now widely used to analyze genomes and translate findings into clinical research. “We are just realizing that, contrary to what we learned in textbooks, every cell in our body doesn’t have the exact same DNA,” she said. Genetic mosaic.The research is the first to use Strand-seq technology to study DNA mutations in healthy individuals. Biological samples from various age groups were examined, and mutations were found in the blood stem cells of 84% of participants, ranging from newborns to 92-year-olds. This indicates that significant genetic mutations are widespread. “It’s astonishing how much diversity exists in our genomes that has gone unnoticed,” Sanders noted. This discovery has implications for our understanding of normal human aging and genomic variability.The impact of these findings on the types of diseases we may develop is a crucial question for the field. The study also discovered that in individuals aged 60 and above, bone marrow cells with genetic mutations were more prevalent, with certain genetic variations or sub-clones being more common than others. The frequent presence of these sub-clones suggests a potential link to the aging process. However, it is still not clear whether the mechanisms that control the proliferation of sub-clones weaken as we age, or if the expansion of sub-clones itself contributes to age-related diseases, according to Korbel. He also mentioned that in the future, single cell technology may help provide more insights into this topic.The research should provide us with a better understanding of how these previously unnoticed mutations impact our health and may contribute to the aging process.”
