Errors and variations found in the genomes of individual human cells

Mutations in the human genome occur more often than previously expected, but are not deemed harmful, according to a new study.

Each cell in the adult human body, that contains a nucleus, has its own copy of the genome. When a cell divides, it makes an exact copy of its DNA. Although this process is known not to be perfect, cells have mechanisms in place that generally enable mistakes during this process to be detected and repaired. The mutations that sometimes arise despite these protective mechanisms can increase the risk of diseases, such as cancer, developing. Now, scientists in Germany have studied blood stem cells from 19 healthy people of different age and discovered that one in 43 individual cells carried major chromosomal alterations in their DNA. Furthermore, people older than 60, carried even higher levels of cells with abnormal DNA, which the researchers suggest might contribute to age-related diseases.

Dr Ashley Sanders from the Max Delbrück Centre for Molecular Medicine, Berlin, Germany, and co-lead author of the study published in Nature Genetics, said: 'We are just recognising that contrary to what we learned in textbooks, every cell in our body doesn't have the exact same DNA. It's just amazing how much heterogeneity there is in our genomes that has gone undetected so far. What this means in terms of how we define normal human ageing and how this can impact the types of diseases we get is really an important question for the field.'

Using a single-cell sequencing technique that is able to detect subtle genomic changes in single cells, the researchers sequenced 1133 single-cell genomes from 19 people ranging from newborn to 92 years.

Specifically, the researchers looked for mosaic structural variants within each individual blood stem cell, which are structural changes that occur in the DNA of a single cell. They then looked at the effects of the chromosomal changes on cellular function.

The researchers found that 16 of the 19 people in this study carried mutations within their single-cell genomes – termed mosaicism – which refers to cells in an individual with a different genetic makeup. The researchers suggest that large genetic alterations are common in blood stem cells of healthy people.

Mosaic structural variants are continuously acquired throughout life, these clonal variants can expand to form subclones, which are synonymous with the development of cancer, and other age-related diseases. In this study, expanded subclones were only found in people over the age of 60, with certain genetic variant subclones occurring more often than others, suggesting their presence could be connected with the development of age-related diseases. However, the researchers note that it is not clear whether the subclones are a cause or the result of the ageing process.

Dr Jan Korbel from the Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany, and co-lead author of the study, said: 'The study highlights that we are all mosaics. Even so-called normal cells carry all sorts of genetic mutations. Ultimately, this means that there are more genetic differences between individual cells in our bodies than between different human beings. In the future, our single-cell studies should give us clearer insights into how these mutations that previously went unnoticed affect our health and potentially contribute to how we age.'