Scientists have described the average human genome

The genome of each person contains about 5 million variants — DNA segments that differ between individuals. Of these, about 10,000 change the gene sequence itself; the impact of such variants can be both beneficial and harmful — ranging from lactose intolerance to differences in drug response, but most often they are biologically neutral.

Moreover, each person has between one and three rare variants that have previously been proven to cause serious hereditary diseases, and about 50 more rare variants whose clinical significance is still unclear.

The authors also calculated polygenic risks — estimates that take into account all known genetic factors to calculate the likelihood of developing a disease in the future. After analyzing polygenic scores for 28 common conditions, including diabetes, cardiovascular diseases, and schizophrenia, they found that most people fall into the high genetic risk category for about three diseases.

However, the researchers did not check the participants’ health status, so many of these people may not have any of the listed diseases. The result suggests that such findings may be part of normal genetic variation, and other factors also play a decisive role in the development of the disease.

“Whole‑genome sequencing has become a crucial tool for diagnosing genetic diseases, and we are increasingly moving towards genetic screening to predict diseases,” says Professor Caroline Wright from the University of Exeter. “But most people don’t realize how much genetic variation is contained in each genome. In fact, variation is the norm.” For the first time, our study describes what to expect from the average human genome, which will help clinicians and patients around the world understand, interpret, and contextualize genomic data.

According to her, the key practical conclusion is that everyone carries a small number of variants associated with diseases, but many of them will not cause disease in a given individual. Therefore, when interpreting the results of genetic testing, context is critically important: symptoms, family history of diseases, and other clinical and environmental risk factors.

The study also includes findings relevant to reproductive medicine. Among participants in biobanks who were selected together with their parents, scientists found an average of 63 new variants that neither the father nor the mother had. Such mutations are called de novo: most of them arose in the father’s sperm, and some in the mother’s eggs. Their number increases noticeably with the father’s age — by approximately 1.2 mutations per year — and this is important to take into account when planning a family.