What is a genome and why is mapping it so valuable? An expert explains

This article was first published in April 2023. It was updated in May 2023 and again in September 2023.

Just weeks after the Human Genome Project celebrated its 20th anniversary, a new milestone in DNA mapping was reached that promises to make medical research more equitable.

As the World Economic Forum's Global Health and Healthcare Strategic Outlook pointed out, "discrepancies in health equity are entrenched in healthcare data" which currently relies on "limited diversity".

In an attempt to more accurately represent all of human genetic variation, scientists have created a draft "pangenome", which sequences DNA from 47 people from Africa, the Americas, Asia and Europe and could help research into the links between genes and disease.

The Human Pangenome Reference Consortium, which was launched in 2019 and published its research in the scientific journal Nature, builds on the work of the Human Genome Project. It sequenced the human genome, almost in its entirety, for the first time in April 2003 – but was mostly based on the DNA of one person.

The Human Genome Project took 13 years and was a global collaborative effort that cost around $3 billion and involved researchers from 20 universities and research centres from the US, UK, France, Germany, Japan and China. Together these groups became known as the International Human Genome Sequencing Consortium.

A genome – the "book of life" – is the entire set of genetic information about a person or organism. Mapping an individual’s DNA can help scientists to study gene mutations that cause diseases, including cancer, and could allow doctors to prescribe personalized precision medicine in future.

The human Y chromosome, which determines the male sex among other functions, has recently had its sequence completed – this is "the final piece of the human pangenome," reports Nature, and could eventually lead to breakthroughs in infertility treatments.

Magdalena Skipper is a geneticist and Editor-in-Chief of Nature, which published the draft human genome sequence in 2001.

Here, she explains what the original project has taught us about ourselves and how it’s developed our understanding of genetics over the past two decades.

The simplest way to explain it is to think of it as a set of instructions to build a certain biological entity. These instructions are open to interpretation, which means a genome doesn't exist in a vacuum – it exists in the context of the environment. Let’s compare it to different people reading a poem. A poem is written in a certain way, made up of letters and words. But if you get different people reading that poem, it may provoke different emotions and may have different dynamics.

In my analogy, the different people reading it will be the different environmental conditions in which that poem of the genome is read out. The genome is a set of instructions, and of course, it is made up of genes. But there is so much more to a genome beyond the genes. There are instructions on how to read those genes and many other elements which, incidentally, we are continuing to explore and understand their full meaning and full functionality.

The sequencing of the human genome took place some 20 years ago now, and this really was a collaborative international effort. Today, sequencing of genomes has become much simpler. It's now applied in the context of the clinic, in the context of understanding the complexity of the human population, in the context of understanding our history.

So genomics mixed with the medical profession, palaeontology, archaeology, gives us insights into those other disciplines which we could never really arrive at without that particular contribution. It's not just information about disease susceptibility or the nature of diseases, but it's also information about the most effective treatment that an individual or a specific population is most likely to respond to well, or indeed not have any adverse effects.

We intuitively understand aspects of genetics. We all have relatives, parents, perhaps children, siblings. We know we are similar to members of our family and different from others and of course, the reason for it lies in our genes, the fact that we share our genetic information with our family members. And yet it's a discipline that is often misunderstood, for example, under the guise of genetic determinism.

It's been fascinating to watch how, with the availability of the human genome and this genomic information for other organisms, we have begun to chart the map that defines us as a biological entity and other biological entities around us. It's fascinating that more than two decades since the first human genome sequence, we have learned an enormous amount about ourselves and that "book of life", as it's sometimes referred to.

The more we learn from it, the more we realize that the issue is extremely complex. Our genetics unfolds in the context of the environment, and it's that interaction between our genetics and our environment which is incredibly complex. For example, whether we develop certain diseases, let's say certain types of cancer, is indeed a combination of our genetics, but also our environmental exposures, our habits, what we eat, how we behave, what we drink and what perhaps hazardous materials we come across.

Today we think about genome engineering, although in the context of medicine, it's still a future prospect rather than a current reality. So much of today's medicine has already been influenced by our understanding of genetics and genomics, in terms of susceptibility to disease and medication. Depending on one's genetic background, different drugs may be prescribed for a specific ailment over a different period of time. We also understand so much more about how genetics mixes with our genetic ancestry. So we know that certain drugs work in some populations, but not others, and that knowledge comes from our understanding of genetics.

There's so much that we understand about our genomes today. We understand genetic susceptibility. We know of mutations within our genome that can cause certain types of diseases, or indeed responses or reactions to certain drug treatments.

At the same time, there's an awful lot that we still don't understand. Genetics can be incredibly complex traits such as, for example, body mass or height or cardiovascular disease. Many different elements in the genome collectively contribute to how tall someone is or how likely it is they're going to develop a heart condition.

We understand quite a lot about how different elements in the genome interact to bring about a certain outcome in a given individual. What we are much less good at understanding, just because of the degree of complexity of the problem, is how that genetic component, if you like, plays out against the environment.

In some cases, it's a little bit simpler than in others. Take the example of height: it's not surprising that in addition to that genetic component of height, there will be an important nutritional component to it. If somebody is malnourished, they're unlikely to reach their full potential to reach a height that they could otherwise. But other examples are much more complex than that.

We are still so far from fully understanding and being able to predict how a certain genome will behave in different sets of environments. This is probably one of the greatest and most interesting challenges that lies ahead of human genetics today.