How is the completed human genome sequence being used?

Effectively, the completed sequence of the human genome provides an instruction manual for making and maintaining the human body. The task for scientists now is to read the contents of this instruction manual and work out how all the parts fit together and what it all means. The completion of the human genome is just the starting point for a century or more of new discoveries. A number of genome sequencing projects have been set up since the Human Genome Project to start to understand genome biology. You can read about some of them below.

Francis Collins, director of the NIH and one of the leaders during the Human Genome Project, talks about how the completed human genome sequence has been used to tell us more about how to prevent and treat human disease.

International HapMap Project

In October 2002, the International HapMap Project was launched. Building on the freely available sequence produced by the Human Genome Project, it aimed to speed up the discovery of genes related to common illnesses such as asthma, cancer, diabetes and heart disease by creating a ‘catalogue’ of common genetic variations in humans. The catalogue describes specific variations in our DNA, where they occur and how they are distributed among populations around the world.

The DNA sequence of any two people is 99.5 per cent identical.

The DNA sequence of any two people is 99.5 per cent identical. Any variations however, can have a significant effect on an individual’s risk of developing a certain disease. During this project, the scientists looked for sites where the DNA sequence differed by a single base (A, C, G or T). These sites are known as single nucleotide polymorphisms (SNPs). Sets of SNPs on the same chromosome tend to be inherited in blocks. The pattern of these blocks in our chromosomes is called a haplotype. A HapMap is a map of where these haplotype blocks are located on the chromosome. This is useful because, by comparing the HapMap of different individuals, scientists can then identify key areas of genetic variation.

Having a catalogue like this has made it much easier to establish connections between particular genes and disease.

The $100 million public-private effort involved the work of scientists and funding agencies from Canada, China, Japan, Nigeria, the United Kingdom and the United States. It studied a range of populations carefully selected for their diverse population histories.

The first draft of the HapMap was completed ahead of schedule in February 2005, with the final results published in 2010. Having a catalogue like this available to scientists has simplified the search for different gene variations as much as 20-fold, making it much easier to establish connections between particular genes and disease. Between 2005 and 2012, scientists identified a considerable number of associations between particular regions of the genome and disease.

ENCODE project

In September 2003, the National Human Genome Research Institute (NHGRI) in the USA, launched a research project named ENCODE (the Encyclopedia Of DNA Elements). This project aimed to identify and characterise all the functional parts of the genome, and so begin to reveal how the genome actually works. Like the Human Genome Project, it was committed to being a community resource, sharing its data as soon as possible.

The project started with a pilot study. This was intended to test and compare the computational and experimental methods needed to develop an encyclopaedia of all the functional elements in the human genome. The pilot phase brought together investigators from a wide range of backgrounds to help develop the best approaches to the project, evaluating their various merits.

The lead researchers describe the ENCODE resource as an operating manual for the human genome.

In September 2012, after years of effort by hundreds of researchers, a whole catalogue of genetic data was published. The lead researchers described the ENCODE resource as an operating manual for the human genome. As well as confirming the number of genes that carry the codes to make proteins (around 21,000), they identified another 9,000 genes that have important effects in our cells. They also announced that 80 per cent of the human genome sequence is close to regions that control biological function; this meant that most of what was once considered “junk DNA”, the non-coding DNA in the human genome, is actually functional.

The sheer scale of the data collected by the participants of the ENCODE project was overwhelming. Over 1,800 genome-wide experiments were completed, using 147 different cell types and a carefully selected set of new technologies.

Based at the Wellcome Trust Sanger Institute, the GENCODE Consortium was a sub-project and vital part of ENCODE. Their work is helping to describe, in a highly accurate way, the features and functions of our 20,687 individual genes and their various regulatory elements.

1000 Genomes Project

The 1000 Genomes Project, which launched in 2008, was the first project to aim to sequence the genomes of a large number of people (at least 1,000), to provide a comprehensive resource on human genetic variation.

The genomes of over 2,500 anonymous people from 26 populations will be sequenced using next-generation sequencing technologies.

Any two humans are around 99.5 per cent the same at the genetic level. The tiny percentage of genetic material that varies among people can help to explain individual differences in susceptibility to disease, response to drugs or reaction to environmental factors. Although 0.5 per cent may not sound like a lot, 0.5 per cent of 3 billion bases is 15,000,000 – so that’s still a lot of differences!

The 1000 Genomes Project aimed to produce an extremely detailed catalogue of human DNA variation to help scientists studying people with specific diseases. The genomes of over 2,500 anonymous people from 26 populations around the world were sequenced using next-generation sequencing technologies. The final papers from the project were published in Nature in 2015. The results of the study are freely and publicly accessible to researchers worldwide.

UK10K

In 2010, the Wellcome Trust launched a study of 10,000 human genomes in the UK, which aimed to analyse the DNA of one in every 6,000 individuals in the UK. Scientists expected the UK10K project to uncover many rare genetic variants that are important in human disease, giving a much deeper picture of genetics to help other studies, both in the UK and around the world.

The Wellcome Trust provided a £10.5 million Strategic Award to the Sanger Institute to fund the project. It is running in collaboration with clinical researchers from around the UK, using samples and data collected over many years.

UK10K aimed to analyse the genomes of 4,000 healthy people, studied since they were born in the early 1990s, and compare them with the exomes of 6,000 people currently living with a disease of suspected genetic cause, such as severe obesity, schizophrenia or congenital heart disease. By doing this, UK10K aimed to identify the regions of the genes involved in these diseases. Initial results published in 2015 identified genetic variants with links to health and disease, including cholesterol levels and bone health.

The researchers believed that the results from this huge study would have an immediate impact on genetics, contributing to an on-going transformation of our understanding of human genetic variation. Scientists hope that this will lead to advances in our understanding of disease biology, eventually leading to improved treatments.