Discovering the hidden data in our DNA

“DNA fingerprinting has meant a revolution in forensic investigation and in proving paternity and kinship” Professor Sir Alec Jeffreys FRS, University of Leicester

During early investigations into the variation and evolution of human genes, Sir Alec Jeffreys discovered a remarkable property concealed within human DNA.

"We'd got to the point where we could detect single copies of human genes – which led to one of the first observations of introns, non-coding sections of DNA that split up genes. But when I came to Leicester in 1977, I wanted to move away from the study of split genes, and to marry the new techniques of molecular biology with human genetics," he explains.

His plan was to use gene detection techniques not only to look at the structures of genes but also to understand inherited variation between people. "We knew about heritable variation in gene products such as blood groups, but we were looking for inherited variation at a far more fundamental level, namely in DNA itself.”

An accidental breakthrough

The first examples of DNA variation proved to be rather uninformative and tedious to detect. The question therefore was whether far more variable regions of human DNA exist. The breakthrough came from a different project in Professor Jeffreys' lab.  While looking at the human myoglobin gene, which produces the oxygen carrying protein in muscle, he noticed an intron in that gene containing tandem repeat DNA – short sequences repeated a number of times – which became known as minisatellites. He reasoned that these minisatellites had the potential to be highly variable in terms of numbers of repeats.

The team identified more minisatellites and to their surprise discovered a core sequence - a piece of DNA that is similar in many different minisatellites. This chemical similarity allowed him to develop a method for detecting many minisatellites simultaneously. He tested this idea on a panel of DNAs, and by accident produced the very first DNA fingerprint, a complex pattern of bands on an X-ray film. "I took one look, thought 'what a complicated mess', then suddenly saw we had some extraordinarily variable patterns," he says. "There was a level of individual specificity that was light years beyond anything that had been seen before. It was a 'eureka!' moment. We could immediately see the potential for forensic investigations and paternity, and my wife pointed out that very evening that it could be used to resolve immigration disputes by clarifying family relationships." That first X-ray film also had a range of animal and plant DNA samples, and showed that the same technique worked not just on humans, opening up exciting possibilities in conservation biology, ecology and wildlife forensics.

From the laboratory into the real world

It took only a few months for the technique to be refined into clean barcode-like patterns that allowed DNA fingerprints to be interpreted clearly.  Professor Jeffreys was able to develop practical testing methods using these DNA profiles to determine whether samples were from the same person, relatives, or non-related people. Since his groundbreaking work in the mid-eighties, DNA analysis in forensic cases has become universally adopted and has meant a revolution not just in forensic investigation but in proving paternity and kinship, reuniting families as well as serving justice.

Ongoing research

Professor Jeffreys is currently investigating the fundamental forces that create all human DNA diversity, namely mutation and recombination, without which we would all be genetically identical. His work is not only shedding major new light on these processes but also has practical applications in areas ranging from mutation detection to identifying environmental factors that can influence the incidence of heritable mutations. His colleagues are using his systems to study families exposed to radiation following the Chernobyl disaster. They have also shown, in mice at least, that DNA instability induced by radiation can itself be inherited from one generation to the next, raising concerns about the long-term genetic consequences of exposure.

Supporting Professor Sir Alec Jeffreys’ work

Professor Sir Alec Jeffreys was made a Fellow of the Royal Society in 1986 for his distinguished work in genetics. Since 1991, he has been one of the Royal Society’s Research Professors, working in the Department of Genetics at the University of Leicester, and his Royal Society professorship is funded with support from the Wolfson Foundation.