DNA fingerprinting and national DNA databases 24/02/04 by Giles Newton In part 3 of the DNA fingerprinting story, Sir Alec Jeffreys discusses the introduction of PCR to DNA fingerprinting and the launch of the National DNA database, and argues for a DNA database for all citizens.

Part1: Discovering DNA fingerprinting

Part2: DNA fingerprinting enters society

DNA profiling was first used in criminology in 1986, and quickly became accepted worldwide. Forensic scientists soon wanted to establish a database of DNA profiles, but they needed an even more efficient system. The arrival of the polymerase chain reaction (PCR) revolutionised identity testing.

The initial technology behind DNA fingerprinting and profiling involved taking people's DNA, separating it on a gel, attaching a radioactive probe – targeted to a minisatellite – to the gel, and developing the bands on X-ray film. While effective at producing highly discriminatory patterns, the technology was slow, cumbersome and manual – it couldn't be automated.

The answer to the problem, as indeed it has been to so many areas of molecular biology, was the polymerase chain reaction. "PCR – as a terrible version – was first developed in 1983, and as a usable version by 1988," says Professor Jeffreys. "It really is a superb technology, and we started using it immediately."

Technology centre: Polymerase chain reaction

Moving DNA fingerprinting to a PCR-based technique was not straightforward, however. PCR is limited in the number of bases DNA it can amplify (at the time the limit was 1000-2000 base pairs), and many minisatellites are much, much bigger. The technique therefore required smaller bits of DNA that showed the same tandem repeat variation. In 1988–89 came the first reports of microsatellites, also known as 'simple tandem repeats'. These repeat regions played a huge part in the Human Genome Project, as researchers could use them as landmarks when mapping and sequencing the genome. For DNA profiling, the microsatellites seemed ideal: they were much smaller than minisatellites and could be readily amplified by PCR, yet they still showed the variation essential to the technique.

Minisatellites vs microsatellites

Minisatellites

• Repeat unit length – 6-100 bases
• Two to several hundred repeats at each minisatellite
• Thousands of different minisatellites scattered throughout the genome, but often clustered near the end of the chromosomes – the telomeres.

Microsatellites

• Repeat unit length: 1-7 bases
• 5 to 100 repeats at each microsatellite
• Thousands of different microsatellites, randomly scattered throughout genome.

Professor Jeffreys and his team quickly adapted DNA profiling to use microsatellites and PCR, and took on two cases to see if it would work.

The body in the carpet

Buying a house can be a stressful time, but surely not as stressful as a house purchaser in Cardiff who moved into their new residence, dug up the patio and found a buried carpet. Inside the carpet was a skeleton.

"It was a fairly safe bet this was a murder case," says Professor Jeffreys. "A facial reconstruction from the skeleton was put out in the press and on Crimewatch. Someone phoned Crimewatch and suggested that it was a girl called Karen Price who had gone missing about ten years previously."

Working with Erika Hagelberg, an expert in bone DNA extraction and analysis, DNA was extracted from the skeleton and Professor Jeffreys compared it to DNA from Karen's mother and father; it was indeed their daughter.

This was enough to give the police a secure basis for identification. A murder enquiry was launched, which led to the identification of the murderer and accomplice. The evidence went to Cardiff Crown Court in 1991 – the first time PCR and ancient bone DNA evidence had been presented to a court in the UK. "It was a lot of firsts for the court to handle, but the evidence was accepted and the perpetrators were convicted," says Professor Jeffreys.

Mengele's bones

The second case that helped establish PCR and microsatellites in DNA profiling involved the Auschwitz camp doctor Josef Mengele. Caught by the Allies at the end of World War II, Mengele escaped to South America. In 1979, a man who might have been Mengele drowned at sea and was buried. Following a tip-off that the body in the grave in Sao Paolo, Brazil, might be Mengele, the skeleton was exhumed.

"The DNA analysis was very difficult," says Professor Jeffreys. "We only had trace amounts of DNA from badly decomposed bones, but enough to compare with with blood samples from Mengele's wife and son, who were still alive in Germany. It was like a paternity case in reverse."

The results showed, with 99.9 per cent certainty, that it was indeed Mengele. The evidence went to Germany, the Simon Weisenthal Institute and the US Department of Justice, and the 40-year war crimes investigation was finally closed.

National DNA databases

It took a few years for PCR to become established, but it took off in the UK in 1995, with the development of the National DNA Database.

"The Home Office Forensic Science Service had to take the technology to the point where it could be used for databasing – and they did a brilliant job," says Professor Jeffreys. "They simplified the technology, automated it, and launched the world's first criminal intelligence DNA database in April 1995."

Feature: Ethics of the National DNA Database

There are now more than 2 million people on the database – thought to include a substantial proportion of habitual criminals. Even so, if DNA is found at a crime scene, in about 60 per cent of cases there is no match in the database – the offender is someone without a record. There have therefore been extensive discussions about how to expand the database.

One option that is being discussed is to permit the retention of DNA from suspects (which is usually discarded). "I find this highly discriminatory," says Professor Jeffreys.

Another concept that is being discussed is the 'DNA photofit', perhaps linking DNA to hair colour, eye colour, or facial features. "This is fanciful at the moment," says Professor Jeffreys, "but is it wise to allow the police to investigate markers that give a lead on your ethnic origin or facial features? The police would be accessing genetic characters that are important to you as an individual."

"One has to be exceedingly careful with this kind of approach, as there are huge moral and ethical issues. There are no such problems with microsatellites, as they are not biologically relevant - it doesn't matter whether you have ten or 20 repeats."

Is there a more secure way of tracing criminals if there is no lead from the database? Professor Jeffreys thinks there is: "The answer is simple – expand the current database to include everyone," he says. "It gets around the discrimination problem: if we're all on the database, no one is being discriminated against. But this global database should not be held by the police, as that would send out all the wrong signals."

Instead, he argues, we should regard DNA profiles as providing a certificate of identity. "We're all used to birth, death and marriage certificates. Imagine an equivalent of Somerset House holding DNA identity profiles. It would give you protection as an individual, proving that you are you."

Image credit: Neil Leslie

Further reading

Jeffreys AJ, et al. Identification of the skeletal remains of Josef Mengele by DNA analysis. Forensic Sci Int 1992 56: 65-76. Abstract