This Week in Science History - The Invention of DNA fingerprinting

This week in science history saw, in 1984, the invention of DNA fingerprinting by Sir Alec Jeffreys. Since then, the technique has been used in thousands of paternity and criminal cases around the world.

Jeffreys had been working at the University of Leicester for seven years when he made his discovery. We know that variation in features such as eye colour and blood group are heritable, i.e. are passed on from parents to children and are easy to test for. Jeffreys and his team were interested in whether small changes in the DNA code itself could be found, as being able to detect these tiny changes and whether they are inherited could be used to tell people apart or tell if they were related.

Looking at something like the gene for blood group, you would not necessarily be able to say if two people were related or if two blood samples came from the same person, as there is so little variation - just A, AB, B and O - meaning that lots of people in the world have each blood type. In order to tell people apart using their DNA, the team began looking for pieces of DNA that would show more variation.

This led them to pieces called VNTRs - variable number tandem repeats, basically pieces of DNA that have repeats of a sequence of bases. There are four bases - adenine, thymine, cytosine and guanine (or A, T, C and G) that make up the genetic code. The order they are found in the DNA determines whether you have blonde hair, brown eyes or diseases such as cystic fibrosis. In a variable number tandem repeat area of DNA, there would be a 'core sequence' of between 10-80 bases, that would be repeated anywhere between one and twenty times in that piece of DNA, with the number of repeats being inherited from your parents. These repeats occur in many places in the human genome. The first variable number tandem repeat that Jeffreys and his team found was in the gene for myoglobin, an oxygen carrying pigment found in muscle. They were able to create a 'probe' for the core sequence, which could find the sequence anywhere that it was present in the DNA code.

The 'eureka' moment occurred at 5 past 9 in the morning on September the 10^th1984. Jeffreys was looking at the results of an experiment they had carried out using the DNA of his lab assistant and her parents, to see if the probe they had created would show up inherited variations in the length of the sequence repeats. A clear pattern was visible, showing the differences in the lengths of the repeats between the assistant and her parents, but also which of the repeats she had inherited from each parent. Jeffreys immediately understood the importance of this technique for resolving paternity disputes, immigration cases and criminal cases.

Since the late 1990s, sequences of DNA called short tandem repeats, similar to the variable number tandem repeats discovered by Jeffreys, have been used. As the name suggests, short tandem repeats contain a much smaller 'core sequence' of between two and 10 bases, compared with between 10 and 80 for the variable number tandem repeats. These are less damaged by degradation of a DNA sample than the larger variable number tandem repeats, making them much more useful in a forensic case, where DNA from a crime scene might have been affected by time or the elements.

This is how DNA fingerprinting is carried out today. The DNA from a sample such as a mouth swab, blood sample or swab from a crime scene is extracted and purified. In order to isolate the short tandem repeats, a procedure called PCR is carried out on the DNA. PCR chops out and replicates specific parts of the DNA - in this case the short tandem repeats, amplifying the amount of these parts in the sample. The DNA will then be run on an agarose gel to separate out the different sized short tandem repeats using the fact that DNA is charged and will move through the gel when an electric current is passed across it. A long repeat where the core sequence is repeated say one hundred times will pass through the gel more slowly than a smaller repeat as the piece of DNA chopped out and replicated will be larger. It's a bit like if you have a tank full of golden syrup and drop two balls of equal weight but different size into it - the bigger ball will take longer to reach the bottom of the tank. If you took a photo after 10 seconds, the bigger ball would be higher up in the tank than the small one. If you kept running a gel, then all of the DNA would move through it to the other side, pulled by the electric current. But if you stop the electric current after a given time, the DNA will stop moving and will be separated out by size. In order for us to see the positions of the short tandem repeats in the gel, a dye must be used. This can either be added to the sample before it is run through the gel, or washed over it to pick out the short tandem repeat pieces after the gel has been run. When the pieces of DNA are shown up by the dye, they appear as distinct bands on the gel. It is the pattern of bands, showing the presence of different sized repeats that is analysed to show if a sample has come from a particular person.

电视节目像CSI和沉默的证人, DNA fingerprinting is used in criminal cases to link suspects to a scene or to a rape victim, or to find the identity of a body, but a relatively new use of the technology is for conservation. It is being used at Zurich zoo to investigate how the flock of rare Ibis birds there are related, so that they can prevent the birds from inbreeding, something that is damaging to the health of the species.

There are some concerns about the use of DNA profiles, particularly with regard to DNA databases. In the UK, currently the police can hold DNA information of people who were arrested but not charged, raising concerns about civil liberties. Alec Jeffreys himself believes that although a DNA database is in theory a good idea for person or body identification in emergencies or after disasters like the 2004 Indian Ocean tsunami or 9/11, they should not be held by police.

Countless criminal and paternity cases have involved DNA fingerprinting over the last twenty five years. It has allowed dangerous and violent criminals to be put away. There are occasional problems, particularly as such care must be taken to prevent contamination, but it is an essential tool in the fight against crime, and growing in use for conservation of rare species.