Tuesday, 7 April 2015

The science behind DNA fingerprinting

This week's TV drama "Code of a Killer" is perhaps best described (by one critic) as "workman-like". I can't comment on the accuracy of the portrayal of the policeman, but the role of Alec Jeffreys, or rather the depiction of a Molecular Biologist at that time, is more  clichéd than I would have  a liked. However, I think the Science has been explained pretty well. Although it can't compete with Daniel Craig's explanation of "Uncertainty" in Michael Frayn's "Copenhagen" when he (as  Werner Heisenberg) meets Niels Bohr; or Tim Piggott-Smith's masterful explanation (as Francis Crick) of the significance of Rosalind Franklin's diffraction data (above) in "Life Story" (the drama behind the determination of the double helical structure of DNA). 

DNA Fingerprinting
The challenge that Alec Jeffreys faced, is one of the most fundamental aspects in genome science: on the one hand Darwinian evolution leads us to look for the similarities between genes in say mice and men. However, what is important in forensics (and paternity testing) are the elements in our genomes that make us different. These are the "stutters" that are mentioned in the drama. The image on the right shows a series of DNA fragments which have been "highlighted" through the use of a radioactive "probe" designed to "pick out"  DNA sequences complementary to the probe itself. In this way a scene of crime sample can be identified as that of suspect 2. Recall that the phenomenon of base pairing is a key component of the structure of DNA in which the bases G and C and A and T form "complementary" pairs. So, if a fragment of DNA contains the sequence 5'GATTCCGGATTCA3' (for example), then the probe sequence 5'TGAATCCCCGGAATC3' would "hybridise" to it. If the probe was radioactively (or fluorescently) labelled, then the complementary sequence separated on a gel (agarose for long fragments and polyacrylamide for short fragments of DNA) can be "visualised" using a suitable film or detector. When Alec Jeffreys is shown trying various probes to explore similarities and differences in genes. His focus on the seal myoglobin gene is shown because this is where he obtained the first high quality data, from a highly variable sequence, linked to a common core sequence within an intron in the myoglobin gene. 

Let me try to simplify. While many labs in the late 1970s were studying the generic properties of genes, Alec Jeffreys (left) was interested in human genetic variation. For example, in the USA, Richard Roberts and Phil Sharp were about to announce their Nobel Prize winning discovery of introns; that is non-coding sequences of DNA that are interwoven between the exons (coding sequences) in the human (and most eukaryotic) genomes. Back in Leicester, Alec Jeffreys was more concerned with obtaining an experimental handle on those regions in our chromosomes, where there had been (over evolutionary time) less selective pressure to maintain integrity, i.e. where variation in sequence was and is tolerated. These regions, often called mini-satellites are typically flanked by common sequences. Hence, if you can design a "probe" to reveal the number of  copies of a repeated sequence, or one that will pick out the common element and it bring with it the number of variable sequence, then using restriction enzymes (recall these are the sequence-specific DNA cutting enzymes) or more recently PCR-based strategies, it is possible to compare individuals in such a way that the differences are highlighted. Importantly, as Jeffreys proved, when you get this right, these differences are sufficiently distinctive and statistically robust, making identification (or importantly in the case highlighted in the drama) elimination of a suspect both possible and definitive. If you recall the scene in the drama where the investigating officer is in his office with his second in command and Alec Jeffreys explains the experimental data: the scientist must be completely confident in advising the police that their prime suspect is not the culprit. Today this genetic "bar coding" forms a major element in any identification process, ranging from crime scene investigations, through parental disputes to the tragedy of the identification of victims in warfare or, as we have recently witnessed, the passengers on Germanwings flight 4U9525. 

For me Alec Jeffrey's work and its application, represents one of the finest examples of how "Blue Skies" science can improve our world. Not surprisingly, Professor Sir Alec Jeffreys has since then, been given many accolades. In my view, there couldn't (in my view) be a more deserving scientist.

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