Alec Jeffreys in Conversation with John Armour

Centenary News

Alec Jeffreys in conversation with John Armour Eureka Moments: the Golden Age of Genetics Downloaded from http://portlandpress.com/biochemist/article-pdf/33/4/38/3442/bio033040038.pdf by guest on 02 October 2021

Amy Cox (Communications Manager)

As part of our Centenary celebrations, a number of the Society’s Honorary Members have been asked to talk about the important moments in their careers and the future of the discipline. These interviews will be made available throughout the year on the Society’s website as a series of podcasts.

The fourth to be released is that of Alec Jeffreys who possible applications and, barely a year later, a whole spoke to his former PhD student John Armour about new world of forensic DNA suddenly opened up working in the golden age of genetics. with a massive impact on court case work, paternity When Alec started his career it was a challenge to and immigration. read long DNA and, at the time, there was only one John Armour explained the cultural importance tool available to manipulate it: an enzyme which cut of the discovery, “The point about a DNA fingerprint it in the middle of a particular combination of bases. barcode is that you could just look at it and an non- Alec knew that eventually he would find someone expert could look at it and show what was going on. with a mutation in a site the enzyme recognizes, Was this sample the same as the blood stain found resulting in a longer section than normal. This would be the first direct example of genetic variation. Alec remembers the day he found one in a technician working in the department, “The first thing we asked of that was ‘okay, we can see this variant, this is either a new mutation or it was an established variant out there in the population.’ If it was an established variant, then it must be present in one of her parents and, if I remember right, it was her father who was the carrier.” But these single nucleotide polymorphisms (SNPs) like the one detected in Alec’s technician were too few and too hard to find. So Alec went on the hunt for a more useful marker. Alec found repeated sequences of DNA in the human myoglobin gene and called this new type of DNA mini‑satellites; he used the same technique as before, but this time the variation in length would come from the different numbers in tandem repeats. Alec discovered that, luckily, mini‑satellites across the genome shared the same repeated motif, so they could all be marked using one chemical highlighter. The revelation of this barcode‑like result immediately had Alec’s mind bursting with Alec Jeffreys

The interview being filmed on the skirting board? Are these twins identical? Are and that crucial gene is a mini-satellites. So in the these people related? You could see it as a pictorial course of a 25 year career, Alec has come full circle human exercise in human genetics. You could show from mini-satellites, back to mini-satellites. ■ the inheritance of these high variable pieces of DNA.” Both John and Alec agree that it is rarely possible to predict the outcome of research. Alec explained The Eureka Moments interviews that never, a year previously, would he have written a single word about the potential impact, to have To hear more about Alec’s pioneering work, watch done so “would have been the most monumental the interview in full at www.biochemistry.org/ arrogance that would have assumed (a) that I could Centenary/EurekaMoments get it to work, (b) that I had the wisdom to see where it was going to go, and (c) that anybody would take Previous interviews can also be viewed on the any notice of this whatsoever.” Biochemical Society website: Alec’s discovery of genetic fingerprints was a major achievement but it was not the end of the The key that unlocked calcium: Sir Michael Berridge story. It turns out that mini-satellites play a role in talks to Robin Irvine how DNA is shuffled between generations. This genetic recombination was though to occur randomly The protein that disappeared: Sir Tim Hunt talks to but Alec noticed that the DNA only crosses over at Sir Hugh Pelham particular hot spots. The question was why hot-spots appear where they do in the genome. There is one Making proteins, making a difference: Michael crucial gene which controls where hot-spots land Neuberger and Brian Hartley talk to Sir Greg Winter