Department of Genetics

Fingerprinting

to the Future My life changed on “ Monday morning at 9:05am, th “10th September 1984 25 Anniversary

This was the morning of Professor Sir Alec of DNA Jeffreys’ ‘Eureka moment’ and the discovery Fingerprinting of genetic fingerprinting at the University of Leicester. In the 25 years that have followed, genetics at Leicester has continued to go from strength to strength. As an internationally renowned centre of pioneering research, the Department continues to push back the frontiers of knowledge in genetics.

www.le.ac.uk/genetics 2 UNIVERSITY OF LEICESTER · DEPARTMENT OF GENETICS

The implications of the discovery of DNA fingerprinting were to become massively far reaching, with applications in solving crime, testing paternity, twin studies, conservation and diversity and immigration, amongst others.

The first of these applications came just the next year, a decade earlier than Sir Alec had anticipated. The dispute involved a family of UK citizens, originally from Ghana, whose son was refused re-entry to the UK after his passport was damaged.

DNA evidence proved the boy was a could not have been responsible for full member of the family and the case either. 5000 local men were then asked was dropped. Sir Alec said; “Our first to volunteer blood or saliva samples. The application was to save a young boy true killer, Colin Pitchfork, persuaded a from wrongful deportation and it colleague to give a blood sample on his captured the public’s sympathy and behalf. When this was discovered, imagination. It was science helping an individual challenge authority.” “ Our first application was to save The first forensic case also captured the a young boy from wrongful public imagination, with the solving of two murders in the Enderby area of deportation and it captured the Leicestershire. A man had been public’s sympathy and arrested and confessed to one murder but not the other. The police decided imagination. It was science to utilise genetic profiling, expecting to helping an individual challenge prove him guilty of both crimes. Instead Dolly the first mammal ever to be cloned. the genetic results showed that he authority.” FINGERPRINTING TO THE FUTURE 3

Pitchfork was arrested and his profile biomedical research in Europe, and this tremendously old, obviously, with a was found to match that found at the was swiftly followed by the Albert long white beard, and also totally crime-scene. He was later imprisoned for Lasker Award for clinical medical terrifying.” In fact the power of this 30 years. research, and the Dr HP Heineken Prize “mythical me” has grown to such an for Biochemistry and Biophysics. He extent over the past five years that he Since these cases, DNA fingerprinting was voted the Morgan Stanley Great finds people who don’t know him has been used in countless ways, from Briton in 2006 and is an honorary sometimes arrive “literally trembling as solving crimes, to paternity cases, freeman of the City of Leicester. they come into the presence – it’s just through to proving the origin of Dolly so ridiculous”. the sheep, and exonerating death row The result has been, he says, to create prisoners through the use of DNA two Alec Jeffreys. “There is the me In fact, he says, the real me has barely evidence. The first such case was that of that you see sitting in front of you, changed at all over the years. “None Kirk Bloodsworth who was convicted of scruffy, enjoys getting his hands dirty, of this fame or all the rest of it has sexually assaulting and murdering a nine has a beer with the rest of them, and gone to my head,” he says. “Quite year old girl. Bloodsworth was that’s the bit of me that thoroughly often I find it a complete pain in the sentenced to death for these crimes and enjoys the science.” And then there’s butt because I just want to get on with served eight years in prison, two of the “mythical me”. “First I’ve got to be the science.” which were on death row. However DNA tests conducted in 1992 proved Bloodsworth had not committed the crimes and he was released from prison in 1993.

Child MotherFather “ In 1984 I sat in a prison cell waiting to die for a crime I didn’t commit. I read about the work of Sir Alec Jeffreys and I had an epiphany: this could prove my innocence and set me free!”

Meeting Sir Alec at the 2004 pride of Britain Awards, he said,”In 1984 I sat in a prison cell waiting to die for a crime I didn’t commit. I read about the work of Sir Alec Jeffreys and I had an epiphany: this could prove my innocence and set me free!”

Alongside the massive practical implications, the discovery has also DNA Fingerprinting brought Sir Alec Jeffreys global The first DNA fingerprint was created at 9.05am on Monday 10 September 1984. Highly variable repeated parts of DNA called recognition. He was elected to the ‘minisatellites’ could be clearly seen, and in 1988 Sir Alec was able to Royal Society in 1986, and was describe the mutation rate between parents and their child’s DNA at awarded a knighthood for services to these mini satellites. genetics in 1994. Ten years later he received the Louis-Jeantet Prize for Medicine given to scientists distinguished for the highest quality of 4 UNIVERSITY OF LEICESTER · DEPARTMENT OF GENETICS Genetics at Leicester – the next 25 years Research in the Department has certainly not stood still since 1984

Since the establishment of the Department in 1964 with just seven members of academic staff, the Department has continued to grow its international reputation for research. There are now more than 20 academic staff members leading independent research groups, and the total size of the Department is around 140 strong, with an international flavour that is testament to its worldwide reputation. FINGERPRINTING TO THE FUTURE 5

Genealogy Current research in the Department has far reaching consequences for diverse areas such as genealogy, which Sir Alec predicts likely to emerge as a key application of the new gene technology – a kind of “Genes Reunited”. The current Holy Grail of geneticists is to churn out the human genome sequence for $1,000, and the price is bound to fall even further. Once anyone can pop down the high street to Genes R Us, have a quick mouth swab, and pick up their sequence for a few hundred pounds, what will they do with it? Jeffreys suggests that they will use it to identify others whose genome shows similar patterns of DNA, and Genetics United Nations: The Department currently includes members from 31 different countries therefore must be closely related. And they won’t just be able to identify their contemporary relatives. In theory, if you had importance of genes to the workings of conducting blue skies research to deliver the total genome sequence of everybody in biological clocks. answers to questions “that you never Britain you could go some way towards knew existed, and that to me is infinitely constructing the complete genealogy of the Crime more valuable because that sets the future UK going back hundreds of years. agenda.” A more controversial prediction is that at This will also have wide reaching least one country in the world will soon While the Department of Genetics has consequences for social history, enabling us introduce a DNA database of its entire inevitably changed in the 30 odd years he to trace patterns of social change through population. Jeffreys has spoken out about has been there, and expanded to around the movement of families. the UK’s police database holding DNA three times its original size, he believes its profiles of innocent people on the grounds fundamental ethos remains the same. Medicine that it only covers those who happen to Students, while perhaps more concerned have been stopped by police. But he is about their future employment prospects Another vital future impact is likely to be in more ambivalent about the idea of a than their equivalents in the 1970s, have the world of medicine. Over the next 25 years, Jeffreys says, a much more detailed universal database run independently from not changed in quality or their level of catalogue of genetic variants and their the police and able to identify bodies from enthusiasm, and staff have been ability to combat diseases will become mass disasters such as the Asian Tsunami, consistent to the principles of Bob available. Huge steps have already been or even regular traffic accidents. He Pritchard, who founded the Department made in identifying genes that affect proposes that this database should hold almost along the lines of a commune, says diseases such as Type 2 diabetes, not DNA profiles but DNA ‘PINs’ derived Jeffreys “where there are no prima schizophrenia and manic depression, but from scrunching down DNA profile donnas, everybody gets on in a good over the next few years further progress is information. This would create merely an collegiate interactive way with each expected in discovering how genes work identity number and remove information other”. This was what attracted Jeffreys in not just individually but with each other, on personal traits or family relationships. If the first place and he maintains that “that and with the environment, to cause and police wanted access to this database they sense of community, that sense of glue combat disease. Scientists are also would need a court order. “I’m not saying holding us all together in a common beginning to understand more about how we should even go down this road,” he purpose is as strong as ever”. genes affect stature, eye colour and other says. “I’m saying this is a road that has What is more, Jeffreys says, people stay. traits unconnected with disease in which not been properly discussed.” Even PhD students who go off to do a individuals differ from each other. postdoc elsewhere often return. “There is Fundamental Ethos Research in this area is being pioneered in some remarkable magnet that draws them the Department with significant moves One of the reasons why Sir Alec has back to this place, and I think if nothing towards identifying causes and effects of chosen to stay at Leicester, despite offers else it is that sense of friendliness and gene mutations and work in identifying the to move elsewhere, is the excitement of camaraderie.” 6 UNIVERSITY OF LEICESTER · DEPARTMENT OF GENETICS FINGERPRINTING TO THE FUTURE 7

Radiation’s Legacy

Described as one of his highest points since 1984, Sir Alec defied colleagues around the world by developing a technology that they said would be impossible, telling him: “you’d never get this to work”.

He devised a technique which would radiation can directly cause heritable greatly enhance a scientist’s ability to see mutations in human DNA. how DNA changed between In April 1986, an explosion ripped generations. This enabled the DNA of through the Chernobyl nuclear power millions of sperm to be examined to plant in Ukraine, contaminating large directly measure the mutation rate and parts of Ukraine, Belarus and Russia for first time observe minisatellites or with radiation. Professor Dubrova other regions of DNA before and after studied the genes of 79 families in the the mutational changes occurred during region around Chernobyl to examine the process of sperm production. By the influence of the accident on gene using direct evidence from sperm mutation. In the Chernobyl region the analysis, Sir Alec armed himself with the genetic mutation rate was found to be knowledge that these minisatellites were unusually high, with parents in the highly unstable. He then moved quickly area passing on mutations to their to try and unravel the secrets of when, children more than elsewhere. how and why these DNA mutational Professor Yuri Dubrova changes occurred. The findings from this research have led to further studies into the causes of This led to research into rare ‘direct elevated mutation rates continuing into childhood leukaemia. The incidence of mutation events’. Sir Alec and Professor the second generation of offspring. this cancer in Britain increased Yuri Dubrova, another distinguished dramatically during the twentieth Commenting on the results of this human genetic scientist in the century. The increase has mainly study, Dubrova said “Experimental Department of Genetics, were primarily affected the under-five group, in whom evidence for radiation-induced concerned with how the environment risk increased by more than 50 per heritable mutation in humans remains has an effect upon DNA which is highly controversial. But our studies in cent during the second half of the inherited between generations. Professor Ukraine and Belarus have shown that century alone. Dubrova completed some major studies genomic instability can be induced in in humans from regions affected by the Studies with mice showed that radiation exposed fathers. It remains to 1986 Chernobyl disaster and parts of mutation rates in unexposed offspring be seen whether this instability can be Kazakhstan where Russia tested above of exposed male mice maintain transmitted to further generations, as ground nuclear weapons. This work led mutation levels similar to those of has shown to be the case in our to some of the first evidence that directly exposed males, with the mouse studies.” 8 UNIVERSITY OF LEICESTER · DEPARTMENT OF GENETICS

GENETICS AT LEICESTER TIMELINE

1984 Discovery of DNA fingerprinting. 1964 Department of Genetics established. 1988 First detailed description of 1985 the rate of mutation in First immigration case solved humans at the DNA level. by DNA fingerprinting. Home Office made the First paternity case solved by technique available to the DNA fingerprinting. police through a deal with ICI’s Cellmark Diagnostics First identification of identical (now Orchid Biosciences twins using DNA fingerprinting. 1970s Europe Ltd), the company set up to mark Prof J’s discovery. Late 1970s Department 1986 begins to First criminal expand activities investigation to become a to implement world centre for DNA 1977 molecular fingerprinting genetics. evidence. Alec Jeffreys joins the Department. FINGERPRINTING TO THE FUTURE 9

2002 Awarded Queen’s Anniversary Prize.

1992 Identification of Josef Mengele by DNA 2005 analysis from skeletal remains. Establishment of GENIE CETL.

1990s Early 1990s Development of sperm analysis technology.

2002 Department sets up the Institute of 2007 Genetics. Establishment of the Genomics Core Laboratory. 10 UNIVERSITY OF LEICESTER · DEPARTMENT OF GENETICS

Professor Jobling and Turi King (pictured right) researching the Y chromosome chain and genetic links within surnames FINGERPRINTING TO THE FUTURE 11

for the matching of crime scene DNA to potential suspects, in cases where no immediate match to an individual can be found on the National DNA Database. Professor Jobling explains; “If the police had access to a large enough database of names and Y chromosome data, they could run the DNA found at the crime scene against it to see if they could find a Y chromosome match. In 20% of cases this could lead to a surname match, which could potentially help the What’s in police to reduce the size of their suspect pool.”

While police would still need to obtain a full DNA profile, this approach could act a name? as an effective investigative tool, dramatically reducing the amount of Research in the Department looking at genetic links time police currently spend investigating between people with shared surnames may have suspects. wide reaching implications, both inside and outside Traditional Genealogy the realms of genealogy. The research also has implications for traditional genealogy; “This research “Y chromosomes are passed down from only found in 25 people – all in West raises the possibility of tracing surnames father to son in the same way surnames Africa. back to single founders and of linking are. Therefore by studying the Y together branches of family trees by the “It is extremely rare”, said co-author of chromosomes from a series of information written in DNA, rather than the study Dr King, “there are only 25 volunteers, we hoped to identify the birth, marriage and death certificates,” other people known worldwide and degree to which a shared surname also Professor Jobling said. they are all African.” indicated shared ancestry, or ‘hidden This could enable people to research relatedness’”, Professor Mark Jobling, Following this discovery the researchers their family trees more rapidly than has who led the research explained. collected DNA from 18 men with the previously been possible by identifying same surname and discovered that 7 people who share surnames and Within the research group of 150 pairs of them also shared this rare Y undertaking genetic research. of men with shared surnames but no chromosome link. All of the men are known shared ancestry, Professor Jobling white and were unaware of their and Dr Turi King found a 25% chance of African ancestry until the study. Social History a shared surname also resulting in a The research results are also of interest “This study shows that what it means shared Y chromosome and therefore a to social historians. Any illegitimacy in to be British is complicated and always common ancestor. the chain at any stage would have has been”, Professor Jobling says; impacted on the research results as the Removal of high frequency names such “Human migration history is clearly Y chromosome chain would have been as Smith increased the chance of sharing very complex, particularly for an island broken. However the research has to 50% and, when the test was applied nation such as ours, and this study shown that this was rare. in more detail to rare names, such as further debunks the idea that there are Attenborough, this increased to 80%. simple and distinct populations or This shows that the social norms held ‘races’”. today have remained strong throughout African Link the last few centuries. It was during the course of this research Crime scene DNA matching Research into this area may prove a that they made the startling discovery of The results of the original research crucial development, in more ways a rare African Y chromosome, previously could also have massive implications than one. 12 UNIVERSITY OF LEICESTER · DEPARTMENT OF GENETICS

research information which associates DNA genotypes (gene sequence variations) and International widespread phenotypes (common diseases, drug responses etc).

The significance of this project is expected to be immense. When all the world’s gene- Database to Share disease data for disorders such as heart disease, diabetes, obesity are complied and made freely available in one database system, geneticists across the world can Understanding of begin to build an overall picture of what part genes truly play in making human beings what they are. Genome Essentially all humans have the same set of genes, but the precise sequence of those genes varies in subtle ways. Geneticists UK and Indian academics collaborate to make have been studying how different genomics research information available worldwide genotypes and the complex interactions between genes affect characteristics such as disease risk, height, and intelligence, Professor Anthony Brookes, geneticist at Collaboration and mutual contribution are and our responses to medication. One the University of Leicester, UK, was one of at the heart of UKIERI and Professor example is infection by the HIV virus that the first recipients of awards made to Brookes won the award for a joint project causes AIDS. Exposure to this virus does foster research collaboration between India with Professor Samir Brahmachari, Director not guarantee that infection will occur or and the UK, under the UK-India Education of the Institute of Genomics and Integrative that disease will develop. Such risks very and Research Initiative (UKIERI), following Biology in Delhi. Their shared aim is to much depend upon genetic factors, and its establishment by the Prime Ministers of create an Internet-based database system some people appear to be almost immune both countries in 2004. that gathers together a global summary of to contracting this affliction. FINGERPRINTING TO THE FUTURE 13

Scientists are also interested in how Indian and European parts of this slow. It was difficult to pin down what conditions such as obesity, heart disease combined database will come online, and was going wrong. Pallavi has now been and strokes are affected by environment other such resources will hopefully also working with us in Leicester for just two and genotype, and this demands a much join in.” months and we have achieved more in more complex approach than the study of that time than in the previous six months. UKIERI is about people and relationships single genes. In this context, genetics (the Indeed, this visit of the IGIB team has as well as research and its support has study of a single gene) has given way to enabled us to develop certain parts of the enabled the project to facilitate exchanges genomics (the study of all genes). project far beyond what we originally between research staff. Professor Brookes planned. It’s very significant that it is The technologies for this research have only has visited the group in India and Debasis UKIERI that has brought out that been created in the past decade and have Dash, a young scientist of the institute dimension.” only become sufficiently sophisticated for and co-PI in the project along with his widespread deployment in the past couple colleague Pallavi Sarmah have worked in Strengths and ideas have been merged, of years. Aside from cost, the two main Leicester. training has improved and the cultural problems geneticists working in this field and scientific strengths of both groups Professor Brookes explained: “Normally experience are distortion caused by have been maximised. Sharing challenges, collaborations work by dividing tasks working with mixed population groups, the two groups work faster, in a between groups, each of which works and the challenge of false positive signals professional ‘intimacy’ and ‘synergy’ that under its own control. UKIERI (misleading random results that appear to comes, Professor Brookes says, directly collaborations are different. We share the be significant). from the UKIERI support. tasks.” The database being built by Professors Only once an international Internet “It’s very hard for this approach to work Brookes and Brahmachari will significantly database is available, Professor Brookes remotely, since everyone needs to know reduce these problems because of the wide believes, will geneticists be able to draw every little detail, otherwise the overall range of information that will be gathered concrete conclusions about the genetic project just doesn’t gel. The nature of a and included – not least findings from a basis of phenotypes that are free from the UKIERI project – to work jointly – means pan-India assessment of genetic variation distortions of population variability or that you end up with a depth of being conducted by Professor Brahmachari false positives. He admits that ‘the jury is information and mutuality you wouldn’t (the ‘Indian Genome Variation Project’). out’ as to how much of the total genetic normally achieve. You also learn about causation of disease will be each other’s cultures, which is very Professor Brookes explained why the unambiguously revealed in this way, but enlightening and enjoyable”. collaboration with India came about: “We one thing he is quite certain about is that need Internet-based data management, so “Before the UKIERI funding, we worked there will be far slower progress unless that information related to all studies of for six months on one geneticists have one place to the genome can be compiled. Most of the particular aspect of this hold everything studies involve Caucasians, and the group project, and together, to provide working in India wanted to balance this by progress was a holistic view. determining Indian genotypes. They have begun to map genetic variations across India and are now moving on to look at the variations in diseases in India. So what we decided to do was to build a database to store all this information and compile all the results that we and others were generating.

“Many projects that produce primary data are setting up their own databases, but they are typically project-specific and archival in nature. We extract from this raw data the core information and present a summary level view of all these studies. It is a viable project, because such databases are increasingly built and designed on the same model. In a few months time the 14 UNIVERSITY OF LEICESTER · DEPARTMENT OF GENETICS

Biological Clocks

Research by Professor Bambos Kyriacou on Organisms that live on the surface of the planet are clock genes in fruitflies has important applications in society. exposed to relentless cycles of day and night, hot and cold. Over the past 3 billion years, this has lead to the evolution of a 24 hour biological clock, which allows an animal or plant, or even a microbe, “We find the same molecular to anticipate these predictable changes in the components of the clock in environment. krill, fruit flies and humans but This 'circadian' clock, as it is called, is a combination of genetic and the number of clock genes environmental factors. Over the past 30 years, a number of core clock genes and proteins is different” have been identified which build the 24 hour oscillator. Surprisingly perhaps, it turns out that these genes are the same, whether in a mouse, human or a fruitfly, revealing their deep evolutionary roots, “We find the same molecular components of the clock in krill, fruit flies and humans but the number of clock genes and proteins is different.” Says Ezio. Furthermore, a large proportion of gene products, mRNAs and proteins, are expressed in 24 hour cycles at the command of these core clock genes.

A number of surprising links have been made, for example, it turns out that mutations in some clock genes may predispose an animal to cancer. Leicester’s research is exploring some of the implications of clock gene research for human health and well-being in our 24 hour society.

Common fruit fly (Drosophila Melanogaster). FINGERPRINTING TO THE FUTURE 15

Research into teaching

The application of this research into teaching is also crucial to the ongoing success of the Department

GENIE Degrees spent on research he does still teach third years and postgraduates. He also It was this belief that led the This recognition of the value of loves giving lectures to the lay public Department to launch a successful bid transferring knowledge also applies to and schoolchildren, telling them the to become a Centre of Excellence in teaching within the Department with all story of the discovery of DNA Teaching and Learning, through the staff members working to translate their fingerprinting and seeing their eyes light establishment of GENIE, the first up. It is, he says, a gift of a story, Genetics CETL in the country. “Teaching delivered by academics revealing not only how science works GENIE is leading the development of but also conveying the excitement of an who are involved in leading novel approaches to teaching genetics out-of-the-blue discovery able to solve education, promoting best practice and research brings a real intellectual rapes, murders and questions of identity. the sharing of resources. GENIE has excitement to the classroom for As Sir Alec says “Teaching delivered by quickly become an integral part of the academics who are involved in leading Department both as an effective tool our students” research brings a real intellectual to continue the Department’s passion excitement to the classroom for our for disseminating an understanding of, students. At the same time teaching cutting-edge research into their and an enthusiasm for, science beyond students can challenge and shape our teaching, allowing students to benefit academia; and creating a learning research ideas. Through teaching we from developments as they occur. experience which is both innovative nurture the next generation of research and intellectually exciting. Although most of Alec Jeffreys’ time is students and scientists”. Contact details:

Department of Genetics University of Leicester Adrian Building University Road Leicester, LE1 7RH, UK t: +44 (0)116 252 3374 e: [email protected] www.le.ac.uk/genetics/

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