With his production of “fingerprints” of human DNA that are completely specific to individuals, Alec Jeffreys made a major impact on problems related to human identification, such as establishing family relationships and identifying criminals.
In 1985, Alec Jeffreys, a geneticist at the University of Leicester in England, developed a method of deoxyribonucleic acid (DNA) analysis that provides a visual representation of the human genome. Jeffreys’ discovery had an immediate, revolutionary impact on problems of human identification, especially the identification of criminals. Whereas earlier techniques, such as conventional blood typing, provide evidence that is merely exclusionary, DNA fingerprinting provides positive identification. Under favorable conditions, the technique can establish identity with virtual certainty. The applications of the technique are not limited to forensic science; DNA fingerprinting can also establish definitive proof of parenthood (paternity or maternity), and it is invaluable in providing markers to map disease-causing genes on chromosomes. In addition, animal geneticists use the technique to establish paternity and to detect genetic relatedness between social groups.
DNA fingerprinting (also referred to as genetic fingerprinting) is a sophisticated technique that must be executed carefully to produce valid results. The technical difficulties arise partly from the complex nature of DNA. DNA, the genetic material responsible for heredity in all higher forms of life, is an enormously long, double-stranded polymeric molecule composed of four different units called bases. The bases on one strand of DNA pair with complementary bases on the other strand. A human being contains twenty-three pairs of chromosomes; one member of each chromosome pair is inherited from the mother, the other from the father. Each chromosome has a continuous stretch of double-stranded DNA containing 50 million to 500 million base pairs. The order, or sequence, of bases forms the genetic message, called the genome. Scientists did not know the sequence of bases in any sizable stretch of DNA prior to the 1970’s because they lacked the molecular tools to cleave DNA into fragments that could be analyzed. This situation changed with the advent of biotechnology in the mid-1970’s.
The door to DNA analysis was opened with the discovery of bacterial enzymes called DNA restriction enzymes. A restriction enzyme binds to DNA whenever it finds a specific short sequence of base pairs (analogous to a code word), and it cleaves DNA at a defined site within that sequence. A single enzyme finds millions of cutting sites in human DNA, and the resulting fragments range in size from tens of base pairs to hundreds or thousands. The fragments are separated in order of their length by a process called gel electrophoresis, in which an electrical field separates smaller and larger DNA fragments on a porous gel. Fragment size can be estimated by comparing the position in a gel of a fragment with that of marker DNA pieces of known size. The fragments are transferred from the gel to a membrane filter, where they are exposed to a radioactive DNA probe, which can bind to specific complementary DNA sequences in the fragments. X-ray film sandwiched to the membrane detects the radioactive pattern. The developed film, called an autoradiograph,
The uniqueness of a DNA fingerprint depends on the fact that, with the exception of identical twins, no two human beings have identical DNA sequences. Of the three billion base pairs in human DNA, many will differ from one person to another. Many of these sequence variations result from base-pair changes that create or destroy a cleavage site for a restriction enzyme and thereby cause variation in fragment length from one individual to the next. The variation can be detected through the use of labeled probe DNA sequences that are complementary to sequences located near restriction cutting sites. This type of probe reveals whether a certain cleavage site is present or absent in a given sample of DNA. Because cleavage sites are either present or absent, however, this type of probe is only moderately sensitive, and the resulting fragment band pattern, or autoradiograph, will not be absolutely unique for an individual.
Alec Jeffreys.
In 1985, Jeffreys and two colleagues, Victoria Wilson at the University of Leicester and Swee Lay Thein at the John Radcliffe Hospital in Oxford, discovered a vastly more powerful type of probe, powerful enough to produce a DNA fingerprint. Jeffreys had found previously that human DNA contains many multirepeated minisequences called minisatellites. Minisatellites consist of sequences of base pairs repeated in tandem, and the number of repeated units varies widely from one individual to another. Every person, with the exception of identical twins, has a different number of tandem repeats and, hence, different lengths of minisatellite DNA. By virtue of this difference, DNA fragments, which vary in length correspondingly, can be generated through the cleaving of DNA at a restriction site close to minisatellite DNA. The complexity of minisatellite DNA and the multiple repeat options of the tandem sequences enable probes to minisatellites to be very sensitive in differentiating one person from another. By the use of two labeled probes to detect two different minisatellite sequences, Jeffreys obtained a unique fragment band pattern that was completely specific for an individual.
The power of the technique derives from the law of chance, which indicates that the probability (chance) that two or more unrelated events will occur simultaneously is calculated as the multiplication product of the two separate probabilities. Jeffreys used two different probes to produce autoradiographs, which contained a total of thirty-six significant bands. He calculated that the probability of two unrelated people having an identical band was one in four, or one-fourth; hence the chance of two people having thirty-six identical bands is the fraction one-fourth multiplied by itself thirty-six times. The resulting fraction is extremely small less than one in ten trillion. Given the population of the world, it is obvious that the technique can distinguish a person from anyone else in the universe.
Jeffreys called his band patterns DNA fingerprints because of their ability to individualize. As he stated in his landmark research paper, published in the English scientific journal Nature in 1985, probes to minisatellite regions of human DNA produce “DNA ’fingerprints’ which are completely specific to an individual (or to his or her identical twin) and can be applied directly to problems of human identification, including parenthood testing.”
The impact of genetic fingerprinting was immediate and broad-ranging. Genetic fingerprinting provides a powerful method for establishing family relationships in paternity (and occasionally maternity) disputes. It allows parenthood to be established with an extremely high level of certainty, vastly greater than that obtained using conventional genetic marker tests. Using DNA fingerprints, scientists can establish whether a purported child-parent relationship is actual by testing whether all of the child’s DNA fragments are present in the claimed mother’s and/or father’s DNA fingerprint. The method was used within a few months of its discovery in an English immigration dispute to prove that a boy from Ghana was the son, and not the nephew or other close relative, of a Ghanaian woman living in England.
The technique had revolutionary effects on forensic science
DNA fingerprinting also found wide application in the field of medical genetics. In the search for a cause, diagnostic test, and ultimately treatment of an inherited disease, it is necessary to locate the defective gene on a human chromosome. Gene location is accomplished through a technique called linkage analysis, in which geneticists use marker sections of DNA as reference points to pinpoint the position of a defective gene on a chromosome. The minisatellite DNA probes developed by Jeffreys provided a potent and valuable set of markers that geneticists found to be of great value in locating disease-causing genes. Soon after its discovery, DNA fingerprinting was used to locate the defective genes responsible for several diseases, including fetal hemoglobin abnormality and Huntington’s disease.
In addition to its other applications, genetic fingerprinting had a major impact on genetic studies of higher animals. Because DNA sequences are conserved in evolution, humans and other vertebrates have many sequences in common. This commonality enabled Jeffreys to use his probes to human minisatellites to bind to the DNA of many different vertebrates, ranging from mammals to birds, reptiles, amphibians, and fish; he thereby produced DNA fingerprints of these vertebrates. In addition, the technique has been used to discern the mating behaviors of birds, to determine paternity in zoo primates, and to detect inbreeding in imperiled wildlife. DNA fingerprinting has also been applied to problems encountered by animal breeders, such as the identification of stolen animals, the verification of semen samples for artificial insemination, and the determination of pedigree.
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Jeffreys, Alec J. “High Variable Minisatellites and DNA Fingerprints.” Biochemical Society Transactions 15, no. 3 (1987): 309-317. Provides a comprehensive discussion of DNA fingerprinting and its applications. Intended for scientifically knowledgeable readers. -
Jeffreys, Alec J., Victoria Wilson, and Swee Lay Thein. “Individual-Specific ’Fingerprints’ of Human DNA.” Nature 316 (July 4, 1985): 76-79. Describes the fundamental work of Jeffreys and his coworkers in precise, technical language. Intended for readers with background in genetics or biochemistry. -
Lewin, Roger. “DNA Fingerprints in Health and Disease.” Science 223 (August 1, 1986): 521-522. Explains in nontechnical terms the scientific background of Jeffreys’ technique and its various applications to forensic science, to establishing parenthood, and to mapping the location of defective, disease-causing genes on human chromosomes. -
_______. “Limits to DNA Fingerprinting.” Science 243 (March 14, 1989): 1549-1551. Discusses limitations in the application of DNA fingerprinting to animal behavior research. -
Marx, Jean L. “DNA Fingerprinting Takes the Witness Stand.” Science 240 (June 17, 1988): 1616-1618. Scientific news article discusses the technique of DNA fingerprinting and its application to the identification of murderers and rapists. Written in nontechnical language. -
Neufeld, Peter J., and Neville Colman. “When Science Takes the Witness Stand.” Scientific American 262 (May, 1990): 46-53. Addresses the problems associated with admitting forensic testimony (including DNA fingerprinting) into criminal cases. Aimed at general readers. -
Thompson, William C., and Simon Ford. “Is DNA Fingerprinting Ready for the Courts?” New Scientist 125 (March 31, 1990): 38-43. Discusses the scientific background of DNA fingerprinting and problems associated with the interpretation of forensic evidence. Aimed at general readers. -
White, Ray, and Jean-Marc Lalouel. “Chromosome Mapping with DNA Markers.” Scientific American 258 (February, 1988): 40-48. General science article discusses the use of DNA markers, including Jeffreys’ markers, to map chromosomes and trace defective genes. -
Zonderman, Jon. Beyond the Crime Lab: The New Science of Investigation. Rev. ed. New York: John Wiley & Sons, 1999. Examines the advances that have been made in the methods used by criminal forensics experts. Chapter 5 is devoted to discussion of the use of DNA for identification.
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