Genetic “fingerprinting”

The invention: Atechnique for using the unique characteristics of
each human being’s DNA to identify individuals, establish connections
among relatives, and identify criminals.
The people behind the invention:
Alec Jeffreys (1950- ), an English geneticist
Victoria Wilson (1950- ), an English geneticist
Swee Lay Thein (1951- ), a biochemical geneticist
Microscopic Fingerprints
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 genetic
structure. Jeffreys’s 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 (indicating
only whether a suspect could or could not be the perpetrator of a
crime), DNA fingerprinting provides positive identification.
For example, under favorable conditions, the technique can establish
with virtual certainty whether a given individual is a murderer
or rapist. The applications 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 for mapping disease-causing genes on chromosomes. In
addition, the technique is utilized by animal geneticists to establish
paternity and to detect genetic relatedness between social groups.
DNAfingerprinting (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, doublestranded
molecule composed of four different units called “bases.”
The bases on one strand of DNApair with complementary bases on the other strand. A human being contains twenty-three pairs of
chromosomes; one member of each chromosome pair is inherited
fromthe mother, the other fromthe father. The order, or sequence, of
bases forms the genetic message, which is 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
split DNA into fragments that could be analyzed. This situation
changed with the advent of biotechnology in the mid-1970’s.
The door toDNAanalysis 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 splits the DNAat 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 exposed to a radioactive DNA probe, which can bind to
specific complementary DNA sequences in the fragments. X-ray
film detects the radioactive pattern. The developed film, called an
“autoradiograph,” shows a pattern of DNA fragments, which is
similar to a bar code and can be compared with patterns from
known subjects.
The Presence of Minisatellites
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.
In 1985, Jeffreys and his coworkers, Victoria Wilson at the University
of Leicester and Swee Lay Thein at the John Radcliffe Hospital
in Oxford, discovered a way to produce a DNA fingerprint.
Jeffreys had found previously that human DNA contains many repeated
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 using two labeled DNA 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. As Jeffreys discovered,
the likelihood of two unrelated people having completely
identical DNAfingerprints is extremely small—less than one in ten
trillion. Given the population of the world, it is clear that the technique
can distinguish any one person from everyone else. Jeffreys
called his band patterns “DNAfingerprints” 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.”
Consequences
In addition to being used in human identification, DNA fingerprinting
has found applications in medical genetics. In the search
for a cause, a diagnostic test for, and ultimately the treatment of an
inherited disease, it is necessary to locate the defective gene on a human
chromosome. Gene location is accomplished by 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 provide a potent and valuable set of markers that are 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.
Genetic fingerprinting also has had a major impact on genetic
studies of higher animals. BecauseDNAsequences 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; this made it possible for him to produce DNA fingerprints of
these vertebrates. In addition, the technique has been used to discern
the mating behavior of birds, to determine paternity in zoo primates,
and to detect inbreeding in imperiled wildlife. DNA fingerprinting
can also be applied to animal breeding problems, such as
the identification of stolen animals, the verification of semen samples
for artificial insemination, and the determination of pedigree.
The technique is not foolproof, however, and results may be far
from ideal. Especially in the area of forensic science, there was a
rush to use the tremendous power of DNA fingerprinting to identify
a purported murderer or rapist, and the need for scientific standards
was often neglected. Some problems arose because forensic
DNA fingerprinting in the United States is generally conducted in
private, unregulated laboratories. In the absence of rigorous scientific
controls, the DNA fingerprint bands of two completely unknown
samples cannot be matched precisely, and the results may be
unreliable.