Sir Alec Jeffreys

Sir Alec Jeffreys is renowned for his development of the first DNA fingerprinting techniques. He was initially working in Amsterdam with Dick Flavell, establishing how to detect single copies of human genes. In 1977, Jeffreys moved to Leicester, where he began using molecular biology techniques in the investigation of human genetics, using primitive gene detection methods to study gene structures and inherited variation. His work resulted in the first description of Restriction Fragment Length Polymorphism (RFLP), a technique which involved the use of enzymes to target short DNA sequences and cut the genome into pieces.

In 1978, Jeffreys first described single nucleotide polymorphism (SNP). SNPs are DNA sequence variations which occur when a single nucleotide differs between members of a species or between the paired chromosomes in a person. When a SNP site is present at the target site, the enzyme is prevented from cutting the DNA at that site. However SNPs did not show great variation, and so Jeffreys began looking for sections of DNA with more significant variation.

Jeffreys focused on tandem repeat DNA, however these were at first difficult to locate in the human genome. The breakthrough came through a different project investigating the myoglobin gene in humans, a gene first found in grey seals. This was used to isolate the corresponding gene in humans, which was found inside a minisatellite. This myoglobin minisatellite was then used to identify further minisatellites until a core sequence was found. This was a DNA piece similar in numerous minisatellites.

A probe was produced through core sequencing that should hybridise to numerous minisatellites simultaneously. This probe was hybridised to a blot with DNA from his research assistant Jenny Foxon and her parents. In 1984, an X-ray blot was developed. This was initially viewed as nothing more than a complex mess, but soon patterns emerged, expressing individual specificity. Jeffreys realised that this was the first DNA fingerprint. Over time the image was improved and more variable minisatellites were discovered and targeted. However there were significant difficulties with Jeffreys’ method in that large sample sizes were required and the technique could not be automated. This led to DNA profiling gradually becoming more sensitive, reproducible and suitable to computer databasing, allowing DNA databases to eventually be created. Improvements include being combined with PCR in 1989, the use of STRs in 1990, and the incorporation of DNA profiles with databases.

 

Cherfas, Jeremy. Geneticists Develop DNA Fingerprinting. New Scientist. 1985, 28th March, 21.

Grody, W W. Kiechle, F L. Nakamura, R M. Strom, C., YEAR. Molecular Diagnostics: Techniques and Applications for the Clinical Laboratory. London: Elsevier.