Research interests

Professor Jeffreys has long-standing interests in fundamental aspects of human DNA diversity and more recently in the mutational and recombinational processes that generate variation in the human genome. These interests date back to the late 1970s when he was one of the first to demonstrate human DNA variation in the form of RFLPs. His subsequent quest for highly variable regions of human DNA led to his development of DNA fingerprinting and DNA profiling methods in the mid 1980s and their implementation in forensic and legal medicine, creating the remarkable new field of forensic DNA. The minisatellites that underpin the original DNA identification systems also proved to be highly unstable in the germline, generating new length alleles at high frequency and thus driving extreme diversity into human populations. Analysis of allele structures showed the importance of aberrant meiotic recombination in driving minisatellite instability, and triggered a major programme of research into understanding more generally processes of meiotic recombination in the human genome.

Professor Jeffreys' research on genome instability involves the development of novel single DNA molecule methods to detect and characterise de novo rearrangements directly in human DNA. These powerful methods allow even very rare events to be detected and quantified. Applying this approach to meiotic recombination has allowed his team to show that most crossovers cluster into narrow hotspots that profoundly influence patterns of DNA diversity in human populations. Current research is focused on exploring the properties of hotspots, including identifying factors that determine hotspot location and activity, characterising the evolution of these surprisingly ephemeral features of the human genome, and exploring the dynamics of gene conversion within hotspots and the existence of biased conversion, a process with great potential for affecting genome evolution. His group is also extending this work to ectopic recombination between repeated DNA sequences, with particular focus on the globin gene clusters where unequal exchanges lead to a wide range of haemoglobinopathies. Key questions are the processes involved in unequal exchange and their dynamics and how these relate to levels of copy number variation seen in human populations. He is also exploring the relationship between allelic and ectopic recombination. His group also has other interests, including sex chromosome biology and exploring other modes of DNA instability in the human germline, in particular deletions and de novo base substitutions. His work closely interfaces with a broad group of researchers at Leicester exploring aspects of genome dynamics, including transposition, repeat DNA instability, telomeres, copy number variation and the monitoring of environmentally induced mutation.

Professor Jeffreys is the Royal Society Wolfson Research Professor. His work has been recognized by numerous awards including a Knighthood, the Royal Medal of the Royal Society, the Louis-Jeantet Prize for Medicine, the Albert Lasker Clinical Medical Research Award and the Dr HP Heineken Prize for Biochemistry and Biophysics. He was also voted the Morgan Stanley Great Briton 2006 and is an Honorary Freeman of the City of Leicester.

Recent Publications

Professor Jeffreys has published over 270 peer-reviewed papers, reviews, commentaries and chapters. Recent publications include:

Jeffreys AJ, Ritchie A & Neumann R. High-resolution analysis of haplotype diversity and meiotic crossover in the human TAP2 recombination hotspot. Hum. Mol. Genet . 9 725-733 (2000).

Badge RM, Yardley J, Jeffreys AJ & Armour JAL. Crossover breakpoint mapping identifies a subtelomeric hotspot for male meiotic recombination. Hum. Mol. Genet . 9 1239-1244 (2000).

Stead JDH & Jeffreys AJ. Allele diversity and germline mutation at the insulin minisatellite. Hum. Mol. Genet. 9 713-723 (2000).

Signer EN, Anzenberger G & Jeffreys AJ. Chimaeric and constitutive DNA fingerprints in the Common Marmoset ( Callithrix jacchus ).
Primates 41 49-61 (2000).

Dubrova YE, Plumb M, Gutierrez B, Boulton E & Jeffreys AJ . Transgenerational mutation by radiation. Nature 405 37 (2000).

Buard J, Collick A, Brown J & Jeffreys AJ. Somatic versus germline mutation processes at minisatellite CEB1 (D2S90) in humans and transgenic mice. Genomics 65 96-103 (2000).

Buard J, Shone AC & Jeffreys AJ. Meiotic recombination and flanking marker exchange at the highly unstable human minisatellite CEB1 (D2S90). Am. J. Hum. Genet . 67 333-344 (2000).

May CA, Tamaki K, Neumann R, Wilson G, Zagars G, Pollack A, Dubrova YE, Jeffreys AJ & Meistrich ML. Minisatellite mutation frequency in human sperm following radiotherapy. Mutat. Res. 453 67-75 (2000).

Dubrova YE, Plumb M, Brown J, Boulton E, Goodhead D & Jeffreys AJ. Induction of minisatellite mutations in the mouse germline by low-dose chronic exposure to g -radiation and fission neutrons.
Mutat. Res . 453 17-24 (2000).

Tamaki K, Brenner CH & Jeffreys AJ. Distinguishing minisatellite mutation from non-paternity by MVR-PCR. Forensic Sci. Int . 113 55-62 (2000).

Signer EN, Dubrova, YE & Jeffreys AJ. Are DNA profiles breed-specific? A pilot study in pigs. Anim. Genet . 31 273-276 (2000).

Stead JDH, Buard J, Todd JA & Jeffreys AJ. Influence of allele lineage on the role of the insulin minisatellite in susceptibility to type 1 diabetes.
Hum. Mol. Genet . 9 2929-2935 (2000).

Barber R, Plumb M, Smith AG, Cesar CE, Boulton E, Jeffreys AJ & Dubrova YE. No correlation between germline mutation at repeat DNA and meiotic crossover in male mice exposed to X-rays or cisplatin.
Mutat. Res . 457 79-91 (2000).

Jeffreys AJ. A century of human genetics: exploring variation and mutation in the human genome. In The Bicentenary Book of the Leicester Medical Society (Leicester Medical Society), pp 52-57 (2000).

Yamamoto T, Tamaki K, Huang XL, Yoshimoto T, Mizutani M, Uchihi R, Katsumata Y & Jeffreys AJ. The application of minisatellite variant repeat mapping by PCR (MVR-PCR) in a paternity case showing false exclusion due to STR mutation. J. Forensic Sci . 46 374-378 (2001).

Hollies CR, Monckton DG & Jeffreys AJ. Attempts to detect retrotransposition and de novo deletion of Alus and other dispersed repeats at specific loci in the human genome. Eur. J. Hum. Genet . 9 143-146 (2001).

Bois PRJ, Southgate L & Jeffreys AJ. Length of uninterrupted repeats determines instability at the unstable mouse expanded simple tandem repeat family MMS10 derived from independent SINE B1 elements.
Mamm. Genome 12 104-111 (2001).

Jeffreys AJ, Kauppi L & Neumann R. Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex. Nature Genet . 29 217-222 (2001).

Yauk CL, Dubrova YE, Grant GR & Jeffreys AJ. A novel single molecular analysis of spontaneous and radiation-induced mutation at a mouse tandem repeat locus. Mutat. Res . 500 147-156 (2002).

Buard J, Brenner C & Jeffreys AJ. Evolutionary fate of an unstable human minisatellite deduced from sperm-mutation spectra of individual alleles.
Am. J. Hum. Genet . 70 1038-1043 (2002).

Jeffreys AJ & Neumann R. Reciprocal crossover asymmetry and meiotic drive in a human recombination hotspot. Nature Genet . 31 267-271 (2002).

Mizukoshi T, Tamaki K, Azumi J, Matsumoto H, Immi K & Jeffreys AJ. Allelic structures at hypervariable minisatellite B6.7 in Japanese show population specificity. J. Hum. Genet . 47 232-238 (2002).

May CA, Shone AC, Kalaydjieva L, Sajantila A & Jeffreys AJ. Crossover clustering and rapid decay of linkage disequilibrium in the Xp/Yp pseudoautosomal SHOX gene. Nature Genet . 31 272-275 (2002).

Bois PRJ, Grant GR & Jeffreys AJ. Minisatellites show rare and simple intra-allelic instability in the mouse germline. Genomics 80 2-4 (2002).

Stead JDS & Jeffreys AJ. Structural analysis of insulin minisatellite alleles reveals unusually large differences in diversity between Africans and non-Africans. Am. J. Hum. Genet . 71 1273-1284 (2002).

Kauppi L, Sajantila A & Jeffreys AJ. Recombination hotspots rather than population history dominate linkage disequilibrium in the MHC class II region. Hum. Mol. Genet . 12 33-44 (2003).

Yauk CL, Bois PRJ & Jeffreys AJ. High-resolution sperm typing of meiotic recombination in the mouse MHC E ß gene. EMBO J . 22 1389-1397 (2003).

Berg I, Neumann R, Cederberg H, Rannug U & Jeffreys AJ. Two modes of germline instability at human minisatellite MS1 (locus D1S7 ): complex rearrangements and paradoxical hyperdeletion. Am. J. Hum. Genet. 72 1436-1447 (2003).

Stead JDH, Hurles ME & Jeffreys AJ. Global haplotype diversity in the human insulin gene region. Genome Res , 13 2101-2111 (2003).

Jeffreys AJ, Holloway JK, Kauppi L, May CA, Neumann R, Slingsby MT & Webb AJ. Meiotic recombination hot spots and human DNA diversity. Phil. Trans. R. Soc. Lond. B 359 141-152 (2004).

Jeffreys AJ & May CA. DNA enrichment by allele-specific hybridization (DEASH): A novel method for haplotyping and for detecting low-frequency base substitutional variants and recombinant DNA molecules.
Genome Res. 13 2316-2324 (2003).

Jeffreys AJ. Genetic fingerprinting. In DNA Changing Science and Society, ed. Krude T, Cambridge University Press, pp44-67 (2004).

Jeffreys AJ & May CA. Intense and highly localized gene conversion activity in human meiotic crossover hot spots. Nature Genetics 36 151-156, (2004).

Kauppi L, Jeffreys AJ & Keeney S. Where the crossovers are: Recombination distributions in mammals. Nature Rev. Genet. 5 413-424 (2004).

Kauppi L, Stumpf MPH & Jeffreys AJ. Localized breakdown in linkage disequilibrium does not always predict sperm crossover hotspots in the human MHC class II region. Genomics 86 13-24 (2005).

Jeffreys AJ, Neumann R, Panayi M, Myers S & Donnelly P. Human recombination hot spots hidden within regions of strong marker association. Nature Genet . 37 601-606 (2005).

Jeyapalan JN, Varley H, Foxon JL, Pollock RE, Jeffreys AJ, Henson JD, Reddel RR & Royle NJ. Activation of the ALT pathway for telomere maintenance can affect other sequences in the human genome.
Hum. Mol. Genet . 14 1785-1794 (2005).

Jeffreys AJ & Neumann R. Factors influencing recombination frequency and distribution in a human meiotic crossover hotspot. Hum. Mol. Genet . 14 2277-2287 (2005).

Tamaki K & Jeffreys AJ. Human tandem repeat sequences in forensic DNA typing. Legal Medicine 7 244-250 (2005).

Jeffreys AJ. Genetic fingerprinting. Nature Med . 11 1035-1039 (2005).

Holloway K, Lawson VE & Jeffreys AJ. Allelic recombination and de novo deletions in sperm in the human b -globin gene region.
Hum. Mol. Genet .15, 1099-1111 (2006).

Neumann R. & Jeffreys AJ Polymorphism in the activity of human crossover hotspots independent of local DNA sequence variation. Hum. Mol. Genet . 15 1401-1411 (2006).

Lam KWG & Jeffreys AJ Processes of copy number change in human DNA : The dynamics of a -globin gene deletion. Proc. Natl. Acad. Sci. USA 103 8921-8927 (2006).

Lam KWG & Jeffreys AJ. Processes of de novo duplication of human a -globin genes. Proc. Natl. Acad. Sci. USA. 104 10950-10955 (2007).

Bonhomme F, Rivals E, Orth A, Grant GR, Jeffreys AJ & Bois PR. Species-wide distribution of highly polymorphic minisatellite markers suggests past and present genetic exchanges among house mouse subspecies.
Genome Biol. 8 R80 (2007).

May CA, Slingsby MT & Jeffreys AJ. Human recombination hotspots before and after the HapMap project. In Genome Dynamics & Stability 2: Recombination and Meiosis . ed. Egel R & Lankenau D-H (Springer-Verlag), pp 195-244 (2008).

Webb AJ, Berg IL, & Jeffreys AJ. Sperm crossover activity in regions of the human genome showing extreme breakdown of marker association.
Proc. Natl. Acad. Sci. USA. 105 10271-10632 (2008).

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