Human Molecular Genetics, 2000, Vol. 9, No. 5 725-733
© 2000 Oxford University Press
High resolution analysis of haplotype diversity and meiotic crossover in the human TAP2 recombination hotspot
Department of Genetics, University of Leicester, Leicester LE1 7RH, UK
Little is known about the nature of recombination hotspots in the human genome and the relationship between crossover activity and patterns of linkage disequilibrium. We have therefore used both haplotype analysis and direct detection of crossovers in sperm to characterize a putative recombination hotspot in the TAP2 gene within the class II region of the MHC. Haplotype diversity provided evidence for a localized hotspot within intron 2 of this gene. Sperm DNA typing using allele-specific PCR primers to selectively amplify recombinant TAP2 molecules revealed a highly localized meiotic crossover hotspot ~1.2 kb long, unusually abundant in sequence polymorphisms and flanked by DNA much less active in recombination. Sperm crossover appeared to be fully reciprocal, and almost all crossover products were simple, involving a single exchange between adjacent heterozygous markers. This hotspot appears to be much more active in female than male meiosis. No primary sequence similarities could be found between any of the very few well defined crossover hotspots in the human genome, all of which show recombinationally active domains 1–2 kb long. Direct comparison of recombination frequency and haplotype diversity in TAP2 showed that linkage disequilibrium measures were a poor predictor of crossover frequency in this region, with non-recombining markers sometimes in free association and with examples of pairs of markers spanning the recombination hotspot showing substantial or even absolute linkage disequilibrium.
+ To whom correspondence should be addressed. Tel: +44 116 252 3435; Fax: +44 116 252 3378; Email: ajj@le.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. J. Webb, I. L. Berg, and A. Jeffreys Sperm cross-over activity in regions of the human genome showing extreme breakdown of marker association PNAS, July 29, 2008; 105(30): 10471 - 10476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. J. Bois A Highly Polymorphic Meiotic Recombination Mouse Hot Spot Exhibits Incomplete Repair Mol. Cell. Biol., October 15, 2007; 27(20): 7053 - 7062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kauppi, M. Jasin, and S. Keeney Meiotic crossover hotspots contained in haplotype block boundaries of the mouse genome PNAS, August 14, 2007; 104(33): 13396 - 13401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-W. G. Lam and A. J. Jeffreys Processes of de novo duplication of human {alpha}-globin genes PNAS, June 26, 2007; 104(26): 10950 - 10955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Baumber, C. Sjostrand, M. Leone, H. Harty, G. Bussone, J. Hillert, R. C. Trembath, and M. B. Russell A genome-wide scan and HCRTR2 candidate gene analysis in a European cluster headache cohort Neurology, June 27, 2006; 66(12): 1888 - 1893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-W. G. Lam and A. J. Jeffreys Inaugural Article: Processes of copy-number change in human DNA: The dynamics of {alpha}-globin gene deletion PNAS, June 13, 2006; 103(24): 8921 - 8927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Neumann and A. J. Jeffreys Polymorphism in the activity of human crossover hotspots independent of local DNA sequence variation Hum. Mol. Genet., May 1, 2006; 15(9): 1401 - 1411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Aly, E. Eller, A. Ide, K. Gowan, S. R. Babu, H. A. Erlich, M. J. Rewers, G. S. Eisenbarth, and P. R. Fain Multi-SNP Analysis of MHC Region: Remarkable Conservation of HLA-A1-B8-DR3 Haplotype. Diabetes, May 1, 2006; 55(5): 1265 - 1269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Holloway, V. E. Lawson, and A. J. Jeffreys Allelic recombination and de novo deletions in sperm in the human {beta}-globin gene region Hum. Mol. Genet., April 1, 2006; 15(7): 1099 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Greenspan and D. Geiger Modeling Haplotype Block Variation Using Markov Chains Genetics, April 1, 2006; 172(4): 2583 - 2599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Greenawalt, X. Cui, Y. Wu, Y. Lin, H.-Y. Wang, M. Luo, I. V. Tereshchenko, G. Hu, J. Y. Li, Y. Chu, et al. Strong correlation between meiotic crossovers and haplotype structure in a 2.5-Mb region on the long arm of chromosome 21 Genome Res., February 1, 2006; 16(2): 208 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Jeffreys and R. Neumann Factors influencing recombination frequency and distribution in a human meiotic crossover hotspot Hum. Mol. Genet., August 1, 2005; 14(15): 2277 - 2287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Jiang, X. Zhang, R. Deka, and L. Jin Genome amplification of single sperm using multiple displacement amplification Nucleic Acids Res., June 7, 2005; 33(10): e91 - e91. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yi and W.-H. Li Molecular Evolution of Recombination Hotspots and Highly Recombining Pseudoautosomal Regions in Hominoids Mol. Biol. Evol., May 1, 2005; 22(5): 1223 - 1230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Winckler, S. R. Myers, D. J. Richter, R. C. Onofrio, G. J. McDonald, R. E. Bontrop, G. A. T. McVean, S. B. Gabriel, D. Reich, P. Donnelly, et al. Comparison of Fine-Scale Recombination Rates in Humans and Chimpanzees Science, April 1, 2005; 308(5718): 107 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Sambrook, A. Bashirova, S. Palmer, S. Sims, J. Trowsdale, L. Abi-Rached, P. Parham, M. Carrington, and S. Beck Single haplotype analysis demonstrates rapid evolution of the killer immunoglobulin-like receptor (KIR) loci in primates Genome Res., January 1, 2005; 15(1): 25 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Rana, N. D. Ebenezer, A. R. Webster, A. R. Linares, D. B. Whitehouse, S. Povey, and A. J. Hardcastle Recombination hotspots and block structure of linkage disequilibrium in the human genome exemplified by detailed analysis of PGM1 on 1p31 Hum. Mol. Genet., December 15, 2004; 13(24): 3089 - 3102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, F. Li, J. Li, M. Q. Zhang, and X. Zhang Evidence and characteristics of putative human {alpha} recombination hotspots Hum. Mol. Genet., November 15, 2004; 13(22): 2823 - 2828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Fearnhead, R. M. Harding, J. A. Schneider, S. Myers, and P. Donnelly Application of Coalescent Methods to Reveal Fine-Scale Rate Variation and Recombination Hotspots Genetics, August 1, 2004; 167(4): 2067 - 2081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Nishant, H. Ravishankar, and M. R. S. Rao Characterization of a Mouse Recombination Hot Spot Locus Encoding a Novel Non-Protein-Coding RNA Mol. Cell. Biol., June 15, 2004; 24(12): 5620 - 5634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Knoblauch, A. Bauerfeind, M. R. Toliat, C. Becker, T. Luganskaja, U. P. Gunther, K. Rohde, H. Schuster, C. Junghans, F. C. Luft, et al. Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol Hum. Mol. Genet., May 15, 2004; 13(10): 993 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Ptak, K. Voelpel, and M. Przeworski Insights Into Recombination From Patterns of Linkage Disequilibrium in Humans Genetics, May 1, 2004; 167(1): 387 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. T. McVean, S. R. Myers, S. Hunt, P. Deloukas, D. R. Bentley, and P. Donnelly The Fine-Scale Structure of Recombination Rate Variation in the Human Genome Science, April 23, 2004; 304(5670): 581 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Ke, S. Hunt, W. Tapper, R. Lawrence, G. Stavrides, J. Ghori, P. Whittaker, A. Collins, A. P. Morris, D. Bentley, et al. The impact of SNP density on fine-scale patterns of linkage disequilibrium Hum. Mol. Genet., March 15, 2004; 13(6): 577 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Schulze, K. Zhang, Y.-S. Chen, N. Akula, F. Sun, and F. J. McMahon Defining haplotype blocks and tag single-nucleotide polymorphisms in the human genome Hum. Mol. Genet., February 1, 2004; 13(3): 335 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Li and M. Stephens Modeling Linkage Disequilibrium and Identifying Recombination Hotspots Using Single-Nucleotide Polymorphism Data Genetics, December 1, 2003; 165(4): 2213 - 2233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Jeffreys and C. A. May 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., October 1, 2003; 13(10): 2316 - 2324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Capon, I K Toal, J C Evans, M H Allen, S Patel, D Tillman, D Burden, J N W N Barker, and R C Trembath Haplotype analysis of distantly related populations implicates corneodesmosin in psoriasis susceptibility J. Med. Genet., June 1, 2003; 40(6): 447 - 452. [Full Text] [PDF]
|
|
|
|
|
|
L. Kauppi, A. Sajantila, and A. J. Jeffreys Recombination hotspots rather than population history dominate linkage disequilibrium in the MHC class II region Hum. Mol. Genet., January 1, 2003; 12(1): 33 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. U. Koelsch, A. Kindler-Rohrborn, S. Held, S. Zabel, and M. F. Rajewsky Loss of heterozygosity in malignant rat schwannomas chemically induced in hybrids of inbred rat strains with differential tumor susceptibility Carcinogenesis, June 1, 2002; 23(6): 1033 - 1037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Asumalahti, C. Veal, T. Laitinen, S. Suomela, M. Allen, O. Elomaa, M. Moser, R. de Cid, S. Ripatti, I. Vorechovsky, et al. Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus Hum. Mol. Genet., March 1, 2002; 11(5): 589 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Schneider, T. E. A. Peto, R. A. Boone, A. J. Boyce, and J. B. Clegg Direct measurement of the male recombination fraction in the human {beta}-globin hot spot Hum. Mol. Genet., February 1, 2002; 11(3): 207 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Marrosu, R. Murru, M. R. Murru, G. Costa, P. Zavattari, M. Whalen, E. Cocco, C. Mancosu, L. Schirru, E. Solla, et al. Dissection of the HLA association with multiple sclerosis in the founder isolated population of Sardinia Hum. Mol. Genet., December 1, 2001; 10(25): 2907 - 2916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. F. Abdullah and R. H. Borts Meiotic recombination frequencies are affected by nutritional states in Saccharomycescerevisiae PNAS, November 20, 2001; (2001) 201529598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Eisenbarth, A. M. Striebel, E. Moschgath, W. Vogel, and G. Assum Long-range sequence composition mirrors linkage disequilibrium pattern in a 1.13 Mb region of human chromosome 22 Hum. Mol. Genet., November 1, 2001; 10(24): 2833 - 2839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Zavattari, E. Deidda, M. Whalen, R. Lampis, A. Mulargia, M. Loddo, I. Eaves, G. Mastio, J. A. Todd, and F. Cucca Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography, chromosome recombination frequency and selection Hum. Mol. Genet., December 1, 2000; 9(20): 2947 - 2957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Zavattari, R. Lampis, A. Mulargia, M. Loddo, E. Angius, J. A. Todd, and F. Cucca Confirmation of the DRB1-DQB1 loci as the major component of IDDM1 in the isolated founder population of Sardinia Hum. Mol. Genet., December 1, 2000; 9(20): 2967 - 2972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. C. Gray, D. A. Campbell, and N. K. Spurr Single nucleotide polymorphisms as tools in human genetics Hum. Mol. Genet., October 1, 2000; 9(16): 2403 - 2408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Badge, J. Yardley, A. J. Jeffreys, and J. A. L. Armour Crossover breakpoint mapping identifies a subtelomeric hotspot for male meiotic recombination Hum. Mol. Genet., May 1, 2000; 9(8): 1239 - 1244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. F. Abdullah and R. H. Borts Meiotic recombination frequencies are affected by nutritional states in Saccharomycescerevisiae PNAS, December 4, 2001; 98(25): 14524 - 14529. [Abstract] [Full Text] [PDF]
|
|