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Comparison of fine-scale recombination rates in humans and chimpanzees
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The authors inferred rates of crossover from resequencing polymorphism data at orthologous loci in western chimpanzees and in CEPH and Yoruban HapMap ENCODE regions. They found statistical support for 18 hotspots in humans and 3 in chimps (ρ < 0.01), but with a striking lack of overlap: a crossover hotspot in one species was typically found to have crossover rate 10 to 60 times larger than that of the same region of the other species, which was typically not 'hot' at all relative to its background crossover rates.
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Winckler W., Myers S.R., Richter D.J., Onofrio R.C., McDonald G.J., Bontrop R.E., McVean G.A., Gabriel S.B., Reich D., Donnelly P., and Altshuler D. Comparison of fine-scale recombination rates in humans and chimpanzees. Science 308 (2005) 107-111. The authors inferred rates of crossover from resequencing polymorphism data at orthologous loci in western chimpanzees and in CEPH and Yoruban HapMap ENCODE regions. They found statistical support for 18 hotspots in humans and 3 in chimps (ρ < 0.01), but with a striking lack of overlap: a crossover hotspot in one species was typically found to have crossover rate 10 to 60 times larger than that of the same region of the other species, which was typically not 'hot' at all relative to its background crossover rates.
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(2005)
Science
, vol.308
, pp. 107-111
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Winckler, W.1
Myers, S.R.2
Richter, D.J.3
Onofrio, R.C.4
McDonald, G.J.5
Bontrop, R.E.6
McVean, G.A.7
Gabriel, S.B.8
Reich, D.9
Donnelly, P.10
Altshuler, D.11
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38
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20044377420
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Human recombination hot spots hidden in regions of strong marker association
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e = 10000), which they compare against that found by sperm analysis. In three of the hotspots, the estimated values from LD analysis were significantly different (e.g. r for NID2a was estimated as 55 cM/Mb from LD analysis, compared with 10 cM/Mb from sperm analysis).
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e = 10000), which they compare against that found by sperm analysis. In three of the hotspots, the estimated values from LD analysis were significantly different (e.g. r for NID2a was estimated as 55 cM/Mb from LD analysis, compared with 10 cM/Mb from sperm analysis).
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(2005)
Nat Genet
, vol.37
, pp. 601-606
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Jeffreys, A.J.1
Neumann, R.2
Panayi, M.3
Myers, S.4
Donnelly, P.5
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39
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33646948896
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High-resolution recombination patterns in a region of human chromosome 21 measured by sperm typing
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The authors examine crossover activity across a 103 kb segment of chromosome 21, using the sperm of 240 individuals. They find two hotspots in this region, each of width of 1-2 kb, and estimate that 71% of the total crossover activity occurs in ∼12% of the sequence. They find that the patterns of estimated crossover activity from sperm analysis correspond well to those of various LD methods. Furthermore, studying one of the hotspots in more fine-scale detail in three men showed that the majority of the crossover activity for two of the men mapped to one ∼2 kb interval, whereas in the third man the majority of activity mapped to an apparently distinct region ∼2 kb away. The authors speculate that when one hotspot dies away, a new hotspot arises relatively nearby.
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Tiemann-Boege I., Calabrese P., Cochran D.M., Sokol R., and Arnheim N. High-resolution recombination patterns in a region of human chromosome 21 measured by sperm typing. PLoS Genet 2 (2006) e70. The authors examine crossover activity across a 103 kb segment of chromosome 21, using the sperm of 240 individuals. They find two hotspots in this region, each of width of 1-2 kb, and estimate that 71% of the total crossover activity occurs in ∼12% of the sequence. They find that the patterns of estimated crossover activity from sperm analysis correspond well to those of various LD methods. Furthermore, studying one of the hotspots in more fine-scale detail in three men showed that the majority of the crossover activity for two of the men mapped to one ∼2 kb interval, whereas in the third man the majority of activity mapped to an apparently distinct region ∼2 kb away. The authors speculate that when one hotspot dies away, a new hotspot arises relatively nearby.
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(2006)
PLoS Genet
, vol.2
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Tiemann-Boege, I.1
Calabrese, P.2
Cochran, D.M.3
Sokol, R.4
Arnheim, N.5
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40
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0842310835
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Intense and highly localized gene conversion activity in human meiotic crossover hot spots
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The authors examine the DNA3 crossover hotspot of the human MHC by sperm analysis of two men, finding DNA3 to be a hotspot for gene conversion as well; they speculate that DNA3 is a hotspot for double-strand-breaks overall. They find that gene conversions occur 4-15 times more often than crossovers in the two men studied. They estimate tract length to be, on average, 55-290 bp per gene conversion event, and note that tracts for conversion accompanying crossover appear to be somewhat larger (∼460 bp).
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Jeffreys A.J., and May C.A. Intense and highly localized gene conversion activity in human meiotic crossover hot spots. Nat Genet 36 (2004) 151-156. The authors examine the DNA3 crossover hotspot of the human MHC by sperm analysis of two men, finding DNA3 to be a hotspot for gene conversion as well; they speculate that DNA3 is a hotspot for double-strand-breaks overall. They find that gene conversions occur 4-15 times more often than crossovers in the two men studied. They estimate tract length to be, on average, 55-290 bp per gene conversion event, and note that tracts for conversion accompanying crossover appear to be somewhat larger (∼460 bp).
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(2004)
Nat Genet
, vol.36
, pp. 151-156
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Jeffreys, A.J.1
May, C.A.2
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41
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33645127519
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Allelic recombination and de novo deletions in sperm in the human β-globin gene region
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The authors use sperm analysis to characterize the crossover activity of 13.5 kb of sequence in the β-globin gene region. Using two donors, they find an intense, narrow crossover hotspot, ∼1.2 kb wide, with crossover activity of ∼150-260 cM/Mb. Examining the hotspot of one of these men for gene conversion alone, however, detected no gene conversions. This finding does not appear to be attributable to lack of power or marker density. The authors conclude that the relative rate of gene conversion to crossover in this region must be <1/12. Furthermore, they do not find any evidence of association between deletion breakpoints and high crossover activity.
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Holloway K., Lawson V.E., and Jeffreys A.J. Allelic recombination and de novo deletions in sperm in the human β-globin gene region. Hum Mol Genet 17 (2006) 1099-1111. The authors use sperm analysis to characterize the crossover activity of 13.5 kb of sequence in the β-globin gene region. Using two donors, they find an intense, narrow crossover hotspot, ∼1.2 kb wide, with crossover activity of ∼150-260 cM/Mb. Examining the hotspot of one of these men for gene conversion alone, however, detected no gene conversions. This finding does not appear to be attributable to lack of power or marker density. The authors conclude that the relative rate of gene conversion to crossover in this region must be <1/12. Furthermore, they do not find any evidence of association between deletion breakpoints and high crossover activity.
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(2006)
Hum Mol Genet
, vol.17
, pp. 1099-1111
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Holloway, K.1
Lawson, V.E.2
Jeffreys, A.J.3
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43
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0034892915
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Lower-than-expected linkage disequilibrium between tightly linked markers in humans suggests a role for gene conversion
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Ardlie K., Liu-Cordero S.N., Eberle M.A., Daly M., Barrett J., Winchester E., Lander E.S., and Kruglyak L. Lower-than-expected linkage disequilibrium between tightly linked markers in humans suggests a role for gene conversion. Am J Hum Genet 69 (2001) 582-589
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(2001)
Am J Hum Genet
, vol.69
, pp. 582-589
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Ardlie, K.1
Liu-Cordero, S.N.2
Eberle, M.A.3
Daly, M.4
Barrett, J.5
Winchester, E.6
Lander, E.S.7
Kruglyak, L.8
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44
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4143054668
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Estimating the rate of gene conversion on human chromosome 21
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Using simple multilocus summary statistics, the authors estimate rates of gene conversion and crossover in humans. The rates are based on patterns of LD, using the DNA from a worldwide sample of 20 chromosomes representing a 28 Mb region of chromosome 21. They estimate f to be ∼1.6, assuming a tract length of 500 bp. Estimating rates over overlapping 2 Mb windows, they find rates of crossover and gene conversion to be uncorrelated.
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Padhukasahasram B., Marjoram P., and Nordborg M. Estimating the rate of gene conversion on human chromosome 21. Am J Hum Genet 75 (2004) 386-397. Using simple multilocus summary statistics, the authors estimate rates of gene conversion and crossover in humans. The rates are based on patterns of LD, using the DNA from a worldwide sample of 20 chromosomes representing a 28 Mb region of chromosome 21. They estimate f to be ∼1.6, assuming a tract length of 500 bp. Estimating rates over overlapping 2 Mb windows, they find rates of crossover and gene conversion to be uncorrelated.
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(2004)
Am J Hum Genet
, vol.75
, pp. 386-397
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Padhukasahasram, B.1
Marjoram, P.2
Nordborg, M.3
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46
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0345730814
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Linkage disequilibrium patterns across a recombination gradient in African Drosophila melanogaster
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Andolfatto P., and Wall J.D. Linkage disequilibrium patterns across a recombination gradient in African Drosophila melanogaster. Genetics 165 (2003) 1289-1305
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(2003)
Genetics
, vol.165
, pp. 1289-1305
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Andolfatto, P.1
Wall, J.D.2
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47
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33646188774
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Relative influences of crossing over and gene conversion on the pattern of linkage disequilibrium in Arabidopsis thaliana
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The authors examine rates of gene conversion in Arabidopsis thaliana, using a genome-wide survey consisting of 1347 fragments (500-600 bp each) sequenced in 96 accessions. To do so, they perform coalescent simulations with growth parameters that match the observed allele frequency spectrum, and a crossover rate estimated using the method of Hudson [6]. They then find gene conversion parameters that match the observed LD patterns in their data. They find, on average, that f = 1, or that the crossover rate and gene conversion rate are both ∼0.3/kb, assuming a tract length of 100 bp.
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Plagnol V., Padhukasahasram B., Wall J.D., Marjoram P., and Nordborg M. Relative influences of crossing over and gene conversion on the pattern of linkage disequilibrium in Arabidopsis thaliana. Genetics 172 (2006) 2441-2448. The authors examine rates of gene conversion in Arabidopsis thaliana, using a genome-wide survey consisting of 1347 fragments (500-600 bp each) sequenced in 96 accessions. To do so, they perform coalescent simulations with growth parameters that match the observed allele frequency spectrum, and a crossover rate estimated using the method of Hudson [6]. They then find gene conversion parameters that match the observed LD patterns in their data. They find, on average, that f = 1, or that the crossover rate and gene conversion rate are both ∼0.3/kb, assuming a tract length of 100 bp. They also estimate rates of crossover and gene conversion across 14 genome-wide 2-Mb windows - each window having, on average, 18 fragments - and find that variable rates of f, crossover, and gene conversion across these windows fit the data significantly better than either fixing f across regions or taking an identical crossover and gene conversion rate in all regions. Furthermore, they find estimated rates of crossover and gene conversion across 43 such 2-Mb windows to be uncorrelated.
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(2006)
Genetics
, vol.172
, pp. 2441-2448
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Plagnol, V.1
Padhukasahasram, B.2
Wall, J.D.3
Marjoram, P.4
Nordborg, M.5
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48
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3843126537
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Estimating recombination rates using three-site likelihoods
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Wall J.D. Estimating recombination rates using three-site likelihoods. Genetics 167 (2004) 1461-1473
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(2004)
Genetics
, vol.167
, pp. 1461-1473
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Wall, J.D.1
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49
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Linkage disequilibrium and recombination
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Balding D.J., Bishop M., and Cannings C. (Eds), Wiley
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Hudson R.R. Linkage disequilibrium and recombination. In: Balding D.J., Bishop M., and Cannings C. (Eds). Handbook of Statistical Genetics (2001), Wiley 309-323
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(2001)
Handbook of Statistical Genetics
, pp. 309-323
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Hudson, R.R.1
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50
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A new statistical method for haplotype reconstruction from population data
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Stephens M., Smith N.J., and Donnelly P. A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68 (2001) 978-989
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(2001)
Am J Hum Genet
, vol.68
, pp. 978-989
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Stephens, M.1
Smith, N.J.2
Donnelly, P.3
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