Description
This track shows recombination rates measured in centiMorgans per
Megabase.
It is based on the HapMap Phase I data, release 16a, and Perlegen data (Hinds et al., 2005).
Observations from sperm studies (Jeffreys et al., 2001) and
patterns of genetic variation (McVean et al., 2004; Crawford
et al., 2004) show that recombination rates in the human
genome vary extensively over kilobase scales and that much
recombination occurs in recombination hotspots. This provides an
explanation for the apparent block-like structure of linkage
disequilibrium (Daly et al., 2001; Gabriel et al.,
2002).
Fine-scale recombination rate estimates provide a new route to
understanding the molecular mechanisms underlying human recombination.
A better understanding of the genomic landscape of human recombination
rate variation would facilitate the efficient design and analysis of
disease association studies and greatly improve inferences from
polymorphism data about selection and human demographic history.
Display Conventions and Configuration
This annotation track may be configured in a variety of ways to highlight
different aspects of the displayed data. The graphical configuration options
are shown at the top of the track description page.
For more information, click the
Graph
configuration help link.
Methods
Fine-scale recombination rates are estimated using the reversible-jump
Markov chain Monte Carlo (MCMC) method (McVean et al., 2004). This
approach explores the posterior distribution of fine-scale recombination
rate profiles, where the state-space considered is the distribution of
piece-wise constant recombination maps. The Markov chain explores the
distribution of both the number and location of change-points, in addition
to the rates for each segment. A prior is set on the number of
change-points that increases the smoothing effect of trans-dimensional
MCMC, which is necessary because of the composite-likelihood scheme
employed.
This method is implemented in the package
LDhat,
which includes full details of installation and implementation.
A block-penalty of five was used (calibrated by simulation
and comparison to data from sperm-typing studies). Each region was
analyzed as a single run with 10,000,000 iterations, sampling every 5000th
iteration and discarding the first third of all samples as burn-in. The
mean posterior rate for each SNP interval is the value reported. Because of
the non-independence of the composite likelihood scheme,
the quantiles of the sampling distribution do not reflect true uncertainty
and are therefore not given.
Estimates were generated separately from each of the four HapMap
populations, and then combined to give a single figure. Differences between
populations are not significant.
Validation
This approach has been validated in three ways: by extensive
simulation studies and by comparisons with independent estimates of
recombination rates, both over large scales from the genetic map and
over fine scales from sperm analysis. Full details of validation can be
found in McVean et al. (2004) and Winckler et al. (2005).
Credits
The HapMap data are based on HapMap
release 16a; the Perlegen data are from Hinds et al. (2005).
The recombination rates were ascertained by Simon Myers from the
Mathematical Genetics Group at the University of Oxford.
References
Crawford, D.C., Bhangale, T., Li, N., Hellenthal, G., Rieder, M.J.,
Nickerson, D.A. and Stephens, M.
Evidence for substantial fine-scale variation in recombination
rates across the human genome.
Nat Genet. 36(7), 700-6 (2004).
Daly, M.J., Rioux, J.D., Schaffner, S.F., Hudson, T.J. and Lander, E.S.
High-resolution haplotype structure in the human genome.
Nat Genet. 29(2), 229-32 (2001).
Gabriel, S.B., Schaffner, S.F., Nguyen, H., Moore, J.M., Roy, J., Blumenstiel,
B., Higgins, J., DeFelice, M., Lochner, A., Faggart, M. et al.
The structure of haplotype blocks in the human genome.
Science 296(5576), 2225-9 (2002).
Hinds, D.A., Stuve, L.L., Nilsen, G.B., Halperin, E., Eskin, E., Ballinger, D.G., Frazer, K.A., Cox, D.R.
Whole-Genome Patterns of Common DNA Variation in Three Human Populations.
Science 307(5712), 1072-1079 (2005).
Jeffreys, A.J,. Kauppi, L. and Neumann, R.
Intensely punctate meiotic recombination in the class II region
of the major histocompatibility complex.
Nat Genet. 29(2), 217-22 (2001).
McVean, G.A., Myers, S.R., Hunt, S., Deloukas, P., Bentley, D.R. and Donnelly,
P.
The fine-scale structure of recombination rate variation in the
human genome.
Science 304(5670), 581-4 (2004).
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.
et al.
Comparison of fine-scale recombination rates in humans and
chimpanzees.
Science 308(5718), 107-11 (2005).
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