## Description

This track shows recombination rates measured in centiMorgans/Megabase in ten ENCODE regions that have been resequenced:

- ENr112 (chr2)
- ENr131 (chr2)
- ENr113 (chr4)
- ENm010 (chr7)
- ENm013 (chr7)
- ENm014 (chr7)
- ENr321 (chr8)
- ENr232 (chr9)
- ENr123 (chr12)
- ENr213 (chr18)

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 disequlibrium (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 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.

For the ENCODE regions, a block-penalty of 5 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 ENCODE resequencing 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 data is based on HapMap release 16. The recombination rates were ascertained by Gil McVean 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).

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).