TY - JOUR

T1 - Application of Coalescent Methods to Reveal Fine-Scale Rate Variation and Recombination Hotspots.

AU - Fearnhead, Paul

AU - Harding, Rosalind M.

AU - Schneider, Julie A.

AU - Myers, Simon

AU - Donnelly, Peter

PY - 2004/8

Y1 - 2004/8

N2 - There has been considerable recent interest in understanding the way in which recombination rates vary over small physical distances, and the extent of recombination hotspots, in various genomes. Here we adapt, apply, and assess the power of recently developed coalescent-based approaches to estimating recombination rates from sequence polymorphism data. We apply full-likelihood estimation to study rate variation in and around a well-characterized recombination hotspot in humans, in the ß-globin gene cluster, and show that it provides similar estimates, consistent with those from sperm studies, from two populations deliberately chosen to have different demographic and selectional histories. We also demonstrate how approximate-likelihood methods can be used to detect local recombination hotspots from genomic-scale SNP data. In a simulation study based on 80 100-kb regions, these methods detect 43 out of 60 hotspots (ranging from 1 to 2 kb in size), with only two false positives out of 2000 subregions that were tested for the presence of a hotspot. Our study suggests that new computational tools for sophisticated analysis of population diversity data are valuable for hotspot detection and fine-scale mapping of local recombination rates.

AB - There has been considerable recent interest in understanding the way in which recombination rates vary over small physical distances, and the extent of recombination hotspots, in various genomes. Here we adapt, apply, and assess the power of recently developed coalescent-based approaches to estimating recombination rates from sequence polymorphism data. We apply full-likelihood estimation to study rate variation in and around a well-characterized recombination hotspot in humans, in the ß-globin gene cluster, and show that it provides similar estimates, consistent with those from sperm studies, from two populations deliberately chosen to have different demographic and selectional histories. We also demonstrate how approximate-likelihood methods can be used to detect local recombination hotspots from genomic-scale SNP data. In a simulation study based on 80 100-kb regions, these methods detect 43 out of 60 hotspots (ranging from 1 to 2 kb in size), with only two false positives out of 2000 subregions that were tested for the presence of a hotspot. Our study suggests that new computational tools for sophisticated analysis of population diversity data are valuable for hotspot detection and fine-scale mapping of local recombination rates.

U2 - 10.1534/genetics.103.021584

DO - 10.1534/genetics.103.021584

M3 - Journal article

VL - 167

SP - 2067

EP - 2081

JO - Genetics

JF - Genetics

SN - 0016-6731

IS - 4

ER -