Gene mapping via the ancestral recombination graph

Theor Popul Biol. 2002 Sep;62(2):215-29. doi: 10.1006/tpbi.2002.1601.

Abstract

We present a multilocus gene mapping method based on linkage disequilibrium, which uses the ancestral recombination graph to model the history of sequences that may harbor an influential variant. We describe the construction of a recurrence equation used to make inferences about the location of a trait-influencing mutation. We demonstrate how a Monte Carlo algorithm combined with a local importance sampling scheme can be used for mapping. We explain how to simulate the timing of events in the coalescent in the presence of recombination and mutation, which accomodates variable population size. We provide an example to illustrate the use of the method, which can be easily extended to more general situations. Although the method is computationally intensive and variation in the likelihood profiles can occur, the method offers a great deal of promise.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Mapping / methods*
  • Computer Simulation
  • Likelihood Functions
  • Linkage Disequilibrium*
  • Models, Genetic*
  • Monte Carlo Method
  • Mutation
  • Polymorphism, Genetic
  • Recombination, Genetic