Fine mapping--19th century style.
BACKGROUND
There is great interest in the use of computationally intensive methods for fine mapping of marker data. In this paper we develop methods based upon ideas originally proposed 100 years ago in the context of spatial clustering.


METHODS
We use spatial clustering of haplotypes as a low-dimensional surrogate for the unobserved genealogy underlying a set of genotype data. In doing so we hope to avoid the computational complexity inherent in explicitly modelling details of the ancestry of the sample, while at the same time capturing the key correlations induced by that ancestry at a much lower computational cost.


RESULTS
We benchmark our methods using the simulated Genetic Analysis Workshop 14 data, using 100 replicates of 4 phenotypes to indicate the power of our method. When a functional mutation relating to a trait is actually present, we find evidence for that mutation in 97 out of 100 replicates, on average.


CONCLUSIONS
Our results show that our method has the ability to accurately infer the location of functional mutations from unphased genotype data.
Molitor
John
J
Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90089-9011, USA. jmolitor@usc.edu
Zhao
Keyan
K
Marjoram
Paul
P
D003226:Congresses as Topic; D049673:History, 20th Century; D006801:Humans; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020161:Physical Chromosome Mapping / Q000266:history*; D015203:Reproducibility of Results