Fine-scale Genetic Mapping Based on Linkage Disequilibrium: Theory and Applications
M. Xiong, S.W. Guo
American Journal of Human Genetics,
60(6), 1513-1531 (June 1997)
Abstract
Linkage-disequilibrium mapping (LDM) recently has been hailed as
a powerful statistical method for fine-scale mapping of disease genes.
After reviewing its historical background and methodological
development, we present a general, mathematical, and conceptually
coherent framework for LDM that incorporates multilocus and
multiallelic markers and mutational processes at the marker and
disease loci. With this framework, we address several issues relevant
to fine-scale mapping and propose some efficient computational
methods for LDM. We implement various LDM methods that
incorporate population growth, recurrent mutation, and marker
mutations, on the basis of a general framework. We demonstrate
these methods by applying them to published data on cystic fibrosis,
Huntington disease, Friedreich ataxia, and progressive myoclonus
epilepsy. Since the genes responsible for these diseases all have been
cloned, we can evaluate the performance of our methods and can
compare ours with that of other methods. Using the proposed
methods, we successfully and accurately predicted the locations of
genes responsible for these diseases, on the basis of published data
only.
Association Studies