LDMhap

LDMhap implements multilocus linkage-disequilibrium mapping, extending the McPeek and Strahs multilocus model to incorporate a stepwise-mutation model for microsatellite markers and a general conditional-coalescent model with variable population size for fine-mapping disease genes.

Key Features:

• Multilocus model extension: Extends the McPeek and Strahs multilocus model to multilocus linkage-disequilibrium mapping.
• Stepwise-mutation model for microsatellite markers: Models microsatellite allele evolution using a stepwise-mutation model to represent realistic mutation processes.
• General conditional-coalescent model with variable population size: Models dependence among observed haplotypes via a general conditional-coalescent model that accounts for variable population sizes.
• Simulation studies: Performs simulations to evaluate impacts on disease gene location, mutation rate, and time to the most recent common ancestor of sampled haplotypes.

Scientific Applications:

• Disease gene mapping: Fine-maps disease genes by analyzing the decay of haplotype sharing.
• Population genetics studies: Investigates evolutionary dynamics and historical demography by modeling population structure and variable population sizes.
• Analysis of progressive myoclonus epilepsy data: Applied to analyze data from progressive myoclonus epilepsy in complex disease gene mapping contexts.

Methodology:

Implements a stepwise-mutation model for microsatellite markers; implements a general conditional-coalescent model with variable population size to capture haplotype dependence; and conducts simulation studies to assess effects on disease gene localization, mutation rate estimates, and time to the most recent common ancestor of sampled haplotypes.