GENEHUNTER

GENEHUNTER performs multipoint linkage analysis on pedigrees by extracting multipoint inheritance distributions and applying parametric and nonparametric (NPL) methods for LOD score computation, information-content mapping, and maximum-likelihood many-marker haplotype reconstruction.

Key Features:

• Multipoint Inheritance Information Extraction: Extracts complete multipoint inheritance information from general pedigrees using the multipoint inheritance distribution.
• Rapid Exact Multipoint LOD Score Computation: Computes exact multipoint LOD scores rapidly for dozens of highly polymorphic markers while accommodating pedigree loops and missing data.
• Non-Parametric Linkage (NPL) Analysis: Implements an NPL method robust to inheritance-mode uncertainty and offering power competitive with parametric analyses.
• Information-Content Mapping: Quantifies the fraction of total inheritance information captured by available marker data and identifies genomic regions where additional marker typing would be most beneficial.
• Maximum-Likelihood Haplotype Reconstruction: Performs maximum-likelihood reconstruction of many-marker haplotypes in the presence of missing data.

Scientific Applications:

• Complex disease linkage studies: Performs multipoint linkage analysis to map genetic loci in complex disease studies using pedigrees of moderate size.
• Analyses with uncertain inheritance models: Enables linkage testing when the mode of inheritance is unknown by using robust nonparametric methods.
• Marker optimization and haplotype analysis: Guides marker typing decisions via information-content mapping and supports reconstruction of many-marker haplotypes from pedigree data with missing genotypes.

Methodology:

Captures multipoint inheritance information via a multipoint inheritance distribution, computes exact multipoint LOD scores, performs non-parametric linkage (NPL) analysis, generates information-content maps, and reconstructs many-marker haplotypes by maximum-likelihood.