TLINKAGE

TLINKAGE performs two-trait-locus, two-marker-locus linkage analysis as an extension of LINKAGE programs to map complex disease loci and evaluate linkage information in multifactorial inheritance scenarios.

Key Features:

• Two-Trait-Locus, Two-Marker-Locus Analysis: Implements simultaneous mapping of two trait loci to two genetic marker loci for multilocus linkage analysis.
• Comparison and Utility Assessment: Compares two-trait-locus, two-marker-locus linkage analysis with standard single-locus methods both with and without allowance for heterogeneity.
• Handling Bilineal Pedigrees: Assesses the information content provided by bilineal pedigrees relative to unilineal pedigrees in linkage studies.
• Model Evaluation: Computes and compares expected maximum lod scores under dominant-or-recessive, threshold, and dominant-or-dominant models, including comparisons to one-locus models with heterogeneity.
• Significance Assessment Strategies: Includes strategies for evaluating the statistical significance of linkages assumed in complex multilocus models.

Scientific Applications:

• Multifactorial disease mapping: Mapping genetic loci contributing to common familial diseases such as diabetes, psoriasis, certain cancers, and schizophrenia by accommodating multilocus inheritance and complex pedigree structures.

Methodology:

Extends LINKAGE programs to perform two-trait-locus, two-marker-locus analysis; compares these multilocus analyses to single-locus methods with and without heterogeneity; assesses bilineal versus unilineal pedigree information content; computes expected maximum lod scores for specified inheritance models; and applies strategies for significance assessment.