TWOLOC

TWOLOC performs two-locus linkage analysis of affected sib-pair data to detect and evaluate closely mapped susceptibility genes underlying human multifactorial diseases.

Key Features:

• Identity-by-Descent (IBD) Analysis: Employs IBD-based sib-pair linkage tests to evaluate individual markers or linked marker maps for potential linkage to a susceptibility gene.
• Multilocus Linkage Testing: Incorporates a maximum likelihood-based multilocus linkage test that accounts for interdependency between two closely mapped genes and interprets IBD distortion.
• Interaction Evaluation: Evaluates support for interactions between constituent susceptibility genes to assess their collective contribution to disease phenotypes.
• Simulation Studies: Uses simulation studies to investigate the size and power of tests for detecting a second linked susceptibility gene.

Scientific Applications:

• Genetic Linkage Analysis: Applied to affected sibling-pair data to identify polygenes and susceptibility loci contributing to complex human diseases.
• Gene-Gene Interaction Studies: Used to evaluate interactions between closely linked susceptibility genes in multifactorial disease architectures.

Methodology:

Maximum likelihood-based multilocus linkage tests, IBD-based sib-pair linkage testing, assessment of IBD distortion, testing hypotheses about gene-gene interactions, and simulation studies to evaluate test size and power.