CASPAR

CASPAR performs linkage analysis of polygenic diseases by analyzing genotype data from nuclear families with two unaffected parents and an affected sibling pair to test for genetic linkage using multiple polymorphic DNA markers, with explicit application to type I diabetes mellitus (insulin-dependent diabetes mellitus, IDDM).

Key Features:

• Linkage analysis: Uses affected sibling pair data from nuclear families with two unaffected parents and an affected sibling pair to detect linkage signals.
• Multiple polymorphic marker analysis: Analyzes multiple polymorphic DNA markers simultaneously to test linkage across multiple loci.
• Conditional linkage analysis: Performs conditional analyses by subdividing the population based on criteria at specific loci and then testing linkage at other loci.
• Conditioning on known susceptibility loci: Enables conditioning on established loci such as IDDM1 and IDDM2 when investigating additional loci like IDDM5 and IDDM7.
• Simulation-based significance assessment: Generates simulated datasets to determine the significance of LOD scores from affected sibling pair (ASP) tests and to address multiple testing.

Scientific Applications:

• Type I diabetes mellitus (insulin-dependent diabetes mellitus, IDDM): Investigates genetic susceptibility and interaction of loci in IDDM, including conditional testing of IDDM1, IDDM2, IDDM5, and IDDM7.
• Polygenic disease linkage studies: Applies to linkage analysis of other polygenic diseases using nuclear-family affected sibling pair designs to identify complex trait loci.

Methodology:

Generates simulated datasets to evaluate significance of LOD scores from affected sibling pair (ASP) tests and to address multiple testing in linkage analyses.