SimRVPedigree

SimRVPedigree simulates pedigrees ascertained by multiple disease-affected relatives to model familial patterns and rare variant segregation for studies using next-generation sequencing.

Key Features:

• Simulation of Ascertained Pedigrees: Simulates pedigrees ascertained due to multiple disease-affected relatives to support rare-disease and family-based variant discovery from next-generation sequencing data.
• Incorporation of Ascertainment Process: Integrates the ascertainment process into simulations to assess its influence on within-family relationship patterns and age of disease onset.
• Analysis of Familial Patterns: Models clustering of affected family members who segregate a rare disease variant and contrasts these patterns with sporadic disease occurrences.
• Insight into Age of Onset Anticipation: Demonstrates how ascertainment can produce apparent anticipation in age of onset among affected relatives.
• Limit on Proportion of Causal Variant Segregation: Estimates limits on the proportion of ascertained families that segregate a causal variant to inform study design and interpretation.

Scientific Applications:

• Genetic Research: Plan and interpret family-based studies aimed at identifying rare genetic variants using next-generation sequencing.
• Study Design Insight: Evaluate the implications of ascertainment and sampling design choices in familial genetic studies.

Methodology:

Implements a pedigree simulation approach that explicitly incorporates the ascertainment process to model familial relationships and age-of-onset patterns.