Generation of sequence-based data for pedigree-segregating Mendelian or Complex traits.

Area of Science:

• Genetics
• Bioinformatics
• Computational Biology

Background:

• Analyzing next-generation sequence data for pedigrees is of significant interest.
• Limited rare variant analysis methods exist for pedigree data.
• Lack of software for simulating realistic pedigree sequence data hinders error evaluation.

Purpose of the Study:

• To develop a program for simulating genotype and phenotype data for pedigrees.
• To enable evaluation of type I and II errors for family-based rare variant methods.

Main Methods:

• Developed RarePedSim (Rare-variant Pedigree-based Simulator).
• Simulates region/gene-level genotype and phenotype data for any pedigree structure.
• Generates sequence variant data conditionally or unconditionally on phenotypes, or traits conditional on variant data.
• Supports realistic population demographic models or sequence-based studies.
• Annotates variant sites with position, allele frequencies, and functionality.

Main Results:

• RarePedSim is the only program efficiently generating both genotypes and phenotypes for rare variants, irrespective of pedigree structure.
• Generated data are in standard Linkage (.ped) and Variant Call (.vcf) formats.
• Enables evaluation of type I error and power for association methods.

Conclusions:

• RarePedSim facilitates the analysis of rare variants in pedigree data.
• The software supports various genetic models and trait types (complex and Mendelian).
• Data generated are ready for use in association studies, including mixed models and linkage analysis.