SimPed: A Simulation Program to Generate Haplotype and Genotype Data for Pedigree Structures

Abstract

With the widespread availability of SNP genotype data, there is great interest in analyzing pedigree haplotype data. Intermarker linkage disequilibrium for microsatellite markers is usually low due to their physical distance; however, for dense maps of SNP markers, there can be strong linkage disequilibrium between marker loci. Linkage analysis (parametric and nonparametric) and family-based association studies are currently being carried out using dense maps of SNP marker loci. Monte Carlo methods are often used for both linkage and association studies; however, to date there are no programs available which can generate haplotype and/or genotype data consisting of a large number of loci for pedigree structures. SimPed is a program that quickly generates haplotype and/or genotype data for pedigrees of virtually any size and complexity. Marker data either in linkage disequilibrium or equilibrium can be generated for greater than 20,000 diallelic or multiallelic marker loci. Haplotypes and/or genotypes are generated for pedigree structures using specified genetic map distances and haplotype and/or allele frequencies. The simulated data generated by SimPed is useful for a variety of purposes, including evaluating methods that estimate haplotype frequencies for pedigree data, evaluating type I error due to intermarker linkage disequilibrium and estimating empirical p values for linkage and family-based association studies.

Deciphering the fine-structure of tribal admixture in the Bedouin population using genomic data

“…We compared our method with several other approaches on real data from our laboratory and on simulated data generated with SimPed (Leal et al, 2005) (see Supplementary Appendix A and Supplementary Tables S2 and S3). The other approaches include exact inference using MERLIN, (Abecasis et al, 2001) approximated inference using PREST (Sun et al, 2002) and PLINK Method of Moments (MoM) kinship estimation (genome option).…”

Coordinated Conditional Simulation with SLINK and SUP of Many Markers Linked or Associated to a Trait in Large Pedigrees

“…The limitations on early versions of SUP have been removed and usage is simpler. Other simulation packages include SIMLINK [12] , SIMULATE [8] , SimPed [19] , SIMLA [21] , and ALLEGRO [22] . These five packages are all compared to the initial version of SUP in [5] , and to our knowledge have not changed much since 2006.…”

“…The techniques of gene dropping and sampling the recombination process can be used to generate a long series of markers along a hypothetical chromosome, and this was implemented, for example, in the software packages SIMULATE [8] , SimPed [19] and SimM [20] . However, to extend the capability to include a linked trait locus requires a third technique called a 'descent marker'.…”

Robustness of linkage maps in natural populations: a simulation study

“…Scenario 3 was identical to scenario 1, except that a 5% genotyping error was introduced at each locus. Genotypes were assigned to individuals in the mapping population using the SIMPED software (Leal et al 2005). SIMPED uses Monte Carlo simulation to assign genotypes to founder individuals based on user-defined allele frequencies.…”