Pseudomarker is likelihood-based analysis of "model-free" test of linkage and/or linkage disequilibrium. Algorithms uses disease phenotype to generate a marker-like genotype (=pseudomarker).Then linkage and LD analysis are performed for each marker locus vs. "pseudomarker" marker locus by using special version of ILINK from FASTLINK 4.1P software package.
Different inheritance models can be tried, both with and without LD: dominant & recessive models (and "model-based" analysis).
Nuisance parametersPseudomarker uses ILINK to estimate allele frequencies, haplotype frequencies (i.e., LD between marker loci) and recombination fractions as nuisance parameters for pseudomarker and "model-based" analysis.
This estimates the best value for each parameter separately under null and alternative hypotheses. (you get best maximum likelihood over nuisance parameters). You don’t have to worry about errors in these parameters leading to false positives.
Pedigree dataDifferent kind of data structures can be combined for more powerful joint analysis:
Pseudomarker can use of all the data jointly to extract the maximum linkage and association information possible.
Input files are LINKAGE formatted pedigree (pedin.dat) and locus (datain.dat) files. Pseudomarker analysis options are specified in command line and those are:
------------------------------------------------------------------------------- Program pseudomarker 0.9.7 BETA - 14th of May 2003 Copyright (C) 2000-2003 Tero Hiekkalinna and Joseph D. Terwilliger Program for Joint linkage and LD analysis, see readme.txt for details If you find a bug, send email to: tero.hiekkalinna@helsinki.fi ------------------------------------------------------------------------------- Usage: pseudomarker [argument(s)] Pseudomarker linkage/LD analysis: -d dominant pseudomarker analysis -r recessive pseudomarker analysis -m model-based analysis (parameters from data file) -a runs all analysis Parametric linkage analysis: -p parametric 2-point linkage analysis (MLINK) Other: -i some info about pseudomarker
Example if you want ro run dominant and recressive analysis:
pseudomarker -d -r
Pseudomarker output file is pseudo.out (example 1 here and pseudomarker graphical output example 2 here) and it contains 5 different statistical tests (look only for p-value statistics!):
Two tests for LD are comparable to ANALYZE package association tests. LD given Linkage can be compared to HHRR and Linkage given LD can be compared to TDT, but pseudomarker tests are more powerful (see article for details).
Tero Hiekkalinna and Joseph D. Terwilliger
Linkage Analysis in the Presence of Errors IV: Joint Pseudomarker Analysis of Linkage and/or Linkage Disequilibrium on a Mixture of Pedigrees and Singletons When the Mode of Inheritance Cannot Be Accurately Specified. Harald H. H. Göring and Joseph D. Terwilliger (Am. J. Hum. Genet. 66:1310-1327, 2000).
PubMed linkPseudomarker 0.9.6 (BETA) documentation
