University of Virginia
 

 
 

GeneFinder

GeneFinder uses Generalized Estimating Equations (GEE, Liang and Zeger 1986) to estimate the location of susceptibility genes based on the multipoint IBD sharing among affected sib pairs. GeneFinder continues a standard linkage software such as MERLIN by providing a more reasonable gene location estimation and the corresponding confidence interval estimate. In addition, GeneFinder provides a variety of linkage extensions such as adjusting for covariate heterogeneity, joint analysis of two linked disease susceptibility loci, linkage conditional on a known locus, etc.

Recently I rewrote GeneFinder using some of the MERLIN codes, and implemented more linkage models. The new version is fully compatible with MERLIN and ready to handle large linkage datasets consisting of thousands of families and markers.

  1. Input files
  2. Extensions of GeneFinder
  3. Download
  4. References

1. INPUT FILES

GeneFinder requires a data file, a pedigree file, a map file, and an IBD file. The following command line specifies the four types of input files and performs a GEE analysis:

prompt> gf -d ex.dat -p ex.ped -m ex.map -i ex.ibd --gee
The format of input files is fully compatible with MERLIN format. Some other formats such as LINKAGE and GENEHUNTER are also supported. You may read MERLIN tutorial for details of MERLIN input files.


2. LINKAGE EXTENSIONS

GeneFinder has been extended in a number of ways. The following genetic models have been implemented:

  • Localization of disease susceptibility gene using multipoint markers (Liang et al. 2001)
    prompt> gf -d ex.dat -p ex.ped -i ex.ibd --gee
    
  • Gene localization incorporating the effect of a covariate (Glidden et al. 2003)
    prompt> gf -d ex.dat -p ex.ped -m ex.map -i ex.ibd --cgee --cov 1 
  • Gene localization conditional on a gene at another chromosome (Chiu and Liang 2004)
    prompt> gf -d ex.dat -p ex.ped -m ex.map -i ex.ibd -a addition.ibd --cgee --condition 31.4
  • Localization of two linked disease genes (Biernacka et al. 2004)
    prompt> gf -d ex.dat -p ex.ped -m ex.map -i ex.ibd --twolocus 80
    prompt> gf -d ex.dat -p ex.ped -m ex.map -i ex.ibd --twolocus 80 --cov
  • Gene localization incorporating parent-of-origin effect (Chen et al. unpublished)
    prompt> gf -d ex.dat -p ex.ped -m ex.map -i ex.s15 --poo
  • Gene localization using relative pairs other than sib pairs (Schaid et al. 2005)


3. DOWNLOAD GeneFinder 1.2.7

Executables (2/21/2008): Windows | Linux 32 bits | Linux 64 bits

Version 1.1.9 (6/9/2004) and earlier versions have a different interface. More details are described here.


4. REFERENCE

  1. Biernacka JM, Sun L, Bull SB (2005) Simultaneous localization of two linked disease susceptibility genes. Genet Epidemiol 28:33-47 [PDF]
  2. Chiu YF, Liang KY (2004) Conditional multipoint linkage analysis using affected sib pairs: an alternative approach. Genet Epidemiol 26:108-115 [PDF]
  3. Glidden DV, Liang KY, Chiu YF, Pulver AE (2003) Multipoint affected sibpair linkage methods for localizing susceptibility genes of complex diseases. Genet Epidemiol 24:107-117 [PDF]
  4. Liang KY, Chiu YF, Beaty TH (2001) A robust identity by descent procedure using affected sib pairs: a multipoint approach for complex diseases. Hum Hered 51: 64-78 [PDF]
  5. Liang KY, Chiu YF, Beaty TH, Wjst M (2001) A multipoint analysis using affected sib pairs: incorporation of linkage evidence from unlinked regions. Genetic Epidemiology 21: 105-122 [PDF
  6. Liang KY, Huang CY, Beaty TH (2000) A unified sampling approach for multipoint analysis of qualitative and quantitative traits in sib pairs. Am J Hum Genet 66: 1631-1641 [PDF]
  7. Liang KY, Zeger SL (1986) Longitudinal data analysis using generalized linear models. Biometrika 73: 13-22 [PDF]
  8. Schaid DJ, Sinnwell JP, Thibodeau SN (2005) Robust multipoint identical-by-descent mapping for affected relative pairs. Am J Hum Genet 76:128-138 [PDF]

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Last updated: February 21 2008 by Wei-Min Chen