GENEHUNTER-IMPRINTING

GENEHUNTER-IMPRINTING (GHI, version 1.3) is a modification of the GENEHUNTER software package (Kruglyak et al. 1996; Kruglyak and Lander 1998). It allows for a parametric multi-marker linkage analysis of dichotomous traits caused by imprinted genes – that is, of traits showing a parent-of-origin effect. By specification of two heterozygote penetrance parameters, paternal and maternal origin of the disease allele can be treated differently in terms of probability of expression of the trait. Therefore, a disease model which accounts for imprinting includes four penetrances instead of only three. For an analysis with a four-penetrance imprinting model, the command 'imprinting on' needs to be entered at the beginning of a GENEHUNTER-IMPRINTING session. Otherwise, LOD scores are calculated under a standard three-penetrance model, in the same way as with the original GENEHUNTER.

The imprinting extension does not affect NPL-score calculation or other types of analysis available with the original GENEHUNTER software (affected sib pair, QTL, and TDT analyses).

More information about GENEHUNTER-IMPRINTING can be found in the file INSTALL.ghi that is included in the archives provided below. Please also see the on-line help for details, e.g. by typing 'help load markers' or 'help imprinting' at the GHI prompt, or refer to the PostScript version of the online help (file ghi.ps). Please note that the program extension GENEHUNTER-MODSCORE offers all of the functionality of GENEHUNTER-IMPRINTING and also includes further methodological and algorithmic improvements. It is, however, still useful to employ GENEHUNTER-IMPRINTING (version 1.3) if X-chromosomal loci should be analyzed, since GENEHUNTER-MODSCORE can only handle (pseudo)autosomal loci.

• Strauch K, Fimmers R, Kurz T, Deichmann KA, Wienker TF, Baur MP (2000): Parametric and nonparametric multipoint linkage analysis with imprinting and two-locus-trait models: application to mite sensitization. American Journal of Human Genetics 66:1945-1957.

• Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES (1996): Parametric and nonparametric linkage analysis: a unified multipoint approach. American Journal of Human Genetics 58:1347-1363
• Kruglyak L, Lander ES (1998): Faster multipoint linkage analysis using Fourier transforms. Journal of Computational Biology 5:1-7
• Markianos K, Daly MJ, Kruglyak L (2001): Efficient multipoint linkage analysis through reduction of inheritance space. American Journal of Human Genetics 68:963-977