Welcome to GENEHUNTER-IMPRINTING version 2.1_r3 beta * What is GENEHUNTER-IMPRINTING GENEHUNTER-IMPRINTING is a modification of the GENEHUNTER software package (version 2.1_r3 beta). It allows to perform parametric (LOD-score) analysis of 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, an imprinting disease model 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 GENEHUNTER. The imprinting extension does not affect NPL-score calculation or other types of analysis newly available with GENEHUNTER version 2 (affected sib pair, QTL, and TDT analyses). See the on-line help for details, e.g. by typing 'help load markers' or 'help imprinting' at the prompt. For some of the additional capabilities available since original version 2 named above, identity-by-descent probabilities need to be computed and stored for all pairs of relatives in a pedigree during the execution of 'scan pedigrees'. This can consume a lot of time and, hence, take away the computational advantages of version 2.1 beta over previous versions. Therefore, if only LODs (with or without imprinting) and NPLs are to be calculated, the above-named i.b.d. calculation should be left turned off ('compute sharing off'). This is the standard setting for the imprinting version, differing from the original v2.1 beta for which 'compute sharing on' is the standard. This is the only point where, for good reasons, GENEHUNTER-IMPRINTING v2.1 beta is not compatible to the original GENEHUNTER v2.1 beta. Note that this version only allows an analysis for autosomal loci. In case you want to perform an analysis for the X chromosome with imprinting, please use the xghi executable of GENEHUNTER-IMPRINTING version 1.3. Further modifications include the following: - Family and individual IDs do not need to be integers, but may contain other characters as well. - A new NPL scoring function, 'hom', has been implemented. It is similar to the 'all' scoring function, but uses both alleles of each affected individual at the same time, instead of choosing one out of two alleles. Type 'help score' at the prompt for details. - If NPL analysis is turned off ('analysis lod'), calculation is truly omitted, not just the score report. This accelerates calculation of LOD scores. - An array of memory (post_pscore/p_score in newcombo.c), which was allocated for every family but never used, has been removed. This allows to analyze samples that contain a larger number of pedigrees. * What is GENEHUNTER 2 GENEHUNTER 2 is an extension of the GENEHUNTER software that provides the researcher with a much wider range of analyses for performing linkage and disequilibrium analyses. The backbone of the system is the same as GENEHUNTER - the very rapid extraction of complete multipoint inheritance information from pedigrees of moderate size. This information is then used in exact computation of multipoint LOD scores, non-parametric linkage statistics, and now in a wide range of sibpair analyses (as in MAPMAKER/SIBS) and a new variance components analysis. In addition, several TDT analyses are also available for searching for association/disequlibrium in addition to linkage. As before, quick calculations involving dozens of markers, even in pedigrees with inbreeding and marriage loops, is possible with GENEHUNTER 2. Additionally, the multipoint inheritance information allows the reconstruction of maximum-likelihood haplotypes for all individuals in the pedigree and information content mapping which measures the fraction of the total inheritance information extracted from the marker data. All of these calculations are performed the same user-friendly environment as in GENEHUNTER. * How to Obtain GENEHUNTER-IMPRINTING The zipped GENEHUNTER-IMPRINTING v2.1_r3 tar file, ghi-2.1_r3.tar.gz, can be obtained by sending an e-mail to Konstantin Strauch: strauch@imsdd.meb.uni-bonn.de * How to Install GENEHUNTER-IMPRINTING To extract the GENEHUNTER-IMPRINTING files from this file, create a subdirectory for the program, move the ghi-2.1_r3.tar.gz file into it, and enter the commands: gunzip ghi-2.1_r3.tar.gz tar xvpf ghi-2.1_r3.tar The directory will now be filled with the following files: Makefile - Unix Makefile for compilation of GENEHUNTER-IMPRINTING Makefile.aix - special Makefile for IBM/AIX machines ghi.help - on-line help file - do not edit! ghi.ps - PostScript version of on-line help for printing linkloci.dat - sample marker data file linkloci.imp - sample marker data file with an imprinting trait model linkped.pre - sample pedigree data file INSTALL.ghi - this installation document COPYRIGHT.ghi - copyright and licensing agreement for GENEHUNTER-IMPRINTING and GENEHUNTER along with the subdirectories src and ansilib which contain the source code for the program. If the extraction is successful, you can now delete the ghi-2.1_r3.tar archive. * Compiling GENEHUNTER-IMPRINTING You need to compile the code to create an appropriate executable version for your particular system. One or two simple changes must be made to the Makefile: 1) line 6 (SYS= -D_SYS_OSF) must be replaced with one of the following: SYS= -D_SYS_SUNOS - for compilation on SUN machines SYS= -D_SYS_OSF - for compilation on DEC/Alpha machines, as well as on i386 machines running LINUX SYS= -D_SYS_ULTRIX - for compilation on Ultrix systems SYS= -D_SYS_HPUX - for compilation on HP workstations SYS= -D_SYS_AIX - for compilation on IBM/AIX RISC systems SYS= -D_SYS_SOLARIS - for compilation on Solaris machines If your system is not listed among those above, you can probably use one of the above definitions anyway - for example -D_SYS_OSF adheres to the ANSI standard and can be used with almost any ANSI compiler. For IBM/AIX RISC systems, a special Makefile is provided. It can be activated by entering the following commands: mv Makefile Makefile.sav mv Makefile.aix Makefile 2) line 25 in Makefile (CC = gcc) determines the C-compiler to be called and should be replaced if another C-compiler is used on your system (for example, CC = cc) After the Makefile is edited for your system, the Unix command "make" should automatically create the executable "ghi" appropriate for your system. If compilation is unsuccessful, contact your system administrator for assistance first as he or she will be familiar with bringing code to your particular system. If further assistance is required, feel free to contact us for help. * Getting Ready to Run It will often be useful to store your data in a separate subdirectory from the GENEHUNTER-IMPRINTING program (for various reasons such as diskspace or to make the program available to multiple users). In such cases, it can be helpful to include the directory containing the GENEHUNTER-IMPRINTING program in your Unix path. In addition, to use the on-line help facility, you will need to inform the program where to find the help and related documents. For instance, if the subdirectory you created for the programs is named /home/GHI, you will want to change your .cshrc file as follows: 1. change the line which reads something like: set path=(. /bin /usr/local /usr/bin /etc) to include /home/GHI set path=(. /bin /usr/local /usr/bin /etc /home/GHI) 2. add the following line to the end of the file setenv GHI_DIR /home/GHI Now GENEHUNTER-IMPRINTING can be called from anywhere on your system by simply typing the executable name ghi. (If you wish to hardwire the GHI_DIR into the code, replace the body of get_code_directory in ansilib/syscode.c with the line: nstrcpy(buf,"",PATH_LENGTH); return(TRUE); and recompile.) * Using GENEHUNTER-IMPRINTING To run the program just type the name of the executable and the shell will start up. To get a quick start in running the commands enter 'help' at the prompt. * How to cite or get more information on GENEHUNTER-IMPRINTING K. Strauch, R. Fimmers, T. Kurz, K.A. Deichmann, T.F. Wienker, and M.P. Baur. "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 (June 2000). * How to cite or get more information on GENEHUNTER 2 L. Kruglyak, M.J. Daly, M.P. Reeve-Daly, and E.S. Lander. "Parametric and Nonparametric Linkage Analysis: A Unified Multipoint Approach". American Journal of Human Genetics 58:1347-1363 (June 1996). L. Kruglyak and E.S. Lander. "Faster Multipoint Linkage Analysis Using Fourier Transforms". Journal of Computational Biology 5:1-7 (1998).