Welcome to GENEHUNTER-PLUS * What is GENEHUNTER-PLUS GENEHUNTER-PLUS is a modification of the GENEHUNTER software package which produces output files containing the null and conditional distributions of the test statistic (in nullprobs.dat and probs.dat, respectively). These files can then be used as input to the ASM program which incorporates the allele sharing modeling for lodscores and likelihood ratio tests as developed by Kong and Cox (1997). It should be noted that the probs.dat file can become quite large (5MB or more) in certain situations. Users may wish to compress these files regularly for storage, uncompressing only when fitting the allele-sharing models provided by the ASM program. GENEHUNTER is a software package that allows 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 and in a powerful new method of non-parametric linkage analysis. Quick calculations involving dozens of markers, even in pedigrees with inbreeding and marriage loops, is possible with GENEHUNTER. In addition, 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 in a user-friendly environment familiar to MAPMAKER, SIBS, or HOMOZ users. * How to Obtain GENEHUNTER-PLUS The first step is to obtain the file ghp-1.2.tar.gz from our network site galton.uchicago.edu in the pub/kong subdirectory. This can be done via ftp or any number of network tools. Login with the username anonymous and then enter your e-mail address as a password. * How to Install GENEHUNTER-PLUS To extract the GENEHUNTER-PLUS files from this file, create a subdirectory for the program, move the ghp-1.2.tar.gz file into it, and enter the commands: gunzip ghp-1.2.tar.gz tar xvpf ghp-1.2.tar The directory will now be filled with the following files: ghp.solaris - the GENEHUNTER-PLUS executable for Sun Sparcstations (Solaris OS) gh.help - on-line help file - do not edit! gh.ps - PostScript version of on-line help for printing Makefile - Unix Makefile for compilation on other systems linkloci.dat - sample marker data file linkped.pre - sample pedigree data file xghp.solaris - the GENEHUNTER-PLUS X chromosome executable for Sun Sparcstations (Solaris OS) xgen.loc - sample X chromosome marker data file xgen.ped - sample X chromosome pedigree data file INSTALL.ghp - this installation document COPYRIGHT.ghp - copyright for GENEHUNTER-PLUS 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 ghp-1.2.tar archive. * Compiling GENEHUNTER-PLUS If you are planning to run GENEHUNTER-PLUS on a Sun Sparcstation running SOLARIS, you can use the precompiled executable "ghp.solaris". If you have another type of Unix machine, you must compile the code yourself to create an appropriate executable version. One or two simple changes must be made to the Makefile: 1) line 5 (SYS= -D_SYS_SOLARIS) 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 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) 2) line 12 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 "ghp" 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-PLUS 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-PLUS 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/GHP, 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/GHP set path=(. /bin /usr/local /usr/bin /etc /home/GH)P 2. add the following line to the end of the file setenv GHP_DIR /home/GHP Now GENEHUNTER-PLUS can be called from anywhere on your system by simply typing the executable name (ghp or ghp.solaris). (If you wish to hardwire the GHP_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-PLUS 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 basic' at the prompt. * How to cite or get more information on GENEHUNTER-PLUS A. Kong and N.J. Cox. "Allele-Sharing Models: LOD Scores and Accurate Linkage Tests". American Journal of Human Genetics 61:1179-1188 (November, 1997). * How to cite or get more information on GENEHUNTER 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).