#MAPMAKER help file - do not edit! @TOPIC loading data commands: @load markers This command reads in the marker-locus data (allele frequencies for each genetic marker, frequency and penetrance information for the disease). The file may be in one of two formats: 1. Linkage parameter file (output from PREPLINK) See the file linkloci.dat as an example 2. Our internal marker information format (which contains the same information and also includes map distance between markers). See the file locdesc.dat as an example. This should be the first command of any HOMOZ session as this information is required by every subsequent step in the mapping process. @prepare pedigrees This command reads through a pedigree file and does some of the initial mapping set-up. The pedigree file may take one of two formats: 1. The LINKAGE pedigree input format (before running MAKEPED or doing any preprocessing!). Each line of this file must have the following structure: 3 12 8 9 1 2 1 1 2 8 3 0 0 4 6 1 3 ... (a) (b) (c) (d) (e) (f) (g) (h ------------------------) (a) pedigree name (b) individual ID # (c) father's ID # (d) mother's ID # (e) sex (1=MALE, 2=FEMALE) (f) affectation status (1=UNAFFECTED, 2=AFFECTED) (g) liability class (optional) - classes specified in marker data file (h) marker genotypes A 0 in any of these positions (as in the the genotypes for the third marker above) indicates missing data. See the file linkped.pre as an example. Any untyped children are discarded from consideration at this stage. If the family is too large to be computationally tractable, the 'prepare pedigrees' will inform you of this and ask you to specify children that may be discarded from mapping to reduce the complexity. Usually children that are unaffected and/or only partially informative are your best bets to discard. Please consult documentation for the Linkage program if you need any further information regarding the Linkage file formats. 2. Our internal pedigree file format. The data is stored as follows: 1st line: 2nd line: (lines after this, one for each marker, indicating genotypes - be sure to include the disease as a marker in this format as follows: 2 2 = affected, 1 2 = carrier) D1MIT19 1 3 2 4 1 4 1 2 ... ... The inbreeding value number should be one of the following integers representing the inbred relationship of the parents in the pedigree: 5 = uncle-niece or aunt-nephew 6 = first cousins 7 = first cousins once removed 8 = second cousins 9 = second cousins once removed 10 = third cousins 0 = NO INBREEDING The ancestors value should be either 1 (if the mother and father share one common ancestor) or 2 (if they share two common ancestors) See the file inbred.ped as an example. In either of these file formats, you may enter as many pedigrees as you wish in a single file. After completing the "load markers" and "prepare pedigrees" steps, you are ready to map. If you'd like to become familiar with the program using the sample data then you can run the following sequence: load markers linkloci.dat prepare pedigrees linkped.pre or try load markers locdesc.dat prepare pedigrees inbred.ped *** IMPORTANT *** Keep in mind when creating files that there must be a one-to-one correspondence (IN ORDER AND NUMBER) between the markers described in the marker data file and the markers that have genoptypes listed for them in the pedigree file. In addition, these files should contain data for one set of parents and children (with their direct ancestors if available). Additional branches of families other than the parents and children of interest should not be included. Genotypes and phenotypes of individuals other than the parents and children will be ignored. @TOPIC mapping commands @scan The main mapping command in HOMOZ is the scan command. It reads the prepared pedigree information and the genetic map specified by the 'use' command and calculates a LODscore for the likelihood of the presence of the disease locus at many positions throughout the map. If more than one pedigree have been specified in the pedigree file, the scan command will analyze these families one at a time, reporting the LODscores found at each position in each family, as well as producing a total LODscore plot at the end. A text copy of this output will be stored as well as a PostScript plot of the LODscores. The following set of commands affect the functionality of the scan command so that the user can obtain the maps most interesting to him or her. This plain text version is suitable for loading into other graphing packages as well. @use The 'use' command is used to select the current map that the 'scan' command will operate on. It is called in the following manner: use ... If marker names are specified (as they can be using our internal marker file format), markers may be specified using those names. If not, then they must be specified numerically (1 being the first listed in the marker locus file - the affectation locus does not count in this numbering scheme). Distances may be specified as either recombination-fractions or centiMorgans, with the necessary caveat that any distance below 0.5 is assumed to be a recombination-fraction and any greater than or equal to 0.5 is assumed to be in centiMorgans. When data is entered using our internal marker file format, HOMOZ will create a default map using each marker and the distances specified in the file. When data is entered using the Linkage format, there is no map created automatically and the 'use' command MUST BE RUN BEFORE A SCAN CAN BE RUN. For ease, the use command can be stored in a file and loaded using the 'run' command. This enables you to use a map in many session without having to re-enter it each time. (see the help on the 'run' command for details) @off end This command controls how far before the first marker and after the last marker in a map LODscores will be calculated. For example, if this value is set to 10.0, then subsequent scan commands will begin calculating LODscores 10 cM before the first marker and continue stepping through until 10 cM after the last marker. The default value of 'off end' is 20.0 cM. Calling 'off end' with no arguments causes HOMOZ to report the current value. Distances may be specified as either recombination-fractions or centiMorgans, with the necessary caveat that any distance below 0.5 is assumed to be a recombination-fraction and any greater than or equal to 0.5 is assumed to be in centiMorgans. @increment This command controls the frequency with which the 'scan' command calculates a new LODscore in scanning the map. If 'increment distance 2.0' is entered, the 'scan' command will calculate a map every 2.0 cM throughout the genetic map selected (regardless of the position of markers in that map) as follows (in this example the off end distance is set to 6.0 cM): -6.0 (6 cM before the first marker), -4.0, -2.0, 0.0 (the position of the first marker), 2.0, 4.0, ...etc...until 6.0 cM after the last locus. If 'increment step 5' is selected, the scan command will calculate LOD scores at 5 equally spaced positions in each map interval. For example, if your map has three markers separated by distance of 10 and 15 cM and the off end distance is set to 5 cM, maps will be calculated at the following positions: -5.0, -4.0, -3.0, -2.0, -1.0 (equally spaced in the 5cM before the first marker) 0.0, 2.0, 4.0, 6.0, 8.0 (equally spaced in the 10 cM interval) 10.0, 13.0, 16.0, 19.0, 22.0 (equally spaced in the 15 cM interval) 25.0, 26.0, 27.0, 28.0, 29.0, 30.0 (equally spaced in the 5cM after the map) The default value of 'increment' is 1.0 cM. Calling 'increment' with no arguments causes HOMOZ to report the current value. Note that the first ('distance') method is not guaranteed to hit every marker position and should be considered inferior to the second ('step') method, which will compute a map at every marker position. @map function This command controls which mapping function is used to convert centiMorgans to recombination-fractions and back again both in the input and output of the program and in the internal calculations. Currently only Haldane and Kosambi map functions are available. The default 'map function' is Kosambi. @allele frequencies The 'allele frequencies' command controls how the allele frequencies supplied in the marker data file are utilized by the 'scan' command. Argument :: Result given The 'scan' command uses the allele-frequencies given in the marker data file to compute probabilities. thresholded The 'scan' command uses the given allele-frequencies unless the are below the given value. Any frequency below this given value is considered to have this given value. The default case is that the 'allele frequencies' given are used. Typing 'allele frequency' with no argument causes HOMOZ to report the current value. @pedigrees The 'pedigrees' command allows the user to select which pedigrees will be analyzed in subsequent calls to 'scan'. If you wish to analyze only a subset of the pedigrees in your data file (for example, ped2 and ped6), you would enter the command: homoz:3> pedigrees ped2 ped6 The following pedigrees are in use: ped2 ped6 If you wish to analyze all pedigrees in the data file (the default condition when a new data file is prepared), you could enter: homoz:4> pedigrees all The following pedigrees are in use: ped1 ped2 ped3 ped4 ped5 ped6 ped7 Keep in mind that in the above example, the names 'ped1', 'ped2', etc., represent the names that are listed in the original pedigree file. Entering "pedigrees" with no argument causes HOMOZ to report the current list of pedigrees under analysis. If you wish to remove pedigrees from the list of active pedigrees under analysis, see the 'remove pedigrees' command. @remove pedigrees The 'remove pedigrees' command enables the user to remove specific pedigrees from analysis by the 'scan' command. If, for example, you wished to exclude ped5 from your analysis, the command: homoz:5> remove pedigrees ped5 The following pedigrees are in use: ped1 ped2 ped3 ped4 ped6 ped7 would effect the appropriate change. @units The 'units' command enables the user to select whether the output from the 'scan' command appears in recombination-fractions (rf) or centiMorgan distance (cM). The conversion function for centiMorgans to recombination fractions can be set using the 'map function' command. When HOMOZ is started up, Kosambi centiMorgans are selected as output units. @end