Version 3.0 is the fifth major release of Mega2. This version contains some important changes in Mega2's behaviour. Please consult the documentation for a detailed explanation of these changes.

Version 2.5 is the fourth major release of Mega2. This version contains many bug-fixes and new features. The user should consult this documentation for new features and bug-fixes prior to using version 2.5.

Version 2.3 had three revisions R2, R3, and R4 containing several bug-fixes. These bugs and the options they might affect are listed below.

Version 2.3 is the third major release of Mega2. This version and its revisions will be no longer supported, and their licenses expire on June 15, 2003.

The bug fixes listed on this page for version 2.2 and its revisions are also separately listed in the section Updated bug list .

• Bug-Fix: SAGE4 parameter file was wrong. The field-widths were not set correctly.


• Enhancement: Mega2 now allows to the user to specify an alternate location for the output files, the default is the current directory.


• Enhancement: An html-format page is created with links to input files, run summary files and output files, for easy access.


• Important Change: A new perl script is now included with the others, mega2log2html.pl for the creation of the html page.


• Enhancement: New Hardy-Weinberg options, two from the R "genetics" library, and Mendel version 5.0.


• Enhancement: We preserve run summaries for each run, by creating a unique directory identified by the run date and time, and storing the summaries within this directory.


• Bug-Fix: X-linked analysis was not working, caused Mega2 to crash.


• Bug-Fix: Alleles are not recoded if they are already numbered from 1 through N (N= number of alleles), and all N alleles are present in the data.


• Enhancement: New selection choice for counting genotypes for recoding alleles with the names file option.


• Enhancement: SOLAR option now also generates a TCL script that provides a function within the SOLAR environment to load in the pedigree, locus, map and phenotype files.


• Important Change: The trait-selection menu has changed. It DOES NOT include the markers by default in the "Combine" mode. See the trait menu section for more details.


• Important Change: Batch file keywords have changed: Markers_Selected is now Loci_Selected. Markers_Selected_Num is no longer valid. MEGA2 will produce a warning message and ignore this keyword.


• Enhancement: Untyped persons are not included in the per-person typing rate table in genotyping-rate summary. Instead the persons are listed at the end of the summary file.


• Bug-Fix: Since bash is not available on DEC-Alpha, the install script now uses "sh".


• Bug-Fix: In the BATCH mode, Mega2 appended new declarations for Value_MissingQuant to any existing MEGA2.BATCH file. This has been fixed.


• Bug-Fix: SAGE 4.0 parameter file now includes a default 0 as missing genotype value to prevent error messages in the GENIBD output about unrecognized genotype value.


• Bug-Fix: Mendel5 option created incorrect keys file.


• Bug-Fix: Duplicate names in the names files caused Mega2 to run incorrectly. These are detected and causes Mega2 to exit.

• Bug-Fix: SOLAR bug fixed: In the "loop-over traits" mode person ids in the phenotype file did not match person ids in the pedigree file.

• Important Change: Names file locus codes have been changed to match Merlin's lcous file format codes. Consult the section on Names file for details.


• Bug-Fix: SOLAR bug fixed: Mega2 crashed while looping over quantitative trait loci, one at a time.


• Bug-Fix: RECODE bug fixed: Mega2 crashed while recoding loci from names file, if there were no mapped loci.


• Bug-Fix: MERLIN bug fixed: Merlin analysis option menu was displayed twice.


• Bug-Fix: GENOTYPING ERROR simulation mode bug fixed: Locus selection was not working properly.


• Bug-Fix: SIMWALK2 bug fixed: Location scores option produced an incorrect penetrance file for multiple affection liability classes.


• Enhancement: Improved messages with respect to pedigree format (pre- or post-makeped) detection. Warns the user if there are 0s in the fifth column, and proceeds to read in post-makeped.

• Bug-Fix: ASPEX bug fixed - nuclear pedigree naming/numbering options did not allow numbering with extensions.


• Bug-Fix: SPLINK bug fixed - did not put all markers into one file, when user selected the global output file option from the file-selection menu.


• Bug-Fix: S.A.G.E. 4.x bug fixed - The format statement in the parameter file did not match pedigree records.


• Bug-Fix: R-graphics bug fixed - The output file was not renumbered according to the chromosome correctly.


• Enhancement: Combined shell-scripts - For SimWalk2, Merlin and Allegro options, a combined shell script is generated if there are multiple traits to loop over. This runs the trait-specific shell-scripts, then the R-graphics script if appropriate. See details on SimWalk2 for an example.


• Enhancement: R-graphics scripts are now more robust to missing files, incomplete analysis etc. Perl scripts now return an error if it doesn't find the input file, and this error is trapped by the shell script. nplplot() now returns a "FALSE" value if the formatted data file is empty or has some problems. This is trapped by the R-script.


• Enhancement: Mega2 batch file is now more robust to errors such as empty value field, and value lists wich do not contain enough items.

• Enhancement: Option selection for Merlin-only format - The user is prompted to enter a string consisting of Merlin analysis options. For details see the Merlin analysis section.


• Enhancement: Merlin graphics are set up only if either or both the --npl and --pairs options are selected, and the --markerNames option is not selected.


• Bug-Fix: Fixed S.A.G.E. 4 parameter file bug in the format statement.


• Bug-Fix: Fixed S.A.G.E. 3 counts parameter file bug in the format statement.


• Bug-Fix: Fixed PREST pedigree file bug, all lines were combined into one long line.


• Bug-Fix: Fixed Merlin/SW2-NPL pedigree naming mismatch. This option filed to work because the pedigree names in the Merlin NPL output did not match the names in the SimWalk2 pedigree file.


• Bug-Fix: Pedigree and individual id menu behaviour has been fixed. The different options were not being selected and displayed correctly.


• Bug-Fix: Fixed SPLINK format bug - was writing individual ids in place of mother's ids.


• Bug-Fix: Fixed bug in SimWalk2 for handling more than 100 liability classes.


• Bug-Fix: Fixed bug in the Win 32 version of Mega2, where the locus order line was not read in correctly. The 2.5 version will work correctly however, al lomg as there is an extra non-numeric character before the newline.


• Bug-Fix: Blank lines are allowed before the locus-order line again, the check for locus order in Ver 2.5 did not accept blank lines just before the locus order line.

• Enhancement: New option for creating Loki-format files.


• Enhancement: New Recode utility for converting a minimal locus data file with only locus types and names as input, then creating a linkage-format locus file with allele frequencies computed from the pedigree data.


• Enhancement: New batch file options for greater automation
  Default_Outfile_Names
  Default_Reset_Invalid
  Default_Other_Values
  Default_Ignore_Nonfatal
  Default_Ignore_Xlinked
  See Batch file documentation for details.


• Enhancement: R-plot labels for each curve can now be input separately from a header file. Mega2 creates this header file by default, and instructs the nplplot() routine to skip the first line of the input plot data file.


• Bug-Fix: in SOLAR where the phenotype file and marker genotype file didn't match the person ids in the pedigree file (id choice was not implemented for the former).


• Bug-Fix: in locus reordering, for multiple chromosomes and multiple traits, traits were being output at the beginning of the order irrespective of the user's ordering.


• Bug-Fix: in selection of loci for random genotype error detection from the batch file.


• Bug-Fix: in renaming chromosome number extension for output files.


• Bug-Fix: for segmentation fault for 0 recombination fractions (where there is only a single locus in premakeped-format output files.


• Bug-Fix: existing vstrm files are removed before each Vitesse run.


• Enhancement: Flag too few locus numbers in locus order line of input linkage-format locus file.


• Enhancement: Creating a marker frequency file for Merlin-format.


• Enhancement: Improved user-interface for selecting pedigree and indvidual id for output files, these can be either selected from the input, or generated in some cases, e.g. unique ids can be generated by mega2.


• Enhancement: Changed y/n user-prompt for per-chromosome files in various options to a numbered menu (with separate files as the default).


• Enhancement: Menu for selecting Allegro scores to plot now have more descriptive names.


• Enhancement: R-setup menu called only once for the SimWalk2-Merlin interface option.


• Enhancement: For Merlin, cannot handle generating plots for multiple traits if they are combined (each trait separately works).

• Bug-Fix: SimWalk2 penetrance file had invalid liability class values. Acceptable values are 1-99. Currently, if the input data has affection loci with 100 or more classes, Mega2 will produce a penetrance file that is not acceptable to SimWalk2. Efforts are underway to modify SimWalk2 to accept a larger numbe of liability classes.


• Bug-Fix: SPLINK option produced garbled individual ids in the pedigree file if the user opted to combine all loci into one pedigree file. This has been rectified.

• Bug-Fix: For SOLAR, the HHID phenotype was being written into the phenotype file, this has been moved to the pedigree file.


• Enhancement: Number of allowable liability classes has been increased upto a million. Theoretically, there really is no limit, except for Mendel-format output which has a field size limitation.


• Enhancement: New MEGA2.KEYS file now gives a mapping to pedigree and person ids between the input and output.


• Bug-fix: Fixed major bug in loop reconnection - the older version assumed that the proband numbers were ordered in the pedigree file. Also, the renumbering of links (first_off, sibs etc.) was off. For each loop-reconnection pair (delete_person, keep_person), we have to follow two steps:
  1) Look at each occurrence of delete_person and change it to the corresponding keep_person.
  2) Then look at the links fields of keep_person, and make sure they match the delete_person's fields.
  


• New analysis option: Merlin 0.9.x format files merlin_ped.01, merlin_data.01, and merlin_map.01.


• Changed the Merlin files for Simwalk2-Merlin option to sw2merlin_ped.01, sw2merlin_data.01 and sw2merlin_map.01.


• Bug-fix: Fixed individual-count for pre-makeped format input pedigrees.


• Enhancement: Sex-specific map positions in the map file, This requires the two words, "male" and "female" in the header line of the map file AFTER the first three columns. The type of map (kosambi or not) is decided by the title of the sex-averaged distance column.


• Enhancement: Several options can now select which pedigree id to output (Ped: or linkage id) and which person id to output (Per:, linkage or ID:). If these fields (at least the Ped:, Per: and ID:) don't exist in the input they are generated, and the user is informed of the fact. These options are Simwalk2, Mendel, Aspex, SAGE, SOLAR, Genotyping Summary, Pre-makeped, Merlin-SimWalk2, and Merlin. Refer to Using unique person ids for details.


• Bug-fix: Selecting only trait loci in S.A.G.E. 4.0 resulted in a segfault. This has been fixed.


• Minor bug - Menu wording in SimWalk2 file names menu was a bit strange, so changed the wording.

• Bug-fix: Versions 2.3 and 2.3 R1 may have had a segmentation fault when creating nuclear pedigrees from post-makeped pedigrees which did not have person ids numbered consecutively from 1 thorugh the number of pedigree members. Nuclear pedigrees are also created in the S.A.G.E. 3.0, ASPEX, and GHMLB options. Pre-makeped pedigrees do not cause segmentation faults in either version 2.3.


• Bug-fix: Post-makeped pedigrees with non-ordinal entry ids may have also created segmentation faults in the "create summary" option for segregation summary. Again pre-makeped files are not a problem.


• Bug-fix: Mendel pedigree file format statement has been fixed. The format statement for reading in pedigree members was incorrect.


• Enhancement: A totals line has been added to the affected sib count section of the sib_sum.* file.


• Enhancement: In addition to chromosome-specific genotyping success rates, an overall genotyping-success rate file is created (if analysis includes multiple chromosomes).


• Bug-fix: The script sage_cnt.*.sh was not working in case of a single affection trait. This script has been corrected.


• Bug-fix: In some cases, nuclear families included half-sibs This bug affects Aspex, Affected Sib Counts, GHMLB and S.A.G.E.

• Removed a bug from the loop-reconnection process. Mega2 failed to reconnect loops if pronad number 1 did not appear before all other probands in the post-makeped format pedigree file.


• A mistyping simulation option can be activated via the first menu, so that random genotyping errors according to an error probability distribution is introduced within the known genotypes. Currently, there are 3 models, uniform (across all markers), uniform within each specific marker, and the SimWalk2 error model.


• Added a batch file which will automatically fill most user input upto the analysis-specific menus. See the Mega2 Batch section for details.


• PREST analysis option - Relationship estimation


• PAP analysis option


• Simwalk2/Merlin interface option for NPL This creates two sets of data files, Merlin-format files and Simwalk2-format files with a modified npl.sh script that first executes Merlin, then feeds Merlin's p-values into Simwalk2. See documentation for more details and on how to use this option.


• SimWalk2 graphs: For Simwalk2 - NPL, we can now create an R script to plot the LOD scores and store them in a postscript file. There are user menus to set options for these plots.


• Allegro graphs: We have added an R script for graphing Allegro results.


• The analysis menu is changed in appearance, it is in two columns with slightly different analysis names in order to accommodate the additional analysis options.


• We now allow an additional field (:ID) in the input linkage-format pedigree file as well as pre-makeped format pedigree file. The post-makeped file can also contain the :Ped and :Per fields in addition to the :ID field.


• Linkage-format now warns if there are "real" phenotypes which are 0.0 which is the default "unknown" value in Linkage.


• Mega2 was computing the biased (population) std-dev value, this has been changed to the unbiased (sample) std-dev.

• For X-linked markers, Mega2 Version 2.2 R2 was incorrectly finding inheritance errors that weren't really there. This has been fixed.


• New allele frequency summary format: now the histogram is drawn along with the table. For sex-linked markers, we have an overall table without histograms, then the sex-specific tables with histograms.


• SAGE 3.0 option was buggy, the formats of the fsp and fcor files were incorrect. The shell file did not work correctly. New implementation now has correct formats. Handling of multiple trait loci is improved: Excerpt of mega2 message from reordering-traits menu: "If multiple affection status loci are selected, FCOR files will be set up in trait sub-directories. SIBPAL files will be set up in the main directory If multiple QTLs are selected, FCOR and SIBPAL files will be set up in the main directory." Other changes include elimination of "no match" messages from the "rm" command inside the shell files. In general, this option has undergone major re-vamping. Also, if there are QTLs only, the file-names menu does not ask for sage_cnt and cntpar file names. The list of files displayed as created at the end of a run also match this behaviour.


• Mega2 LOG file has more details on the run options such as Mega2 version number, pedigree omission criteria, analysis option etc.


• Half-types have to be compulsorily set to 0/0 for Mendel and Simwalk options, so the reset-option menu is not ppresented to the user if Mega2 detects half-types, instead a notification is printed.


• Mega2 exits if no loci are selected via option 2 reordering.


• Mega2 now checks for empty input files in addition to DOS files. It terminates with an error message.


• For ASPEX, Simwalk and Sage4 options, the marker order is checked for negative intervals (only for user-input order). Files are created with a warning.


• The log and error files were being appended to instead of overwritten. This has been rectified.


• Mega2 crashed if no marker loci were selected, this has been corrected.

• Expiry date checking has been fixed.


• Checking for too many alleles within a sibship produced spurious error messages bacause it did not handle half-siblings properly. It now only checks full siblings.


• Menu for resetting genotypes has been fixed, the EXIT option did not work roperly, it failed to terminate Mega2.

• Partial ordering of individuals inside a pedigree that simply makes sure that parents are numbered lower than offspring instead of the more rigourous sorting that was being used (tried to sort uncles half-siblings too), which caused infinite loops for highly inbred pedigrees.


• Added a new simwalk2 option called Mistyping analysis, in anticipation of the release of SimWalk2 version 2.82.


• Other minor changes in the batch file for Simwalk2.


• Added check for DOS-format input files, Mega2 exits with a message if any file is a DOS-format file.


• Better detection of Mendelian inconsistencies in the presence of untyped parents.


• User has the option of specifying which set of invalid genotypes to set to (0,0), half-typed, Mendelian inconsistencies, neither or both. So the "Inconsistencies found - how shall we proceed" menu looks a little bit different now.


• Fixed SLINK to handle QTLs properly - does not ask about affecteds if trait chosen is a QTL.


• More information about unconnected components of a pedigree is displayed, consisting of some of the individuals that make up the pedigree.


• Fixed bugs in how Mendel handles a set of loci with only QTLs.


• Fixed handling of allele_count option for untyped markers, these are skipped as they should be.


• Corrected shell file headers for ASPEX and SPLINK.

• Bug found and fixed in SPLINK whereby a space was missing betwen the affection status locus and following data.


• Added affection status definition menu inside the SPLINK option, since SPLINK does not handle multiple liability classes.


• More informative error messages for input Pedigree files.


• Fixed string overflow problem where the long version of output option name is stored.


• Further fix to Vitesse Linkmap files, ordinal locus numbers are NOT used anymore, so that the program "map" can create a composite map from several windows analyzed by Vitesse Linkmap option.

• Bug in Vitesse LOG and STM files, the loci numbers and names were incorrect. These are generated correctly now.


• Bug in ASPEX sib-phase graph scripts for the theta grid option, the files gph.*.*.*. files did not have the proper curve data. This has been fixed.


• Added some checking in Vitesse that verifies user-input interval size inside Linkmap. If input consists of a single chromosome, this is checked within the Linkmap inteerval menu, otherwise, it is checked during the processing of each chromosome. If there are fewer markers on any chromosome than the reqquested interval size, the user is given the opportunity to define a smaller size for that chromosome, the original length is used for chromosomes that have the requisite number of markers.


• Bug in Output linkage-format files (Genehunter options, SLINK, Vitesse etc.), the affection status and liability class columns ran into each other. They are separated with a space now.

• Added support for pre-Makeped files.


• Automatic loop-breaker selection for options that need post-Makeped pedigree files.


• Multiple marriages are allowed, and one loop-breaker can break more than 1 loop.


• Added support for Allegro, MLBQTL and S.A.G.E. 4.0 formats.


• Map files with kosambi distances are allowed.


• Original person ids can be output in Mendel and Aspex output files, if provided in the post-Makeped format pedigree file.


• Untyped pedigree omission options to specify minimum number of genotyped individuals in a pedigree for it to be included in the output.


• Easier way to select loci in option 2 of locus reordering menu by specifying a range e.g "1-10". Ranges can be interspersed with specific locus numbers each separated by whitespace (eg 1-5 9 11 12-15).


• Handling of multiple trait loci, where the analysis option allows such data. Otherwise, selection of multiple traits causes separate sets of output files to be produced for each trait.


• Improved handling of QTLs. Now has checks to see that QTLs are included in output only if the analysis option allows them.


• Simwalk2 batch file now uses   !  as the comment character instead of   => .

In addition, several bugs from the previous version have been fixed, and Mega2 is more robust to errors in input files, as well as in user responses. For the user's convinience, Log and Error files are created for each run.