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COVER.ME
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Dear Colleague,
Welcome to MAPMAKER.
MAPMAKER is an interactive computer package for constructing genetic
linkage maps, and for mapping genes underlying complex traits using
those linkage maps. The current version of the MAPMAKER package
contains the following two programs:
MAPMAKER/EXP is a linkage analysis package for constructing primary
linkage maps of markers segregating in experimental crosses.
MAPMAKER/EXP performs full multipoint linkage analyses (that is,
simultaneous estimation of all recombination fractions from the primary
data) for dominant, recessive, and co-dominant (e.g. RFLP-like) markers
in BC1 backcrosses, F2 and F3(self) intercrosses, and Recombinant Inbred
lines. MAPMAKER/EXP is an experimental-cross only successor to the
original MAPMAKER package.
MAPMAKER/QTL is a companion program to MAPMAKER/EXP which allows one to
map genes controlling polygenic quantitative traits in F2 intercrosses
and BC1 backcrosses relative to a genetic linkage map.
The first version of MAPMAKER was distributed in 1988, while
MAPMAKER/QTL appeared in 1990. Since then, we have had many occasions
to revise our in-house version of the programs based on our experiences
using it on our own data sets. Recently, we decided that enough
worthwhile additions had been made to justify issuing the third major
public release, MAPMAKER/EXP Version 3.0 and MAPMAKER/QTL 1.1. Some of
the major changes that may be of interest:
* MAPMAKER/EXP understands more types of experimental crosses.
* MAPMAKER/EXP incorporates an algorithm for detecting potential
genotyping errors, as described in Lincoln and Lander (Genomics 14:
604-610, 1992).
* Many features have been added to allow automatic analysis of very
large data sets. A new three-point analysis feature helps make these
big jobs much faster. A "join haplotypes" feature helps efficiently
handle recombinationally unseparated markers.
* User interface improvements include the ability to draw chromosome
maps and QTL LOD plots as PostScript graphics, as well as a command
line editing feature.
* Both programs have had many bugs fixed and have a number of subtle
feature improvements. For example, locus names now work correctly in
all parts of both programs. A "change list", is included which lists
many of these modifications.
* The license agreement for the MAPMAKER package has been changed to
allow free redistribution. That is, you are welcome to copy the copy
the programs from your colleagues and for your colleagues. Moreover,
under specific conditions, you may distribute modified versions of
MAPMAKER. See the license agreement for details.
* A great deal of effort has been put into making MAPMAKER work
correctly on PC-compatible computers under DOS as well as Macintoshes
(although only under Unix).
A note on the history of these programs:
MAPMAKER/EXP:
Several years ago, we worked out, together with Phil Green, an efficient
algorithm for multi-point linkage analysis in CEPH-type pedigrees. To
compute the map distances for one genetic order, the computation time of
this algorithm scales linearly (rather than exponentially) with the
number of loci being studied. We implemented this algorithm in a
computer program and found that it allowed us to study large numbers of
loci in manageable amounts of time.
As we began to analyze large data sets, however, we realized that our
job was less than half-done. In addition to being able to construct the
maximum likelihood map for any given order of markers, we needed a
computer package that would let us conveniently explore and compare many
alternative possible genetic orders. This was not necessary for data
sets consisting of five or six markers, but was essential for projects
involving dozens or hundreds of loci. Thus, we set out to build a
"geneticist-friendly computer environment" for exploring data and
building linkage maps. The result was MAPMAKER.
Much of the heaviest use of MAPMAKER has been in analyzing experimental
crosses. MAPMAKER/EXP represents our first version tailored
specifically for data from experimental crosses. We hope to fold new
features into a future version for handling outbred crosses in a
complete manner, although no such features exist at present (some types
of outbred crosses can still be analyzed by MAPMAKER however, see the
"Preparing Data" document for details. For those who require CEPH-type
data analysis, version 2.0 of MAPMAKER, including this capability,
remains available by FTP.
Multi-point linkage analysis considers all of the raw (genotypic) data
available simultaneously in each computation to find map orders and map
distances. We contrast this with so-called "multi-two-point" approaches
which consider many pairwise relationships between markers at once, but
not the raw data itself.
MAPMAKER/EXP 3.0 carries these ideas further, as it is the computer
program we have used for assembling our lab's genetic map of the mouse
(currently at over 1,000 loci scored on 46 F2 intercross progeny).
MAPMAKER/QTL:
The availability of high-resolution molecular genetic maps has made it
feasible to understand the underlying genetic and biochemical basis of
many traits displaying complex modes of inheritance. To accomplish
this, together with David Botstein, we worked out a maximum likelihood
algorithm for mapping the genes underlying quantitative traits
segregating in experimental populations. Using this method, we have
looked at traits including hypertension, cancer, and diabetes in rats
and mice, while in agricultural genetics we have examined yield, disease
resistance, and quality characters in a variety of crop species and
agricultural animals.
MAPMAKER/QTL is our computer program for mapping these genes using the
techniques of "interval mapping" and "simultaneous search". Interval
mapping uses the power of a complete genetic map to discern weak effects
from genetic distance between marker locus and putative QTL
(Quantitative Trait Locus), while "simultaneous search" allows us to fit
multiple QTLs across the genome at once, thus reducing the overall non-
genetic variance in the trait. Both techniques together provide
increased "power" for detecting QTLs, allowing one to find genes with
smaller effects (in equivalent data sets) than one can using simpler
phenotype on genotype correlations. MAPMAKER/QTL uses data sets
(including maps) prepared by MAPMAKER/EXP.
The Manual:
The best way to learn about a computer program is to use it. We have
therefore written two tutorials which demonstrate the use of MAPMAKER
and MAPMAKER/QTL, respectively. The sample data set on which the
tutorials are based is included with the software, so that you can sit
down at the computer and try various analyses out as you read the
tutorials.
Following the tutorials, the reference sections describe in more detail
the various commands, including many commands not mentioned in the
tutorials but which you may find useful over time. These descriptions
are also available on-line, via the "help" command.
Subsequent sections of this introduction describe how to prepare data
for use by the MAPMAKER programs and how to install the programs on your
computer. (MAPMAKER is designed to run on either Unix based computers,
such as Sun workstations, or on high-end PC compatible computers running
DOS or Microsoft Windows). The release notes also detail the License
Agreement and provide instructions for requesting the software,
reporting problems, or retrieving the source code (which is in "C").
A warning: While we have tested the programs extensively on our own data
and on our computers, there will almost certainly be small bugs that we
have not turned up. We urge you to inform us about the problems so that
we may fix them. Even better, for those groups with programming
expertise, if you can fix any bug, port the software to some other type
of computer, or extend its functionality, please send the modifications
on to us. We will either incorporate them into the distributed version,
or at least make them available as "user contributed" code.
The initial MAPMAKER program was the result of the extraordinary efforts
of Stephen Lincoln, Mark Daly, Jeff Abrahamson, Aaron Barlow, and Lee
Newburg. The new version of MAPMAKER, the extensive documentation, and
all of the development of MAPMAKER/QTL have been the brainchild and
product of Stephen Lincoln and Mark Daly. I am extremely fortunate to
be associated with such talented scientists and programmers.
Finally, MAPMAKER is distributed freely to both academic and coprporate
researchers. However, this work is quite expensive and time-consuming.
Coprporate users who bennefit from these programs are encouraged to
contribute a donation in lieu of payment, solely to help with the
ongoing support, development, and distribution of the package (tax-
deductable donations may be sent to the Lander Lab at the Whitehead
Institute). Researchers are further encouraged to cite MAPMAKER in
papers and talks when the package has been of use.
Happy mapmaking!
Eric S. Lander
January, 1993