Linkage Newsletter
Vol. 7 No. 1 February 1993
Published by Jurg Ott, Columbia University, New York.
Editorial Assistant: Katherine Montague
Fax: +1-212-568-2750 Tel. 212-960-2507
e-mail: ott at nyspi.bitnet or jurg.ott at columbia.edu
Postal address: Columbia University, Unit 58
722 West 168th Street, New York, NY 10032
Support through grant HG00008 from the National Center for Human
Genome Research is gratefully acknowledged.
EDITORIAL
As linkage analysts buy more and more powerful computers
they also try to run larger problems than before. Under MS-DOS
on a PC, one often runs into restrictions imposed by DOS or Turbo
Pascal such that no analysis or only an approximate analysis is
possible. We keep trying to improve this situation for PC users.
The 80486 machines are now quite powerful and it is more a matter
of using appropriate software to tap the full potential of these
machines. We now have considerable experience with OS/2 and to a
lesser degree, with Windows 3.1. OS/2 version 2 clearly seems
the more stable platform, particularly now that Corrective
Service Diskettes are available from IBM, which eliminate prob-
lems encountered in the original version 2 of OS/2.
We started using the NDP Pascal compiler from Microway (see
advertisements, for example, in BYTE magazine, Feb. 1993, page
160) and are impressed with its potential. It has none of the
restrictions that plague users of Turbo Pascal and, to some
degree, also of Prospero Pascal. The company is very responsive
to inquiries, which unfortunately seems less the case for the
makers of Prospero Pascal in England. Currently, only a beta
test version of NDP Pascal is available for OS/2 but the full
version might be on the market by the time you read this.
We are also in the process of porting the LINKAGE programs
to Windows under Borland Pascal version 7. However, Borland
Pascal has restrictions similar to those of Turbo Pascal except
that presumably, much more memory can be allocated under
Windows than under DOS. On the other hand, arrays still cannot
exceed 64KB in size, etc.
Among other developments at Columbia, we are working on
setting up an anonymous ftp site for program distribution. Also,
programs will be available not only for DOS but also for Unix and
VMS machines (see below for some existing ftp sites).
LINKAGE COURSES
Due to time constraints, no introductory linkage course
could be scheduled in Zrich for this spring. However, the
following two courses will be held in 1993:
New York (introductory course), at Columbia University: May
17-21, 1993.
Zrich (advanced course), at the Computing Center of the
University of Zrich Irchel campus: September 27 - October 1,
1993.
Registration is open for both of these courses. For infor-
mation and application forms please write to the address above,
preferably by fax. The Columbia University Advanced Course for
the academic year 1993/4 will be held in January of 1994 but a
date has not been fixed yet.
HINTS FOR INSTALLING AND USING OS/2
The following experiences with setting up OS/2 may be useful
to the readers of the Newsletter.
On many machines other than IBM's, it is preferable to make
changes to the BIOS before installing OS/2. In our experience
the most important point is that an external disk cache be
disabled (OS/2 provides its own disk cache, which works well).
Also, installation is easiest when you allow the installation
program to format the hard disk while it installs OS/2. If you
want to install OS/2 without reformatting the hard disk, the
following steps are recommended: 1) Make a boot disk (floppy)
for DOS and try it out; that is, you must be sure you can boot
DOS from the floppy drive. 2) Delete any unneeded files. 3)
Remove all file fragmentation and make all files contiguous on
the disk by using, for example, the Norton SpeedDisk program (use
full optimization). 4) Turn off your computer, insert the OS/2
installation disk, and turn your computer on again.
The program will ask you whether you want to install every-
thing or only a selection of features. I would choose the
latter. For example, I would NOT install fonts or games. This
way you only require approximately 25MB of disk storage for the
system. As you select and deselect features, the program dis-
plays how much space is available on your disk and keeps a
running tally of how much disk space is required for the current
selections.
A major decision is whether you want to use the high perfor-
mance file system (HPFS) or the old-fashioned file allocation
table (FAT) system. For compatibility with other programs,
particularly when you want to boot native DOS, FAT is preferable
although it suffers from the well-known problem of file fragmen-
tation. Once you use OS/2, you may occasionally encounter a
problem with extended file attributes that OS/2 uses but DOS does
not. For example, you may be unable to delete a file because it
is cross-linked with another file's extended attribute. There is
an easy solution: just run OS/2's chkdsk program as often as is
required to get rid of the problem. Some of these problems
cannot be fixed by chkdsk if OS/2 was booted from the hard disk
(as is usually the case). Then, shut down OS/2 (keep the cursor
on a free space of the Desktop and press the right mouse button),
put the OS/2 installation disk into the A: drive, and reboot.
After you insert the second floppy (disk no. 1), press Esc when
the program asks whether you want to continue installing. You
are then left with a working version of OS/2 and should see the
prompt, [A:>]. Now, enter, for example, C:\OS2\CHKDSK D: if your
OS/2 system resides on the C: drive and you want to check prob-
lems on the D: drive. Alternatively, insert disk no. 2 of the
installation package (it contains chkdsk.exe) into the A: drive
and enter A:CHKDSK D:. You may need to issue this command
repeatedly until chkdsk no longer reports a problem (it seems to
fix only one problem at a time).
You may switch between various DOS and OS/2 windows.
However, be aware that whatever windows are open consume a
certain amount of RAM, which is lost to other windows. Also, the
DOS windows by default have 2MB of extended and expanded memory
each, which is usually much too much. To adjust these settings
for a given DOS window, first exit from this window (it must not
be active), then click on its icon using the right mouse button.
A small window appears, which says "Open" at the top. With the
left mouse button, click on the arrow in that row (be sure it's
the arrow). Then click on Settings, then on Session, and then on
DOS Settings. The most important DOS settings to change are
EMS_MEMORY_LIMIT and XMS_MEMORY_LIMIT. Also, if you want to
operate a modem from this window (it is best to reserve one
window for running your communications program such as Kermit),
set IDLE_SENSITIVITY to 100; this will ensure smooth operation
of your communications program. Note that these changes cannot
be made on a window while it is open.
Under OS/2, one has even more control over programs running
in a DOS window than when they run under native DOS. For exam-
ple, if a program is caught in a loop and you are unable to
interrupt it, you can simply close the window in which it is
running. Under DOS or Windows 3.1, one must reboot the machine.
In our experience, there are very few DOS programs that do
not work properly in DOS windows of OS/2. Some of the newest
Norton Utilities do not work properly (but FileFind and FileSize
work fine). To occasionally use such programs, one simply boots
the machine under DOS from a floppy disk.
While OS/2 emulates DOS version 5 very closely, we have
found one difference thus far: Backup and Restore are different
enough that files backed up in a DOS window under OS/2 cannot be
restored under native DOS, and vice versa.
The current OS/2 version supports Windows 3.0. We have
successfully installed several Windows programs in this "Windows"
version. One program, SYSTAT, does not work properly this way
although it works fine under regular Windows 3.1.
SOFTWARE NEWS / BUG REPORTS
== Version 5.2 of LINKAGE ==
Mark Lathrop has released version 5.2 of LINKAGE. The new
programs are available from Mark Lathrop and will soon be avail-
able from us. We are presently running some tests. Preliminary
benchmark runs (see Linkage Newsletter, May 1991) show the
following results (times given in seconds for two likelihood
calculations, run on an 80486 25MHz):
Version 5.1 Prospero and Turbo Pascal DOS 121 sec.
Version 5.1 NDP Pascal OS/2 71 sec.
Version 5.2 NDP Pascal OS/2 71 sec.
Line 1 versus 2 shows the greater efficiency of NDP versus
Prospero and Pascal. Line 3 says that, for our benchmark data
set, the new version is about as fast as version 5.1; it may,
however, be faster for other data sets.
Incidentally, we also ran the benchmark data set using the
MENDEL program. It was compiled with Microsoft Fortran 5.1 such
that it ran under DOS or OS/2. Because of the array sizes, which
are required by MENDEL for the given data set, MENDEL was unable
to run under DOS. Under OS/2, it required approximately 12MB of
RAM to run and took 1298 seconds to complete (run on an 80486
with 16MB RAM to prevent usage of virtual memory). The MENDEL
program can thus be quite slow in the presence of many untyped
individuals. On the other hand, it is more flexible than LINKAGE
in the problems that a user can address.
In this context, the time requirements for the benchmark
data set on three other machines are of interest (reported by
Iain Fenton, Cardiff). The following times represent elapsed
time, not CPU time:
DEC 5830, running Ultrix 4.2, 3 CPU's, 128 MB memory (with ap-
prox. 50 interactive users) 40 sec.
DEC VAX 6000-400 cluster, running VMS 5.4, 2 CPU's, 96+32 MB
memory (with approx. 20 users) 96 sec.
Viglen VigI, running MS-DOS 3.30, 9.54MHz 8086, no numeric copro-
cessor, 640K memory 6.8 hours
== Sensitivity Analysis Programs ==
(contributed by Dr. Susan Hodge)
SENSEN and SENPED are short Fortran programs designed to facili-
tate basic sensitivity analyses of families, as described in
Hodge and Greenberg [1].
SENSEN takes a standard LIPED input file with data for one family
and prepares equivalent LIPED input files, reversing the affect-
edness status at the main trait for each family member, one at a
time.
SENPED takes the lod file output of LIPED runs on all the sensi-
tivity files for a single family (and a single marker) and
creates an input file for the Pedigree/Draw program [2], showing
the original lod score and the difference in lod score caused by
each change in affectedness status.
SENSEN and SENPED are available from
David A. Greenberg, Ph.D.
Department of Psychiatry, Box 1229
Mt. Sinai Medical Center
1 Gustave Levy Place
New York, NY 10029
e-mail: miriam at onion.salad.mssm.edu
----------------------------------------------
[1] Hodge SE and Greenberg DA (1992): Sensitivity of lod scores
to changes in diagnostic status. Am. J. Hum. Genet. 50:1053-
1066.
[2] Pedigree/Draw is a set of shareware programs for the Apple
Macintosh used to prepare genetic pedigrees. For further infor-
mation about this program (and how to obtain a copy), contact:
Paul Mamelka
Department of Genetics
Southwest Foundation for Biomedical Research
P.O. Box 28147
San Antonio, TX 78284
Internet: paul at darwin.sfbr.org
== Iterating on xf/xm in ILINK ==
With only two loci, when both male and female recombination
fractions should be iterated on, ILINK will work in the usual way
with the variables im (male recombination fraction) and R=xf/xm
(female-to-male map distance ratio). There are now two ways of
treating R: as a fixed ratio (the same in all intervals) or as a
variable ratio. With only one interval, it might appear that it
does not make any difference what one chooses, and this is the
case on Vaxstations and on the Sparcstation. On the PC, however,
variable ratio should be chosen. If the female recombination
fraction estimate turns out to be equal to zero, ILINK reports an
incorrect lod score on the PC. In the example that occurred in
one of our courses, the incorrect lod score reported was 0.86,
but with a variable R, ILINK gave the correct lod score of 4.67.
The difference must be due to the way the LINKAGE programs
compute likelihoods under the hypothesis of no linkage. With R
exactly equal to zero, the female recombination rate is evidently
always set equal to zero even under the assumption of no linkage.
== Bug in LSP under DOS ==
With a large number of codominant loci (more than about 15),
when both Allele Numbers and Binary Factors locus types occur in
the datafile, the LSP program produces an erroneous datafile
output. For example, towards the end of the new datafile creat-
ed, there should be a line containing as many recombination
fractions as there are locus intervals; that number is not
right, which will cause a linkage run to abort. The problem does
not occur with the LSP versions on DEC or SUN machines and is
restricted to the DOS version. Peter Cartwright has been looking
into the problem but thus far has not seen a solution to it. We
are planning to compile LSP with different C compilers to see
whether that might cure the problem.
== New programs ==
The programs listed below have recently been developed by
Xiaoli Xie and may be of interest to linkage analysts. For a
detailed description, please ask for our list of programs.
TypeNext implements a special version of the SLINK program.
For a number of untyped individuals in a pedigree, it estimates
which individuals should be typed next to gain the most informa-
tiveness for linkage analysis (Am J Hum Genet 51 (suppl), A197).
VaryPhen varies the phenotype (affected/unaffected) for each
individual and reports the change in maximum lod score (Am J Hum
Genet 47, A205, 1990).
LOOPS checks for undetected loops remaining in the data
after a pedigree file has been processed by the MAKEPED program.
The LOOPS program is now part of the LINKAGE package and is
automatically invoked whenever one calls MAKEPED (Am J Hum Genet
(suppl) 51, A206, 1992).
USEFUL E-MAIL ADDRESSES
We frequently receive requests for information on how to
obtain Unix versions of the LINKAGE programs. The ftp site
mentioned below contains these and other programs for Sun ma-
chines. To download programs using ftp, proceed as follows
(directions taken from document obtained from that site):
ftp corona.med.utah.edu or ftp 128.110.231.1
When prompted to provide a user name, enter "anonymous". As the
password, give your last name. Then, issue the commands
cd pub/linkage/sun
binary
get linkage.tar.Z
quit
This ends your ftp session. On your Sun machine, issue the
commands
uncompress linkage.tar.Z
tar xvf linkage.tar
rm linkage.tar
We also keep getting requests for information about pedigree
drawing programs for the PC. Several programs exist, some have
been discussed in this newsletter. As an example, the PEDRAW
program by Dr. David Curtis (dcurtis at crc.ac.uk) may be obtained
from various anonymous ftp sites such as ftp.embl-heidelberg.de
or ftp.bio.indiana.edu.
