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linkage newsletter

Mon Feb 14 16:41:03 EST 1994

                       Linkage Newsletter

                  Vol. 8   No. 1   January 1993

Published by Jurg Ott, Columbia University, New York

Editorial Assistant:  Katherine Montague
     Fax: 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


     Our newsletter, now in its eighth year, is sent to many
hundred recipients world-wide.  More and more people receive it
by e-mail, but we are still sending several hundred copies by
postal mail.  Please, if you receive this by postal mail, send us
your e-mail address if possible - we would like to further reduce
the labor intensive task of sending the newsletter by postal
mail.  If you are afraid of not receiving the newsletter by e-
mail, we can send you a test message, or you may ask us to send
you the newsletter twice, or to different e-mail addresses.


     The next two linkage courses are Introductory Courses.  They
will take place as follows:
     June 6-10, 1994, at Columbia University, New York (maximum
of 30 participants), and
     June 13-17, 1994, at the University of Zurich, Irchel Campus
Computer Center (Switzerland;  maximum number of participants is
     These courses are for researchers with little or no experi-
ence in using linkage programs.  A basic knowledge of linkage
analysis is, however, required.  Topics:  Introduction to linkage
analysis;  practical aspects of data collection;  strategies and
methods of linkage analysis;  incomplete penetrance;  inbreeding
loops;  simple risk calculations;  introduction to computer
simulation.  As usual, the main focus will be practical exercises
and linkage analyses carried out by the participants on IBM PC's
using the LINKAGE and other programs.  Each session will begin
with a theoretical introduction on the material to be worked on.
We will use our new book as the course textbook instead of
mimeographed handouts (Terwilliger and Ott, "Handbook for Human
Genetic Linkage," Johns Hopkins University Press, to become
available in May 1994).


(Contributed by Dr. Pericak-Vance)

                  COURSE ANNOUNCEMENT
     Description:  A four day intensive course on mapping
     human genetic diseases.  The concentration is on the
     entire disease mapping process, including clinical
     classification, pedigree collection, molecular
     genetic analysis, statistical analysis, and gene
     characterization.  The emphasis is on the global
     decision-making process, rather than details of
     specific techniques.  Participants will be expected
     to discuss their own research projects.

     Date and Location:  May 15-18, 1994
                         Duke University
                         Durham, NC

     Deadline for completed application:  March 1, 1994.

     For information     Dr. Margaret Pericak-Vance
     contact:            Division of Neurology, Box 2900
                         Duke University Medical Center
                         Durham, NC 27710
     or E-MAIL:          genclass at genemap.mc.duke.edu


(Contributed by Dr. A.W. Eriksson)

     On April 22 and 23, 1994, the International Symposium 'Gene-
     tic Epidemiology of Twins & Twinning' will be organized at
     the Free University in Amsterdam, The Netherlands.  At this
     symposium two main issues will be addressed.  First, causes
     and consequences of the recent epidemic of multiple gesta-
     tions as well as the possibilities to repel current high
     multiple birth rates.  Second, twins as a methodological
     instrument in genetic epidemiology and behavior genetics.

     For information     Bureau PAOG-Amsterdam
     contact:            Tafelbergweg 25
                         1105 BC Amsterdam
                         The Netherlands
     Tel: 31-20-566 4801 Fax: 31-20-696 3228


PC version 5.2 of LINKAGE

     Two bugs were reported to me by Drs. Ken Morgan (McGill U.)
and Marcella Devoto (Columbia U.).  Both resulted in wrong lod
scores in a LINKAGE program that seemed to run fine otherwise.
The first bug was fixed by Dr. Mark Lathrop;  the updated LINKMAP
program is being mailed out since about November 1992.  The
second bug is caused by an overflow of an integer variable in
Turbo Pascal, where integers are only 2 bytes long.  Until a
better solution can be found, the problem may be cured by the
statement, TYPE integer=longint, at the beginning of the Turbo
Pascal LINKAGE programs (this has been implemented in the cur-
rently mailed versions).

Turbo Pascal versions of SLINK and TLINKAGE

     The Prospero Pascal compiler for a while seemed a good
choice for PC's because it can generate code to run under DOS or
OS/2.  Because of availability problems and because it does not
seem to do well with version 5.2 of LINKAGE, we are converting
all our Prospero Pascal programs to Turbo Pascal (for DOS) and
NDP Pascal (for OS/2).  For a few weeks now, we have been mailing
Turbo Pascal versions of SLINK and TLINKAGE.  We just became
aware of problems with these program versions.  These programs
are based on earlier LINKAGE versions, in which some dynamically
allocated arrays had not been initialized.  We have now taken
corrective action - if you are experiencing problems with your
Turbo Pascal version of SLINK or TLINKAGE, please let us know,
we'll gladly send you an amended version.

     SLINK will soon be available in a fast version.  Drs.
Alejandro Schaffer and Daniel Weeks have incorporated some of the
features of FASTLINK in SLINK.  More information will be avail-
able in the next Newsletter.

Turbo Pascal for OS/2?

     An article in the German computer magazine -ct- reported on
a rather easy patch to Turbo Pascal with the effect that code
generated will run under OS/2.  I do not yet know much more about
this interesting possibility but hope to be able to provide
detailed information in the next Newsletter.  If anyone has
experience with this, please let us know so all linkage analysts
can profit from it.

Two potential problems with NDP Pascal

     End-of-file character:  In DOS, the character with ASCII no.
26 (Ctrl-Z) serves as an end-of-file mark.  Our OS/2 NDP Pascal
version, however, does not recognize this character and its
function in DOS, rather it treats it just like any other charac-
ter.  This creates a problem in pedigree input files for which
the LINKAGE programs apply an end-of-file test too see whether an
input line is the last line in the file.  If Ctrl-Z is present on
the next line, the end-of-file test is "false" and the program
attempts to read another input line (a pedigree number).  It then
issue the error message "invalid real" and aborts.  Obviously,
the problem may be overcome by removing the Ctrl-Z character
before the file is used by the LINKAGE programs.  Neither PREP-
LINK nor MAKEPED append a Ctrl-Z but, unfortunately, both editors
supplied with OS/2 do.  Thus, if you modified one of the input
files for the LINKAGE programs with an OS/2 editor, you must
remove the trailing Ctrl-Z character.  This may be achieved by
using an editor that does not append a Ctrl-Z, for example, DOS
EDIT or the old WordPerfect Program Editor.  If you use DOS EDIT,
press Ctrl-End to move the cursor to the end of the file - the
cursor should then be at the beginning of the line immediately
following the last input line.  If it does not, press the back-
space key as often as necessary until the cursor is at the end of
the last input line (on that line);  then save the file.

     Numbers with preceding 0's:  Most Pascal programs read a
number such as 023 simply as 23.  Not so  programs compiled with
NDP Pascal.  They treat numbers with preceding 0's as octal
numbers.  For example, 023 is interpreted as the decimal number
19.  Numbers with preceding 0's that contain 9's are interpreted
as 0.  Consequently, if two pedigrees carry the ID numbers 08 and
09,  they will in NDP Pascal programs wind up with the same ID
number (that is, 0).  We have thus added a small program to the
MAKEPED batch file.  It replaces the first 0 in a pedigree ID by
P0.  That way, pedigree ID's are treated by MAKEPED as characters
rather than numbers, and the pedigree ID's output by MAKEPED are
simple numbers.

LSP for the DOS version of CLINKAGE

     As reported over a year ago, for the CEPH families version
of the LINKAGE programs (eg. CILINK), the LSP program created a
faulty datafile when the number of loci was larger than about 20.
This problem has now been resolved by Ms. Xiaoli Xie - it was due
to an inappropriate array bound in LSP.

LCP and LSP for OS/2

     The OS/2 versions of LCP and LSP until recently ran only in
full screen mode.  If a user started one of these programs in a
window the screen temporarily switched to full screen until the
program finished.  Ms. Xie has now made these programs window-

Support through grant HG00008 from the National Center for Human
     Genome Research is gratefully acknowledged.

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