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To: Multiple recipients of list HUM-MOLGEN <HUM-MOLGEN@NIC.SURFNET.NL>
Subject: LITE: Linkage Newsletter
From: Jurg Ott <ott@linkage.cpmc.columbia.edu>
Date: Wed, 13 Mar 1996 10:54:43 -0500

                        Linkage Newsletter
                  Vol. 10   No. 1   March 1996

Published by                                             Postal address:
Jurg Ott, Columbia University, New York     Columbia University, Unit 58
Email: ott@rockvax.rockefeller.edu                   722 West 168 Street
WWW: http://linkage.cpmc.columbia.edu                 New York, NY 10032

Editorial Assistant:  Katherine Montague
        Email:          km165@columbia.edu
        Fax:            212-568-2750
        Tel:            212-960-2507

(this and all previous newsletters are available on our ftp site/Web page)


        After ten years with Columbia University, the "genetic linkage"
group will be moving to Rockefeller University, New York, where a new
Laboratory of Statistical Genetics is being formed.  The move will
take place throughout this summer and will be completed in November of
this year.  A new ftp site and Web page will be set up at Rockefeller
but addresses are not known yet (note Dr. Ott's new email address
above).  They will be posted on our current ftp site/Web page, which
will continue to exist for some time (at least one year).


        The next courses in genetic linkage analysis have been scheduled
as follows, and interested researchers are urged to apply early as our
courses tend to fill up quickly:

        June 10-14, 1996, at Columbia University, New York (basic course,
maximum of 30 participants).
        June 24-28, 1996, at Columbia University, New York (basic course,
maximum of 30 participants).  The second course will be held only with
a sufficient number of applications (which we expect).  Deadline for
applications has been extended to April 8.

        October 7-11, 1996, at University of Zurich, Switzerland (ad-
vanced course, maximum of 12 participants).  Deadline for applications
is August 30, 1996.

        October 14-18, 1996, at Rockefeller University (advanced course,
maximum of 20 participants, with preference to participants at U.S. inst-
itutions and companies).  Deadline for applications is August 30, 1996.

        To obtain information on these courses, please write to Katherine
Montague, course coordinator, by email (preferred) or fax.

        We will use our book (Terwilliger and Ott, Handbook of Human
Genetic Linkage, Johns Hopkins University Press, 1994), with supple-
mental handouts for advanced courses.  Participants are expected to
buy the book and bring it to the course;  in case of problems please
contact Katherine Montague in advance of the course.  A list of
corrections for the book may be downloaded from our anonymous ftp
site, linkage.cpmc.columbia.edu (file corr_ter.txt in directory book).


>> Fortran and Windows 95 <<

        The only Fortran program currently distributed by us is LIPED. 
If compiled with Microsoft (MS) Fortran version 5.10, various compiler
switches allow it to run under DOS, OS/2 and Windows 3.1.  Under
Windows 95, programs compiled for DOS still run in a DOS window; 
however, programs compiled for Windows 3.1 will not run in Windows 95. 
Presumably, for Windows 95 an updated Fortran compiler must be ob-
tained from Microsoft.  If anyone has experience in this matter,
suggestions would be appreciated.

>> OS/2 and Windows 95 <<

        Even though I was an early fan of OS/2 ever since its version 1.1
came out, "market forces" made me decide that we no longer want to
support OS/2 versions of our programs;  these versions are still
available on our ftp site but they will not be updated.  Users with a
need for running large programs may find it convenient to turn to our
programs compiled with NDP Pascal for DOS.  This compiler does not
impose any limitations on array sizes, code or data segments, etc.

>> FASTLINK 3.0P <<
   (submitted by A. Schaffer)

I am pleased to announce that FASTLINK 3.0P is now available.  FAST-
LINK is a faster version of the main programs in LINKAGE.  As of
version 2.3P, FASTLINK runs in parallel on either UNIX multiprocessors
or networks of UNIX workstations.

As with previous versions, the code is available by ftp from:

Login as anonymous, leave full e-mail address as password.
        cd pub/fastlink

If you are a UNIX user:
        get fastlink.tar.Z

If you are a DOS user:
        cd dos
        <retrieve everything in that directory>

If you are a VMS user:
        get README
        get README.VMS
and follow the instructions there for what you need

Retrievers in Europe may find it more convenient to retrieve from the
mirror site at:

The instructions are similar, but instead of:
        cd pub/fastlink   (for softlib)
        cd pub/software/linkage_and_mapping/FASTLINK/fastlink  (for ebi)

Among the improvements in FASTLINK 3.0P (compared to 2.3P) are:

  --    The code runs faster on data sets that have loops or unused
        alleles.  If you used FASTLINK 2.3P, you may have noticed that it
        printed diagnostics when a data set had unused alleles, but it
        did not take advantage of the situation.

  --    UNKNOWN now detects violations of Mendelian rules of inheritance
        in looped pedigrees. It never did this before.
  --    maxhap and maxfem are no longer in the code as constants.  If you
        were resetting maxhap each time and recompiling, you won't have
        to do that any more. If you were setting maxhap unnecessarily
        high to avoid recompiling, you may perceive some speedup.

See the file README.updates for more details on recent code changes in

Some algorithmic aspects of the most recent improvements can be found

        A. A. Schaffer, Faster Linkage Analysis Computations for Pedi-
grees with Loops or Unused Alleles, Human Heredity, to appear.

This paper can be found as paper5.ps at the ftp sites.

Alejandro Schaffer

>> Two problems in LINKAGE programs <<
   (submitted by A. Schaffer)

Two LINKAGE problems have arisen recently in FASTLINK bug reports that
users should be aware of.  I call them "problems" and not "bugs"
because one has to abuse LINKAGE to get them to happen.

Problem 1.  If a loop involves someone who is multiply married, and it
is unbroken, then LINKAGE might not go into an infinite loop.  If it
doesn't, plausible but wrong results are printed.  I have now seen 3
pedigrees with this problem.  This is not a ■bug■ because if one uses
MAKEPED with LOOPS embedded as one should, the loop will be caught

Problem 2.  If an allele frequency is specified as 0.0 various prob-
lems can arise. The one I saw is:
  --    user specified frequency of first allele is 0
  --    data set had a pedigree in which nobody was typed at that locus
  --    unknown converted everyone to homozygous 1 1 at that locus
  --    because the allele frequency was 0.0, the likelihood also came
        back as 0.0, making the log likelihood -infinity.

Both problems are also present in all versions of FASTLINK until the
most recent (3.0P).  I fixed problem 1 with a new diagnostic in
UNKNOWN in the initial 3.0P release.  I addressed problem 2 with a new
warning in the main programs.

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

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