Linkage Newsletter

Jurg Ott OTT at NYSPI.bitnet
Thu Jul 9 21:04:19 EST 1992

                       Linkage Newsletter
                  Vol. 6   No. 2   July 1992

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

Postal address:  Columbia University, Unit 58
        722 West 168th Street, New York, NY 10032


        This summer issue of the newsletter is rather short.  It is
again being distributed via e-mail (to the GENETIC-LINKAGE news-
group of the BIOSCI network and to individual subscribers) as
well as by postal mail.  Hope everyone has a nice summer!


        The following linkage courses are scheduled:

        Zurich (Advanced course):  October 19-23, 1992, in the
Computer Center at the University of Zrich, Irchel campus.

        New York (Advanced course):  January 11-15, 1993, in the
microcomputer classroom of the Health Sciences library, Columbia
University (supported by National Center for Human Genome Re-
search;  only a small number of participants from outside the
U.S. can be admitted).  Registration is open; topics covered are
as in the Zrich course.  A formal course announcement will be
made later.

        In the spring of 1993, there will also be introductory
courses in New York and Zrich but dates have not yet been fixed.
For information and application forms for any course, please
write (preferably by fax) to Katherine Montague, course coordina-
tor, at the address given above.


        Bug in Vax version of MLINK?

        Joseph Terwilliger recently noticed the following discrepan-
cy between the Vax version and the PC version of the MLINK
program.  Consider two parents and their child who are typed for
two 2-allelic markers.  Both parents are heterozygous, 1/2, at
each locus and the child is homozygous, 1/1, at each locus.
There is complete linkage disequilibrium, P(1-1) = P(2-2) = 0.5,
and P(1-2) = P(2-1) = 0.  Without allelic association, of course,
this family is uninformative for linkage.  Under complete dis-
equilibrium, however, given the offspring's phenotype, parental
phases are known and lead to two nonrecombinations.  Thus, the
lod score is given by Z(t) = log[4(1-t)^2], which has a maximum of
0.60 at t=0.  This is also the result furnished by the PC version
of MLINK, but the Vax version reports zero lod scores at any t.
We are investigating this matter and will report results as soon
as possible.

        Undeclared loops

        In the LINKAGE programs, when loops (marriage or consanguin-
ity loops) are present in a pedigree, this must be specified in the
pedigree file (the safest method is to use the MAKEPED program).
If a loop remains undeclared, depending on the type of loop, the
analysis programs may terminate with an error or, worse, they may
appear to terminate normally but give incorrect results.  Xiaoli
Xie has now written a program to detect loops (Xie X, Ott J
[1992] Am J Hum Genet, abstr, in press).  It is best run after
MAKEPED in which case it catches any loops the user failed to
declare.  This LOOP program is based on the depth-first search
algorithm in graph theory and is freely available.

        Simulating under heterogeneity in SLINK

        Both the SIMLINK (M. Boehnke) and SLINK (D. Weeks) programs
allow for simulating pedigree data under heterogeneity, that is,
with a given proportion of families simulated without linkage
between trait locus and marker loci.  In the analysis, however,
there is a major difference between the two programs:  The SIM-
LINK program analyses the data under heterogeneity while the
analysis programs of the SLINK package do not.  Some users have
previously been unaware of this and have analyzed the data under
homogeneity even though they had been generated by SLINK under
heterogeneity (the resulting expected lod scores are too small).
The program ELODHET was developed to allow analysis under hetero-
geneity for data generated by the SLINK program.  It is part of
the current package of SLINK.

        Change in the LINKLODS program

        The LINKLODS program, which comes with the PC version of
LINKAGE, calculates lod scores for individual families from the
output of MLINK or LINKMAP.  Dr. Chantal Mrette recently pointed
out that occasionally the LINKLODS program gives incorrect
"total" lod scores.  This occurred when a large number of fami-
lies was analyzed and the total log likelihood was smaller than
the program constant lowlod, which previously was set to -500.
This constant has now been changed to a value -10000 so that the
error should no longer occur.  The current program version is
1.70 (6 July 1992).

        Linkage analysis with highly polymorphic markers

        Large numbers of alleles can pose problems in linkage
analysis.  Various exact and approximate ways of overcoming these
problems have been proposed.  Before discussing an overview of
these possibilities, I would like to ask the readers if anyone
has experience with the URP program (Michael S. Braverman: "An
algorithm to improve the computational efficiency of genetic
linkage analysis," Comp Biomed Res 18, 24-36, 1985).  Please let
me know D I'm sure many researchers will be interested in this

(Support through grant HG00008 is gratefully acknowledged)

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