Published by Jürg Ott, Columbia University, New York
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.
Second Annual meeting of the INTERNATIONAL GENETIC EPIDEMI-
OLOGY SOCIETY, October 10-11, 1993 - New Orleans, Louisiana.
The meeting will be held in the Monteleone Hotel (French
Quarter) and will begin on Sunday, Oct. 10th with a joint
symposium with the American Society of Human Genetics on
"Genetic & Environmental Aspects of Disease." For further
information and abstract forms please contact Louisiana State
University Medical Center Foundation, Division of Professional
Education, 433 Bolivar Street, New Orleans, LA 70112 - Phone
#(504) 568-3712/FAX #(504) 568-3460.
The ftp site presently works fine as far as we can tell. However, because of local network congestion in the afternoon, please access the site during off-peak hours as transfer may be impossible during periods of heavy network activity. To access our site, use the command
ftp york.ccc.columbia.edu or ftp 128.59.97.32
When asked for a login name, enter ANONYMOUS. A password is not
required. For reports on problems please send e-mail to
joe@york.ccc.columbia.edu (Joe Terwilliger).
The host computer, YORK.CCC.COLUMBIA.EDU, is running Desktop-
VMS Version 1.2, so the directory syntax must be specified in VMS
format, which is different from UNIX-based ftp sites. When you
reach our computer, you will be in directory [anonymous], which is
the root directory for the ftp site. All higher directories are
off-limits, and any attempt to access such directories will block
any further activity for you. That root directory contains a file,
README.TXT, which contains a description of the directory structure
and a list of all files available from the ftp site.
Each of the subdirectories in the ftp site contains a file with the directory name and extension .TXT. This file briefly describes the contents of the subdirectory. As an example, the directory [anonymous.pub.newsletter] contains the current and past issues of the Linkage Newsletter. Eventually, it will contain all newsletters published by us since the first issue of August 1987. Please note: We are still sending out the newsletter by e-mail. If you want to receive it by e-mail as soon as a new issue is ready, send a message to: jurg.ott@columbia.edu
When you logon, you will notice that there are some files in the root directory. These are all account specific files, which are read/write protected. You must go to the subdirectory PUB.DIR, with VMS syntax [anonymous.pub]. You can get there by typing CD [.pub], for example, if your computer is running UNIX ftp software. A directory name preceded by a "." means a subdirectory. If the "." is not given, the computer will think you are trying to access a higher-level directory, and will block further access to the system. If, for example, you are in the directory [anony- mous.pub.linkage.dos], and you want to move to the directory [anonymous.pub.linkage], you could enter CD [-], where the "-" sign means to go back one directory level. To move to the directory [anonymous.pub.tlinkage.dos], you could enter CD [--.tlinkage.dos], meaning back up two levels, and then move forward to subdirectory [.tlinkage.dos]. If you have any further questions about VMS directory syntax, or are having difficulty navigating around the ftp site, please send e-mail to Joseph Terwilliger (JOE@YORK.CCC.COLUMBIA.EDU).
To get any files other than ASCII files (*.EXE or *.W51 files, for example, are non-ASCII), please make sure you do this in binary mode. Typically, one should type SET TYPE BINARY at the ftp prompt, though the exact syntax may vary from system to system. If you further must use communications software like KERMIT to get the binary files from a UNIX or VMS machine to your PC, be sure to do those transfers in BINARY format as well.
The OS/2 version of LINKAGE version 5.2 is in preparation and should be available in August. It is being adapted to NDP Pascal for OS/2, which is just now becoming available from Microway, Inc. (tel. (508 746 7341, fax (508) 746 4678). The previous, pre- release version already had excellent qualitites (see Linkage Newsletter of February 1993).
1) The program constant, fitmodel, must be set to true and the program recompiled.
2) Whenever all individuals in a pedigree are untyped for a marker, the UNKNOWN program makes those individuals homozygous for the 1 allele at that marker. While this speeds up calculations considerably, it leads to wrong results in the estimation of allele and haplotype frequencies. A possible solution is simply not to use the UNKNOWN program. We have slightly amended the UNKNOWN program such that it contains a program constant, makehomozygous, which should be set to false if no unknown phenotypes should be turned into homozygotes 1 1. A compiled version of UNKNOWN with makehomozygous set to false is furnished in executable form as UNKNOWN1.EXE.
The input file to the URP program has a format similar to the one used in the LIPED program. However, genotypes can only be coded with alphabet letters, so there are up to 52 different allele codes as upper and lower case letters distinguishable. Besides, the URP program only recodes one marker at a time. Since genotypes in input files to the LINKAGE programs are coded with numbers, one must replace these numbers by letters. As the URP program only recodes one marker at a time, repeatedly modifying the input file for URP is inevitable. If one wants to use the output file resulting from URP as input to a linkage program other than LIPED, one must change the letters back to numbers. Since the whole procedure is very time consuming, we only tested the program with two-point analysis.
We used nine families in the pedigree file, each family with approximately 14 individuals. There were two markers with 12 and 9 alleles, respectively. All but seven individuals were untyped. We ran MLINK (PC version) and LIPED based on the original dataset, and then reduced the number of alleles by running the URP program, which reduced the number of alleles in the first marker from 12 to 4, and in the second one from 9 to 3. We assigned equal allele frequencies to the recoded makers and then ran MLINK and LIPED again. The results turned out to be identical. The elapsed time for the recoded dataset was much shorter than for the original data set, for example, 3 seconds versus 125 seconds. Note, however, that not knowing the allele frequencies can create problems for the analysis (J. Ott, Am J Hum Genet 51:283-290, 1992).
DISCLAIMER: The above investigation was carried out because we keep receiving requests regarding the availability of such programs. We do not endorse the URP program in any way. Its application may be problematic in several respects that we are not pursuing any further. For example, with untyped individuals present in a pedigree, exact solutions become extremely cumbersome (Ott [1979] Cytogenet Cell Genet 25:196). Also, the algorithm applied in the URP program focuses on twopoint analysis, but cases are known in which pairwise comparisons are uninformative yet the multipoint analysis is not. The most urgent need for downcoding alleles is in multipoint analysis, but it is not clear whether the procedure employed in URP consistently works fine for multipoint analysis. For the time being, we choose to carry out downcoding by hand even though it may be tedious.