From owner-gene-linkage@net.bio.net Tue Aug 01 23:00:00 1995 Path: biosci!bcm!news.msfc.nasa.gov!newsfeed.internetmci.com!tank.news.pipex.net!pipex!news.sprintlink.net!uunet!in2.uu.net!newsflash.concordia.ca!canopus.cc.umanitoba.ca!news From: Tracey Weiler Newsgroups: bionet.molbio.gene-linkage Subject: Re: Linkage Courses Date: 2 Aug 1995 19:05:18 GMT Organization: University of Manitoba Lines: 18 Message-ID: <3voi9e$p4f@canopus.cc.umanitoba.ca> References: NNTP-Posting-Host: wroge3.biochem.umanitoba.ca Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 1.2b4 (Windows; I; 16bit) This is the www address of the linkage group at Columbia. It has a list of the courses that are being offered - When and where. http://linkage.cpmc.columbia.edu:80/./ There is also a site with a lot of linkage stuff on it that might also be of use to you at: http://lenti.med.umn.edu/linkage/linkage.html ----------------------------------------------------- Tracey Weiler Department of Biochemistry and Molecular Biology University of Manitoba 770 Bannatyne Ave. Winnipeg, MB R3J 3S6 (204) 789 - 3231 FAX: (204) 783 - 0864 ---------------------------------------------------- From owner-gene-linkage@net.bio.net Wed Aug 02 23:00:00 1995 Path: biosci!bcm!cs.utexas.edu!news.sprintlink.net!gatech!usenet.eel.ufl.edu!news.gmi.edu!msunews!harbinger.cc.monash.edu.au!bunyip.cc.uq.oz.au!news From: "Albert Ng T.H." Newsgroups: bionet.molbio.gene-linkage Subject: Biotechnology company positions Date: 3 Aug 1995 06:23:37 GMT Organization: ForBio Research Australia Pty Ltd Lines: 86 Message-ID: <3vpq19$j4p@dingo.cc.uq.oz.au> NNTP-Posting-Host: eucalypt.client.uq.edu.au Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 1.1N (X11; I; SunOS 5.4 sun4m) X-URL: news:bionet.molbio.gene-linkage ForBio Research is a key part of the ForBio group of companies based in Brisbane which now has branches in Europe, Malaysia and China, with operations planned to commence in the USA within 12 months. The Australian operations currently employ over 50 staff, and it is planned that the international group will expand to 250 personnel within three years. ForBio Research Pty Ltd is the largest private Australian plant biotechnology group, and the largest forest biotechnology research company worldwide. It has a staff of over 30 which will expand to about 40. The company has an overriding commitment to excellence, and operates in well-equipped laboratories in Brisbane, with linkages to the University of Queensland. Applications are sought from outstanding PhD level scientists to strengthen our gene transformation and marker-aided selection programs. Talented Research Assistants are also being appointed in each of these areas as well as to our molecular biology programs. RESEARCH SCIENTISTS (MOLECULAR BREEDING) Quantitative Geneticist or Breeder with a PhD qualification and experience in use of molecular markers is sought for a senior role in our mapping team, developing correlations between quantitative trait loci and map markers using advanced software packages. This group is one of the most productive in the world and expects to generate over a million RAPD reactions per year using automated methods. Ability to manage a dynamic team and to interact with other professionals both within and external to the ForBio group is desirable. The group is also developing capabilities in positional cloning and there is potential for appointees to have direct or indirect participation in this program. RESEARCH SCIENTIST (PLANT TRANSFORMATION) Our transformation team is involved in development of robust transformation systems for an increasing variety of woody plants. Both Agrobacterium and particle bombardment systems are currently used by the group. It is expected that the team will be involved in the development of methods for robot-assisted subculture in association with ForBio Robotics. Interest in the longer-term goal of developing targeted gene insertion methods would be well regarded. A PhD qualified scientist is sought who has relevant technical skills and who will also be able to provide team coordination and communication in areas of responsibility. TECHNICAL SERVICES OFFICER (SCIENTIFIC EQUIPMENT SPECIALIST) An experienced and talented equipment specialist is sought who can provide hands-on maintenance, service and modification of advanced biotechnological equipment worth over a million dollars. A variety of background experience could suit this role, including electronics or operational experience with laboratory equipment, but a strong interest in the operation of computer-controlled biotechnology equipment is essential. The appointee will be broadly responsible for the physical maintenance of equipment (with appropriate outside services), and for assisting in development of new applications. PROGRAM COORDINATOR /COMMUNICATOR A biotechnologist with good writing and communication skills is sought to assist scientists in an active research group, particularly the CEO, with project scoping, reporting and general communication. It is likely that the successful applicant will have a PhD and experience in plant biotechnology or a related field of research, but now wishes to pursue a -- career in a non-laboratory role. Other skills, such as in documentation of intellectual property, will be well regarded. RESEARCH ASSISTANTS (MOLECULAR BIOLOGY) Graduates, preferably with BSc(Hons) or MSc qualifications, are required to assist molecular biology research studies involving isolation and characterisation of genes, preparation of gene constructs, sequencing, mapping with molecular markers, and related studies. Laboratory research experience will be well regarded, but is not essential for individuals who are eager to learn. ForBio Research has a philosophy of supporting individual creativity to address agreed team goals in a cooperative and harmonious environment. Attractive remuneration packages commensurate with the responsibilities of the respective positions will be negotiated with successful candidates. Applications including a detailed curriculum vitae and the names of three referees should be forwarded by 13 August 1995 to ForBio Research Pty Ltd, 50 Meiers Road, Indooroopilly, Qld, 4068, Email:S.Hedley@forbio.com.au. Further information can be obtained from Ms Edith Mendelle or Professor Bob Teasdale on +61-7-870 5888, fax: +61-7-870 5777 or email: S.Hedley@forbio.com.au. ________________________________________________________________ Albert Ng T.H. (Computer Scientist) ForBio Research Australia - "Working towards a Greener World" email: albert@forbio.com.au mobile: 015 65 4681 phone: +61 7 870 5888 fax: +61 7 870 5777 ________________________________________________________________ From owner-gene-linkage@net.bio.net Wed Aug 02 23:00:00 1995 Path: biosci!bcm!cs.utexas.edu!news.sprintlink.net!EU.net!uunet!in1.uu.net!spcuna!news.columbia.edu!konichiwa.cc.columbia.edu!jo7 From: Jurg Ott Newsgroups: bionet.molbio.gene-linkage Subject: Re: Linkage Courses Date: Thu, 3 Aug 1995 06:16:21 -0400 Organization: Columbia University Lines: 14 Message-ID: References: NNTP-Posting-Host: konichiwa.cc.columbia.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII X-Sender: jo7@konichiwa.cc.columbia.edu In-Reply-To: On 28 Jul 1995, Kevin Clancy PhD wrote: > Dear All, > > Does anyone know when Jurg Ott's Linkage courses start up? > Info on how to apply would also be most welcome. Look in our anonymous ftp site, linkage.cpmc.columbia.edu, in directory 'info' - the 'courses.txt' file provides dates. Or consult our WWW home page (see below). Jurg Ott Email: jurg.ott@columbia.edu WWW: http://linkage.cpmc.columbia.edu From owner-gene-linkage@net.bio.net Thu Aug 03 23:00:00 1995 Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!newsfeed.internetmci.com!news.sprintlink.net!uunet!in1.uu.net!noc.near.net!das-news2.harvard.edu!oitnews.harvard.edu!news.sesqui.net!rice!cs.rice.edu!schaffer From: schaffer@cs.rice.edu (Alex Schaffer) Newsgroups: bionet.software,bionet.molbio.gene-linkage Subject: FASTLINK 2.3P available, runs in parallel Date: 4 Aug 1995 14:37:11 GMT Organization: Rice University Lines: 166 Message-ID: <3vtban$aob@larry.rice.edu> NNTP-Posting-Host: cs.rice.edu Xref: biosci bionet.software:12926 bionet.molbio.gene-linkage:796 The purpose of this note is to announce the availability of FASTLINK 2.3P. FASTLINK is a faster version of the principal linkage analysis programs in LINKAGE 5.1. Thanks to Lucien Bachner, Carolyn Bucholtz, John Powell, Gyorgy Simon, Jim Tomlin, and Garret Taylor for assistance with beta testing and portability testing of the parallel code. Thanks to Margaret Gelder Ehm, Carol Haynes, Patricia Kramer, Toby Nygaard, Marcy Speer, Gerard Tromp, Frank Visser for bug reports and suggestions that helped in developing version 2.3P. Thanks to Anita Destefano and Kimmo Kallio for assistance with portability to VMS. As with previous versions, FASTLINK 2.3P can be ftp-ed from softlib.cs.rice.edu in the directory pub/fastlink The main advance over FASTLINK 2.2 is that much of the code can now run in parallel, which explains the P in the new version. Most of this message will focus on the parallel code, but let me put some remarks about the sequential code first, so that those who want only sequential code can skip the rest. |*| Sequential Code --------------- Version 2.3P has some improvements in the sequential code and documentation, which are covered at the end of README.updates. New features include speeding up runs involving multiple LINKMAP scripts that move a marker across a fixed map. The organization of the code files and Makefile has changed substantially, so that the same files can be used to make both sequential and parallel executable files. There is a new auxiliary program called ofm ("optimize for maxhap") to assist with automatic recompilation of the programs. |*| Parallel Code, Introduction --------------------------- The (sequential) FASTLINK package already provides considerable running time improvements over the older programs for the LINKAGE package. Response from users about sequential FASTLINK has been extremely enthusiastic and yet, it is abundantly clear that more speedup is necessary. At this time, we believe that one realistic way to obtain substantially more speedup on long runs is to use multiple processors in parallel. We continue to investigate further sequential speedups. Two attempts to parallelize ILINK from FASTLINK are described in the papers: 3. Sandhya Dwarkadas, Alejandro A. Schaffer, Robert W. Cottingham Jr., Alan L. Cox, Peter Keleher, and Willy Zwaenepoel, Parallelization of General Linkage Analysis Problems, Human Heredity 44(1994), pp. 127--141. 4. Sandeep K. Gupta, Alejandro A. Schaffer, Alan L. Cox, Sandhya Dwarkadas, and Willy Zwaenepoel, Integrating Parallelization Strategies for Linkage Analysis, Computers and Biomedical Research 28(1995), pp. 116-139. These two papers are available as paper3.ps and paper4.ps with the distribution. The version of parallel ILINK that we are distributing is similar algorithmically to that described in the second paper. We were able to achieve speedups in the 5 to 7 range on a network of 8 DECStation5000/Ultrix processors on ILINK runs that take tens of minutes sequentially. |*| Parallel FASTLINK, Operation ---------------------------- FASTLINK 2.3P can be run in parallel on two different types of platforms: shared-memory multiprocessors and networks of UNIX workstations. FASTLINK on shared-memory multiprocessors: The shared-memory version uses the p4 macros which are available by anonymous ftp to Argonne National Labs. More detailed retrieval and installation instructions can be found in README.p4 that comes with FASTLINK. FASTLINK on network of workstations: If you have access to a network of (uniprocessor) Unix workstations, then you can run parallel FASTLINK using a runtime package called TreadMarks. TreadMarks essentially provides the same execution environment on a network of workstations as that available on shared-memory multiprocessors. TreadMarks is available for a small fee for universities and medical schools, and at commercial rates for other institutions. All users can get a 30-day free trial license. See README.TreadMarks for more details on how to configure FASTLINK with TreadMarks. TreadMarks licenses can be obtained by sending e-mail to treadmarks@ece.rice.edu. Please specify the nature of your organization (commercial or university/medical school) and the machine architecture and operating system you plan to use TreadMarks for. Once you return the signed license and the license fee, a copy of TreadMarks will be sent to you or be made available via ftp. A free 30-day demo copy can also be obtained by sending e-mail to the same address. We recognize that installing the parallel code is more difficult that installing the sequential code because of the need to configure both the FASTLINK code and the runtime library (either p4 or TreadMarks). We will be pleased to work with you in getting the parallel code up and running on your system. |*| Parallel FASTLINK, References The main references for sequential FASTLINK are: 1. R. W. Cottingham Jr., R. M. Idury, and A. A. Schaffer, Faster Sequential Genetic Linkage Computations, American Journal of Human Genetics, 53(1993), pp. 252-263. 2. A. A. Schaffer, S. K. Gupta, K. Shriram, and R. W. Cottingham, Jr., Avoiding Recomputation in Genetic Linkage Analysis, Human Heredity, 44(1994), pp. 225-237. 5. G. M. Lathrop, J.-M. Lalouel, C. Julier, and J. Ott, Strategies for Multilocus Analysis in Humans, PNAS 81(1984), pp. 3443-3446. 6. G. M. Lathrop and J.-M. Lalouel, Easy Calculations of LOD Scores and Genetic Risks on Small Computers, American Journal of Human Genetics, 36(1984), pp. 460-465. 7. G. M. Lathrop, J.-M. Lalouel, and R. L. White, Construction of Human Genetic Linkage Maps: Likelihood Calculations for Multilocus Analysis, Genetic Epidemiology 3(1986), pp. 39-52. One reference for p4 is: 8. R. Butler and E. Lusk. Monitors, Messages and Clusters: The p4 Parallel Programming System, Parallel Computing 20(1994), pp. 547-564. One reference for TreadMarks is: 9. P. Keleher, A.L. Cox, S.Dwarkadas, and W. Zwaenepoel, TreadMarks: Distributed Shared Memory on Standard Workstations and Operating Systems, Proceedings of the Winter 94 Usenix Conference, pp. 115-131, January 1994. FASTLINK 2.3P represents the conjunction of 5 substantial research efforts and software engineering projects. Therefore, if you use FASTLINK in parallel, we ask that you cite: at least one of 5,6,7 to give credit to LINKAGE at least one of 1,2 to give credit to sequential FASTLINK at least one of 3,4 to give credit for the parallel algorithms and either 8 (p4) or 9 (TreadMarks) to give credit for the runtime library that you use. Sincerely, Chris Hyams and Alejandro Schaffer and Alan Cox and Sandhya Dwarkadas and Willy Zwaenepoel Rice University cgh@cs.rice.edu schaffer@cs.rice.edu alc@cs.rice.edu sandhya@cs.rice.edu willy@cs.rice.edu From owner-gene-linkage@net.bio.net Thu Aug 03 23:00:00 1995 Path: biosci!DOLPHIN.UPENN.EDU!stein From: stein@DOLPHIN.UPENN.EDU Newsgroups: bionet.molbio.gene-linkage Subject: postdoc position-wanted Date: 3 Aug 1995 17:28:52 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 47 Sender: daemon@net.bio.net Distribution: world Message-ID: <199508040026.UAA25819@dolphin.upenn.edu> NNTP-Posting-Host: net.bio.net From MAILER-DAEMON@noc4.dccs.upenn.edu Thu Aug 3 20:21:50 1995 Received: from noc4.dccs.upenn.edu by dolphin.upenn.edu id UAA27424; Thu, 3 Aug 1995 20:21:50 -0400 Posted-Date: Thu, 3 Aug 1995 20:21:50 -0400 Received-Date: Thu, 3 Aug 1995 20:21:50 -0400 Received: from DOLPHIN.UPENN.EDU by noc4.dccs.upenn.edu id AA03338; Thu, 3 Aug 95 20:21:47 -0400 Date: Thu, 3 Aug 95 20:21:47 -0400 From: MAILER-DAEMON@noc4.dccs.upenn.edu (Mail Delivery Subsystem) Subject: Returned mail: Host unknown Message-Id: <9508040021.AA03338@noc4.dccs.upenn.edu> To: Status: RO ----- Transcript of session follows ----- 550 ... Host unknown ----- Unsent message follows ----- Received-Date: Thu, 3 Aug 95 20:21:47 -0400 Return-Path: Received: by dolphin.upenn.edu id UAA27347; Thu, 3 Aug 1995 20:21:46 -0400 Posted-Date: Thu, 3 Aug 1995 20:21:46 -0400 Message-Id: <199508040021.UAA27347@dolphin.upenn.edu> Subject: To: stein@dolpin.upenn.edu Date: Thu, 3 Aug 1995 20:21:46 -0400 (EDT) *** PLEASE, DON'T RESPONSE BY 'REPLY' COMMAND *** SUBJECT: Seeking for postdoctoral position in US FIELD: Molecular Biology & Genetics of Oncogenes or Antioncogenes SKILLS: Cloning, sequencing, mutagenesis, PCR (RT-PCR), Southern & Northern blotting, immunoprecipitation, CAT, tissue culture, tumor induction, PC, publications registered in CC, etc. WHEN: available immediately, further information upon request ADDRESS: stein@dolphin.upenn.edu From owner-gene-linkage@net.bio.net Sun Aug 06 23:00:00 1995 Path: biosci!bcm!news.msfc.nasa.gov!newsfeed.internetmci.com!news.sprintlink.net!news.clark.net!voland From: voland@clark.net (Voland) Newsgroups: bionet.molbio.gene-linkage Subject: Anyone believing that homosexuality Date: 7 Aug 1995 21:04:09 GMT Organization: Clark Internet Services, Inc., Ellicott City, MD USA Lines: 14 Message-ID: <405v49$fkq@clarknet.clark.net> NNTP-Posting-Host: clark.net Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=ISO-8859-1 Content-Transfer-Encoding: 8bit X-Newsreader: TIN [version 1.2 PL2] Hello. My name is Stan L. Liberman and I am conducting the research on the causes of homosexuality. Please help me if you have a different opinions about that, and you believe that 1.) homosexuality exist/does not exist in animals 2.) homosexuality is a genetic/mental/neurological disorder 3.) homosexuality is natural/unnatural And have the reference to support it Please e-mail me to voland@clark.net to Stan L. Liberman From owner-gene-linkage@net.bio.net Tue Aug 08 23:00:00 1995 Path: biosci!ns1.faseb.org!darwin.sura.net!mother.usf.edu!news From: tabibzadeh@rics.moffitt.usf.edu (SIAMAK TABIBZADEH) Newsgroups: bionet.molbio.gene-linkage Subject: Frontiers in Bioscience, an electronic journal and virtual library Date: 9 Aug 1995 16:35:14 GMT Organization: Moffitt Cancer Center at USF Lines: 40 Message-ID: <40ao42$rp6@mother.usf.edu> NNTP-Posting-Host: pc3160.moffitt.usf.edu Mime-Version: 1.0 X-Newsreader: WinVN 0.93.11 Frontiers in Bioscience, an electronic journal and virtual library An electronic journal and virtual library has been created in order to facilitate rapid dissemination of scientific data as well as to provide investigators with numerous online tools for use in their day-to-day research activities. The publication cost is minimized or completely eliminated. A section of the journal is dedicated to publishing manuscripts that contain real time events. Access to a large number of databases is quite easy from the journal. These include databases for analysis of scientific data, search strategies, dictionaries, atlases, tutorials, conferences, information on products of various manufacturers, links to online journals and many other valuable information. Access to the journal and these services is free. The staff members of the journal are in the process of creation of various databases. One such database on gene knockout is already online. The journal can be accessed at the following address on WWW: http://bayanet.com/bioscinece Although submission of data for publication in electronic platforms has just begun, this method of distribution of scientific information would certainly be the logical route of the future. The first volume of the journal to be published around Jan 1996 will contain excellent manuscripts. Please take a moment to examine the journal and consider to send manuscripts for publication in this new and novel forum. The address of the editorial office is as follows: Frontiers in Bioscience S Tabibzadeh, MD, Dept of Pathology University of South Florida 12901 Bruce B Downs Blvd Tampa, FL 33612 Tel: 813-979-7237 Fax: 813-979-3085 E-mail: tabibzadeh@rics.moffitt.usf.edu From owner-gene-linkage@net.bio.net Tue Aug 08 23:00:00 1995 Path: biosci!daresbury!not-for-mail From: h7336kal@ella.hu Newsgroups: bionet.molbio.gene-linkage Subject: linkage map of pea Date: 9 Aug 1995 15:06:01 +0100 Lines: 12 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <40afc9$o4s@mserv1.dl.ac.uk> Discarded-X400-IPMS-Extensions: ccitt (0) data (9) pss (2342) (2342) (19200300) (200) (1) Original-To: gen-link@dl.ac.uk Dear Netters, Can anybody help me to get a relative new version of linkage map of Pisum sativum exception Ellis et al. (1992) Genetics 130:649-663? Thanks a lot, Peter Kalo Biological Research Center of Hungarian Academy of Sciences Institute of Genetics P.O. Box 521 H-6701 kal7336@helka.iif.hu From owner-gene-linkage@net.bio.net Tue Aug 08 23:00:00 1995 Newsgroups: bionet.molbio.gene-linkage Path: biosci!daresbury!nntp-trd.UNINETT.no!Norway.EU.net!EU.net!howland.reston.ans.net!vixen.cso.uiuc.edu!sdd.hp.com!caen!zip.eecs.umich.edu!umn.edu!lenti.med.umn.edu!dean From: dean@lenti.med.umn.edu (Dean Flanders) Subject: BIONET.MOLBIO.GENE-LINKAGE.FAQ Message-ID: Sender: news@news.cis.umn.edu (Usenet News Administration) Nntp-Posting-Host: lenti.med.umn.edu Organization: University of Minnesota, Twin Cities X-Newsreader: TIN [version 1.2 PL2] Date: Wed, 9 Aug 1995 05:06:57 GMT Lines: 886 BIONET.MOLBIO.GENE-LINKAGE FREQUENTLY ASKED QUESTIONS (FAQ) AS OF 1995/06/09 1.0) FAQ ADMINISTRATIVE INFORMATION [1995/05/18] 1.1) Where can I obtain and/or access the bionet.molbio.gene- linkage FAQ? [1995/03/01] 1.2) Who created the bionet.molbio.gene-linkage FAQ? [1995/03/01] 1.3) How can I help improve this FAQ? [1995/03/01] 1.4) Contributors to this FAQ. [1995/06/09] 1.5) When was the FAQ last updated? [1995/06/09] 2.0) INFORMATION RESOURCES 2.1) What anonymous FTP sites have programs/utilities useful for linkage analysis? [1995/03/01] 2.2) What books are helpful when learning about linkage analysis? [1995/03/01] 2.3) What WWW sites have useful linkage information? [1995/06/02] 2.4) What gopher sites have useful linkage information? [1995/03/01] 2.5) What "linkage centers" make information and assistance available to researchers? [1995/05/31] 2.6) What journals are useful for linkage analysis? [1995/06/02] 2.7) What courses are offered in linkage analysis? [1995/06/02] 3.0) GENE-LINKAGE SOFTWARE OVERVIEW 3.1) What database management programs do people use for linkage data? [1995/05/31] 3.2) What programs are available for pedigree drawing? [1995/04/01] 3.3) What linkage analysis helper programs are available? [1995/04/01] 3.4) Why are some programs used primarily for chromosome mapping, while others are used for disease mapping? [1995/03/01] 3.5) What programs are used for chromosome mapping? [1995/05/31] 3.6) What programs are used for disease gene mapping? [1995/04/01] 3.7) What programs are available for running genetic simulations? [1995/03/01] 3.8) What programs are available to help detect errors in linkage data? [1995/03/01] 3.9) What programs help me recode genetic markers? [1995/03/01] 4.0) LINKAGE PACKAGE SPECIFIC INFORMATION 4.1) How do I get my CEPH data into CRI-MAP format? [1995/03/01] 4.2) How do you calculate MAXHAP? [1995/03/01] 4.3) When should you use binary coding instead of numeric allele coding? [1995/03/01] 4.4) What do you do when allele frequencies do not add up to 1; for example, when alleles are not present in a pedigree under study? [1995/03/01] 4.5) I use LINKAGE and/or FASTLINK. Which references should I include in my papers? [1995/03/01] 4.6) What is recoding of alleles all about anyway? [1995/03/01] 5.0) COMPUTER ADMINISTRATION AND OPTIMIZATION 5.1) How w can I increase the speed of the LINKAGE/FASTLINK package on my workstation? [1995/05/18] 1.0) FAQ ADMINISTRATIVE INFORMATION 1.1) Where can I obtain the bionet.gene-linkage FAQ? [1995/03/01] It is available by anonymous FTP from lenti.med.umn.edu in /pub/linkage. The best way to view the FAQ is via the WWW, from http://lenti.med.umn.edu/linkage/linkage.html. The FAQ is also available via gopher at lenti.med.umn.edu in /Biologically Related Information/Linkage Analysis. The FAQ will also be posted in the USENET groups bionet.molbio.gene-linkage and news.answers the 1st and 15th of each month. 1.2) Who created the bionet.molbio.gene-linkage FAQ? [1995/03/01] Darrell Root (rootd@ohsu.edu) originally started the bionet.molbio.gene-linkage FAQ in May of 1994 in an attempt to share information and experiences that may be of use to other people involved in linkage analysis. I am Dean Flanders (dean@lenti.med.umn.edu), the current maintainer of the FAQ, and began my tenure in December of 1994. The FAQ will never serve as a short course in linkage analysis, but instead it will ideally be a place to help beginners get started in the area and to help experts not make the same mistakes as others. All of the information in this FAQ by no means comes completely from Darrell or me, but from a large number of people that work in the area of linkage analysis. Their names are listed at the end of this section of the FAQ. 1.3) How can I help improve this FAQ? [1995/03/01] Feel free to send any information that you think would be beneficial for other people who are just beginning in linkage or have been doing linkage for years to linkage@lenti.med.umn.edu. Also, if there is information you would like to see or errors in this FAQ please let us know by sending email to linkage@lenti.med.umn.edu. If you would like to see something changed or added to the FAQ please to send it in a format that can be quickly incorporated into the FAQ, such as correcting the errors in the section of the FAQ and emailing it back to the FAQ maintainer. 1.4) Contributors to this FAQ. [1995/06/09] David Adler, John Attwood, Michael Boehnke, Marcia Brott, Don Bowden, Michael Braverman, Young B Choi, Kevin Crawford, Dave Curtis, Peter Doris, Bennett Dyke, David Featherstone, Dean Flanders, Jonathan Haines, Rob Harper, Pierre Janssens, David Kikuchi, Wentian Li, Tim Little, Tara Matise, Eli Meir, Mike Miller, Jurg Ott, Darrell Root, Alex Schaffer, Robert Stodola, Frank Visser, Dan Weeks, Ellen Wijsman, Scott Wildenberg, Matthias Wjst, and Kim Worley. 1.5) When was the FAQ last updated? [1995/06/09] The last update of the FAQ was on 1995/06/09. All sections should indicate what month and year they were last updated. 2.0) INFORMATION RESOURCES 2.1) What anonymous-FTP sites have programs/utilities useful for linkage analysis? [1995/03/01] At present there is no one site that serves as a repository for all linkage software. So the best way of finding FTP site information is to read the software package information below, which should provide all of the necessary FTP information. 2.2) What books are helpful when learning about linkage analysis? [1995/03/01] Bishop, M. J. “Guide to Human Genome Computing.” Academic Press, 1994. Davies, K. E. "Human Genetic Diseases - A Practical Approach." IRL Press, Oxford England and Washington, D.C., 1986. Dracopoli, N. C., Haines, J. L., Korf, B. R., Moir, D.T., Morton, C. C., Seidman, C. E., Seidman, J. G., Smith, D. R. “Current Protocols in Human Genetics.” John Wiley and Sons, Inc., USA, 1994. Khoury, M. J., Beaty, T. H., and Cohen, B. H. “Fundamentals of Genetic Epidemiology.” Oxford University Press, 1993. Ott, J. “Analysis of Human Genetic Linkage.” Johns Hopkins University Press, 1991. Terwilliger, J. D. and Ott, J. “Handbook of Human Genetic Linkage,” Johns Hopkins University Press, 1994. Thompson, E. A. “Pedigree Analysis in Human Genetics.” Johns Hopkins University Press, Baltimore and London, 1986. 2.3) What WWW sites have useful linkage information? [1995/06/02] This is in no way an attempt to list the explosion of WWW sites of biological interest on the Internet, but it is a listing of some of the major ones and ones of particular interest in linkage analysis. http://www- bprc.mps.ohio-state.edu/cgi-bin/hpp?genetics.html, is a very comprehensive listing of resources available on the Internet in the area of genetics. In particular there are links to many of the genome centers on the Internet. http://lenti.med.umn.edu/linkage/linkage.html, which is serving as linkage analysis home page, will have links to all of the WWW sites listed as well as gopher servers and a hypertext version of the FAQ. http://www.genethon.fr, the Genethon Center, Genethon’s home page. http://www.chlc.org, the Cooperative Human Linkage Center, CHLC’s home page. http://gdbwww.gdb.org has a version of GDB available and access to OMIM. http://www.pathology.washington.edu has human and mouse standard idiograms. The idiograms are useful for making illustrations for gene mapping and for constructing abnormal chromosomes. The PostScript idiograms can be manipulated band by band with illustration software such as Adobe Illustrator, Aldus FreeHand, Canvas, and Altsys Virtuoso. http://diamond.gene.ucl.ac.uk gives access to John Attwood’s software on his FTP server as well as local items and the chromosome 9 home page. Also, it has the latest versions of Dave Curtis’ software. http://linkage.cpmc.columbia.edu has a lot of useful information on linkage analysis; in particular it offers information on software, the course offered by J. Ott, and the Linkage Newsletter. 2.4) What gopher sites have useful linkage information? [1995/03/01] There is one that will be maintained with links to other gophers of interest in linkage analysis, as well as links to other gopher servers of biologically related information. It is at lenti.med.umn.edu, and the path to it is Biologically Related Information/Genetic Linkage Analysis. 2.5) What "linkage centers" make information and assistance available to researchers? [1995/05/31] One such center is the Cooperative Human Linkage Center (CHLC). The goal of this center is to generate a high resolution map of the human genome and rapidly distribute this information to the genome community. They are in the process of identifying more human markers and developing high resolution framework maps. One can obtain information about CHLC from via gopher from gopher.chlc.org , http://www.chlc.org , ftp://ftp.chlc.org , info-server@chlc.org, or help@chclc.org. Among other things, CHLC provides primer selection and linkage analysis via email. Information on those services can be found by sending email to: primer- server@chlc.org and linkage-server@chlc.org. David Featherston (davidf@caos.kun.nl) from the Dutch EMBnet Node is starting a linkage analysis service: software availability, support/advice initially, possibly training, and perhaps consultancy. At present they have MapMaker/EXP 3.0b, MapMaker/QTL 1.1, Lathrop and Lalouel's LINKAGE package, and Schaffer’s FASTLINK package. This means that if users have Genomics Package accounts at the CAOS/CAMM Center, they can use these programs on their fast computers to analyze their data sets. Please contact David Featherston if you are interested in more information about such an account. A major European center is the Human Genome Mapping Project Resource Centre in Hinxton, England. It is funded by the Medical Research Council, and has a broad range of software and databases available, mainly focused on the Human Genome Project. In the area of Linkage analysis it has the following programs available: FASTLINK, CRIMAP, MAP MAPMAKER, HOMOZ, PEDPACK, APM, SIMLINK, FASTMAP, COMDS, DOLINK & QDB, HANDLINK, GAS and Jurg Ott's collection of programs. The aim is to have all major (Unix-based) gene linkage packages available for our users. The Center also gives courses on linkage analysis. More information about the Centre can be obtained from it's home- page: http://www.hgmp.mrc.ac.uk/. If you want to register as user, send e-mail to admin@hgmp.mrc.ac.uk for a registration form. For more information about the gene-linkage services you can contact Frank Visser (fvisser@hgmp.mrc.ac.uk). 2.6) What journals are useful for linkage analysis? [1995/06/02] American Journal of Human Genetics, Annals of Human Genetics, Computer Applications in Biosciences (CABIOS), Genomics, Genetic Epidemiology, Human Genome News (available by gopher from gopher.gdb.org), Human Genome Project Journal, Human Heredity, Journal of Computational Biology, Nature Genetics. 2.7) What courses are offered on linkage analysis? [1995/06/02] There are three primary courses offered throughout the yeart on human linkage analysis. One is a four day course offered once per year by Drs. Margaret Pericak-Vance and Jonathan Haines. The next course will be offered in late April, 1996 in Boston. The focus of the course is on the overall design of a human disease gene mapping study, with particular emphasis on the problems of common/complex disorders. The course covers clinical classification, pedigree ascertainment, collection, and follow-up, basic linkage techniques, linkaghe and association analysis for complex disorders, laboratroy technqiues for genotyping, and gene characterization. The courseemphasizes the global decision-making process, rather than details of specific techniques. For more information write to Genetic Methods Course; c/o Dr. Margaret Pericak- Vance; Division of Neurology, Box 2900; Duke University Medical Center; Durham, NC 27710, or you can send e-mail to genclass@genemap.mc.duke.edu. The remaining two courses are both offered by Jurg Ott on the software used for human linkage. One is a beginner’s course, and the other an advanced course for those familiar with the linkage analysis software. These courses are offered several times throughout the year and you can get more information by contacting Katherine Montague/Jurg Ott; Columbia University, Unit 58; 722 West 168th Street; New York, NY 10032. In addition you can fax to (212)568- 2750 or call (212)960 2507 or email km165@columbia.edu for more information. 3.0) GENE-LINKAGE SOFTWARE OVERVIEW 3.1) What database management programs do people use for linkage data? [1995/05/31] One must be aware that some pedigree drawing software can also serve as databases for data as well as drawing pedigrees, see the next question in the FAQ for a description of those packages. CEPH DBMS: The CEPH DataBase Management System is specifically designed for chromosome mapping with CEPH style pedigrees. It can output data in ped.out format for the LINKAGE package. This program can now be picked up via anonymous FTP from ftp.cephb.fr in pub/ceph_genotype_db. DOLINK: This DOS custom database program by D. Curtis manages genetic data and sets up input files for linkage analysis. It is available from ftp.gene.ucl.ac.uk. The DOS and Windows versions of DOLINK program help manage genetic data and setup analysis. It is available with the C++ source allowing compilation on Unix host running X and possibly a Macintosh. File Express: This is a DOS shareware database which can be used to hold data for DOLINK (largely superseded by QDB). It is available as fe51-a/b/c.zip via FTP from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. LABMAN and LINKMAN: These are linkage analysis databases for holding linkage data and exporting it in various formats for linkage analysis. They are available via anonymous FTP from lenti.med.umn.edu in /pub/linkage/labman. These databases were developed by P. Adams of Columbia University. LYNKSYS: This custom-made database program was written by J. Attwood and S. Bryant. Although they continue to use it, J. Attwood suggests using DOLINK instead. LINKSYS is not currently available at any FTP sites. Map Manager: It is a program for the Macintosh which helps analyze the results of genetic mapping experiments using backcrosses, intercrosses, or recombinant inbred strains. In addition it also has tools for statistical analysis of experiments. The program was created by K. F. Manly at the Roswell Cancer Institute and is available via FTP from mcbio.med.buffalo.edu in /pub/MapMgr. QDB: This is a database program available as DOS and Windows versions and with C++ source allowing compilation for X and possibly Macintosh. It is available as qdb16a.zip via FTP from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. 3.2) What programs are available for pedigree drawing? [1995/04/01] One of the tricks of managing individuals in a mapping study is trying to get the database you are using to export your family data in a format acceptable for input into pedigree drawing programs. The marriage between these two can be of great assistance. However, some pedigree drawing programs have databases as a part of the package. CYRILLIC: This is a pedigree editor for Windows with facilities for including marker data which you can then have it output the input files for LINKAGE. It is Windows-based, so input of the pedigree is very efficient. You also have a data form associated with each individual where you can store names and other pertinent data. It also has the ability to interface with most standard PC databases. This program is not public domain and is available from Cherwell Scientific Publishing. If you would like more information send email to csp@sable.ox.ac.uk and they would be very happy to send you a demo of the program. Version 2 of Cyrillic should be coming out late summer of 1995. FTREE: This is a DOS pedigree program written by R. Go at the University of Alabama. GENETREE: GeneTree 1.0 is a DOS package which provides a convenient way to draw family tree diagrams suitable for genetics or genealogy. The package consists of the GeneTree program, which draws pedigree diagrams using a command language; and SC, using a menu driven program that facilitates creation of GeneTree commands. GeneTree and SC are made available with program manuals, examples of family tree diagrams, and a GeneTree Quick Reference Guide. GeneTree is written in C. Note that it is a DRAWING program and does not compute genetic parameters. The GeneTree program is available from wijsman@max.u.washington.edu at a price of $125 (because of licensing fees from a private company which wrote one of the drivers used in the program). KINDRED: This new DOS database program, distributed by Epicenter Software, is specifically designed for linkage analysis. A free demo is available by calling (818)-304-9487. In addition to database duties, this program will draw pedigrees, haplotype marker data, and can output data in LINKAGE format. PEDPAK: This package is designed to handle large datasets for animals. The package was written and distributed by Alan Thomas, who is in Bath, England. The software is not public domain and must be purchased. PEDDRAW: It is a Macintosh based program, written by B. Dyke, P. Mamelka, and J. MacCleur. It is available from bdyke@darwin.sfbr.org or Pedigree/Draw; Department of Genetics; Southwest Foundation for Biomedical Research; PO. Box 28147; San Antonio, TX 78228-0147. An upgrade from a previous version is $10, the current version is 4.4. Documentation costs $10 printed and the full package including documentation costs $45. There is a script which converts linkage format to PEDDRAW available via anonymous FTP at ftp.ee.pdx.edu in /pub/users/cat/rootd/convert.new. PEDRAW: This program is a pedigree drawing program written by D. Curtis for DOS and available via FTP from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. The most current version is called pedraw16.zip. A companion program to PEDRAW is PEDHELP, it is a pop-up help for PEDRAW. PAP: The Pedigree Analysis Package (PAP) is a set of FORTRAN 77 programs for computing likelihoods and simulating phenotypes of genetic models on pedigrees. It is available via gopher from corona.med.utah.edu in Publicly Accessible Software, probes(sts), etc./software/pap. 3.3) What linkage analysis helper programs are available? [1995/04/01] CEPH2CRI: This program converts to output from the CEPH DBMS into the format useable in CRI- MAP. It can be found at ftp.gene.ucl.ac.uk in /pub/packages/linkage_utils. EASISTAT: This is a DOS statistics package, it contains EASIGRAF which draws graphs of lod scores from the output of FASTMAP. The lod scores first need to be run through the TABLE utility, which is included in the DOLINK and FASTMAP packages. It is available as estat21.zip via anonymous FTP from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. FIRSTORD: A demonstration of a method for preliminary ordering of loci based on two-point lod scores. It is available as DOS executable and C source called first11.zip from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. LINKMED: A program for converting LINKAGE-format files to MENDEL-format files. It is available by anonymous FTP from watson.hgen.pitt.edu as linkmend.tar.Z. MAP: A program to convert LINKMAP output into a table of multipoint lod scores. It is available by anonymous FTP from watson.hgen.pitt.edu as map.tar.Z. PEDREP: A program for converting a MENDEL-format pedigree file ('pedm.dat') to a Pedigree/Draw file for graphical display on a Macintosh. It is available by anonymous FTP from watson.hgen.pitt.edu as pedprep.tar.Z. RECODE: A program for recoding character or sized-allele data into numbered-allele data. It is available by anonymous FTP from watson.hgen.pitt.edu as recode.tar.Z. 3.4) Why are some programs used primarily for human chromosome mapping, while others are used for human disease mapping? [1995/03/01] Any family can be used for chromosome mapping, so CEPH has picked a particular family "shape" and generated a large database with these families. Programs designed for chromosome mapping can be optimized for using these families, reducing the time needed for calculations. Only families afflicted with a disease can be used for disease gene mapping. As a result, programs designed for disease gene mapping need to be able to deal with arbitrary pedigrees. In addition, these programs need to be able to handle incomplete penetrance. 3.5) What programs are used for chromosome mapping? [1995/05/31] CLINKAGE: This is the special version of the LINKAGE programs for 3-generation CEPH pedigrees and codominant markers. The PC and VAX versions are available by FTP from linkage.cpmc.columbia.edu. The Unix version is available from corona.med.utah.edu. CHROMLOOK: This is a program for generating haplotypes of marker data in nuclear pedigrees with all individuals genotyped. It identified both the maternal and paternal recombination events, and provides the resulting haplotypes and recombinants in an easy-to-read format. It should be available via FTP server sometime this summer. It was written by Jonathan Haines and he can be contacted at haines@helix.mgh.harvard.edu. CINTMAX: This program is an extensively modified version of CILINK. It uses map functions to model the transmission of gametes from parent to child. Some of these map functions are multilocus feasible, and so can be used with more than 3 loci at a time. It is available by anonymous FTP from watson.hgen.pitt.edu as cintmax.tar.Z. CRI-MAP: This program has been used for chromosome mapping for years. It has options which can generate maps, calculate order probabilities, and printout recombination data. It works on .gen files with data from CEPH style families. It is written in K&R type C code, and the author Phil Green has successfully ran it on Unix, DOS, VMS, and Macintosh systems. It is not available via anonymous FTP. Phil Green distributes CRI-MAP freely ONLY to academics/academic institutions. Contact him at: Phil Green; Molecular Biotechnology Dept., FJ-20; Fluke Hall on Mason Rd.; Univ. of Washington; Seattle, WA 98195; USA; Phone (206) 685-4341; Fax (206) 685-7344; or email phg@u.washington.edu. FASTMAP: This program produces quick approximation to multipoint lod score, available as a DOS executable and C source as fstmap11.zip from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. MULTIMAP: This LISP based expert system uses an customized version of CRI-MAP to create a chromosome map. It is available via anonymous FTP from chimera.gene.cwru.edu. The authors T. Matise, M. Perlin, and A. Chakravarti continue to improve the code, add new functions, and provide excellent support. When used with the CRI-MAP chrompic option (to find double-recombinations to identify possible errors), it is incredibly useful. This is Unix-only (supported for DEC-Ultrix, HP9000, and Suns). The customized CRI-MAP version (called LISPCRI) is distributed at the FTP site, but was not meant to be used independently of MULTIMAP. MAPMAKER: Dr. Eric Lander; Whitehead Institute; 9 Cambridge Center; Cambridge, MA 02142; mapm%mitwibr@mitvma.mit.edu. MAPMAKER is available via FTP at genome.wi.mit.edu in /pub/mapmaker3 3.6) What programs are used for disease gene mapping? [4/95] APM: The Affected Pedigree Member Method distribution contains the new APM programs, a new file conversion utility, and a histogram/statistics generator. To build the entire distribution, you need C, Pascal, and FORTRAN compilers, and a make utility is also helpful. The programs which are built include: APM, a program to calculate the single locus statistic over one or several marker loci; SIM, a program to simulate pedigrees and, using output files of APM, test for asymptotic normality of the null distribution; APMMULT, a program to generate the multilocus statistic; SIMMULT, a program like SIM but which simulates recombination and uses the output of APMMULT; CHAPM, a program to convert LINKAGE files to APM files, or APM files of one format to APM files of another format; and HIST, a program to compute various statistical figures, plot a histogram, and compute empirical p-values. The APMember package by D. Weeks is available via anonymous FTP from watson.hgen.pitt.edu. Additionally, there are pre-compiled executables of the APM programs for Sun-OS and Sun-Solaris available as newapm.sunos.tar.Z newapm.solaris.tar.Z. CLUMP: A Monte Carlo method for assessing significance of a case-control association study with a multi-allelic marker, available as DOS executable and C source. It is available as clump.zip via anonymous FTP from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. ESPA: This is a program used for extended sib pair analysis. It comes in a DOS version and can only look at markers containing 5 alleles. It was written by Lodeijk Sandkuijl and can be obtained by writing to him at Voorstraat 27; Delft 2611 JK; THE NETHERLANDS. ERPA: A program for carrying out nonparametric linkage analysis, available as DOS executable and C source. It is called erpa12.zip via anonymous FTP at ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. FASTLINK: This is a much faster implementation of the main programs in LINKAGE (LODSCORE, ILINK, MLINK, LINKMAP) in C. The code is faster due to the use of new and better algorithms for the time intensive parts of the computation. FASTLINK is distributed by A. A. Schaffer from the FTP site softlib.cs.rice.edu (cd pub/fastlink). Version 1 of FASTLINK was instigated by R. W. Cottingham Jr. with implementation done by R. M. Idury and A. A. Schaffer. Version 2 of FASTLINK includes further improvements implemented by A. A. Schaffer, S. K. Gupta, and K. Shriram, with guidance from R. W. Cottingham Jr. Version 2 includes the capability to recover gracefully from a crash of the computer on which FASTLINK is running. FASTLINK was initially intended for UNIX machines, but the distribution now includes instructions for porting to VMS as well as a version for DOS. FASTLINK allows you to compile in "fast" or "slow" mode (the slow version of FASTLINK is still much faster than the old LINKAGE programs). The "fast" version uses lots of memory, but uses the extra memory to contain some of the intermediate results which are repetitively recalculated in the "slow" version (and the old linkage package). Best speed can be obtained by setting up 300 megs of virtual memory on a Unix workstation and using the "fast" version. Schaffer maintains a mailing list of fastlink users (fastlink-list@cs.rice.edu) to answer queries and keep users up to date. Schaffer, Gupta, and other colleagues at Rice University have implemented parallel versions of FASTLINK for either a shared-memory multiprocessor or a network of UNIX workstations. Write to schaffer@cs.rice.edu for more information. GAS: It provides facilities for reading, writing, sectioning and performing statistical analyses on phenotypic and genotypic data and one of its features is sib pair analysis. It has been developed within the Department of Medicine at Oxford University and is available via FTP from well.ox.ac.uk in the directory pub/genetics/gas. GREGOR: It is a piece of DOS based software for producing simulated genetic data. It does not perform linkage analysis, but it may be useful for testing methods or assumptions about linkage analysis. GREGOR is operated by a series of hierarchical menus that permit the user to define hypothetical genetic scenarios (gene positions and effects) and produce simulated data-sets for a variety of population structures. GREGOR is available by FTP from the site sifon.cc.mcgill.ca in pub/McGill-Contrib. Questions should be directed to the authors tinker@agradm.lan.mcgill.ca or mather@agradm.lan.mcgill.ca. LINKAGE: This package of programs was developed by M. Lathrop with help from J. M. Lalouel, C. Jlier, and J. Ott. The LINKAGE package consists of several analysis and several utility programs. Versions are available for DOS, OS2, VAX, and Unix platforms. Here are some of the analysis programs: MLINK: 2-point lod-score calculations at fixed recombination distances; LINKMAP: multipoint lod score calculations at fixed distances; ILINK: calculates the recombination distance with the highest lod-score. Unix versions are available via gopher from corona.med.utah.edu in Publicly Accessible Software, probes(sts), etc./software/linkage, DOS and VMS versions are available from linkage.cpmc.columbia.edu, or on floppy disks, when you write to: Katherine Montague/Jurg Ott; Columbia University, Unit 58; 722 West 168th Street; New York, NY 10032. Send pre-formatted DOS disks if you request linkage by mail. You can send email to km165@columbia.edu if you need more information regarding mail requests for the LINKAGE package. LIPED: This DOS program written by J. Ott calculates probabilities for linkage between disease markers and genetic markers. Its input file differentiates between phenotypes and genotypes. As a result, this program is easiest to use when your data is from "old-style" genetic-markers (such as blood phenotype data). This was one of the first programs to do linkage analysis calculations, the LINKAGE package is more commonly used now. SAGE: Statistical Analysis Package for Genetic Epidemiology is composed of 18 programs: AGEON: Estimating the Distribution of Age-of-Onset, ASSOC: marker-trait Associations in Pedigree Data, BCROSS: Genetic Hypothesis for Quantitative Data on Inbred strains, their F1 and Backcross(es), CLUSTR: Power Transformation to Obtain Normality and Homoscedasticity from Clustered Data, FCOR: Family Correlations, FSP: Family Structure Program, LODLINK: Lod Score Linkage Analysis, MAPLOC: Mapping a Disease Related Trait Relative to a Set of Linked markers, MAXFUN: Function maximization Subroutine, REGC,REGD,REGTL,REGTN: Segregation Analysis Programs, RELATE: Relationship to Proband, SIBPAL: Sib-Pair Linkage Analysis, and DBSORT, RENUM, SPLIT: Toolkit Programs. Author Dr. R.C. Elston, address Department of Biometry and Genetics; Louisiana State University Medical Center; 1901 Perdido Street; New Orleans, Louisiana 70112, USA. The email contact address is sage@haldne.biogen.lsumc.edu. It is available for the following operating systems: VAX, SunOS 4.1.x, Apple Macintosh II, and DOS. This program is not shareware and must be bought. X-LINKED APM: X-linked version of the APM programs (single-marker), see APM above for more information on APM. It is available by anonymous FTP from watson.hgen.pitt.edu as xlinkapm.tar.Z. Also, xlinkapm.readm is available there, which is a readme about the X-linked version of the APM programs. 3.7) What programs are available for running linkage simulations? [1995/03/01] FASTSLINK: This is program is just like SLINK (see SLINK below), but it utilizes the enhancements incorporated into FASTLINK. It is available via anonymous FTP from watson.hgen.pitt.edu. SIMAPM: Is the SLINK based simulation program for the APM package. This represents a hacked together package which only runs under a Unix system. You will need FORTRAN, Pascal, and C compilers to use this package. It is available via anonymous FTP from watson.hgen.pitt.edu SIMLINK: This FORTRAN program developed by L. Ploughman and M. Boehnke simulates linkage analysis on a family, and gives you an estimate the probability, or power, of detecting linkage in a given family. It allows the researcher to determine whether a family has sufficient informativeness to detect linkage. SIMLINK requires large quantities of memory. It was written for DOS, but has been ported to many platforms. It is available from: Michael Boehnke; Department of Biostatistics; School of Public Health; University of Michigan; Ann Arbor, MI 48109-2029. No postage-money or blank disks are necessary to get SIMLINK sent to you. SIMLINK may be available via anonymous FTP soon. For further information send email to michael.boehnke@um.cc.umich.edu. SLINK: It is a Pascal program developed by D. Weeks, M. Lathrop, and J. Ott. It is similar to SIMLINK. It is more general than SIMLINK in that it allows for partial marker typing at the locus to be generated, but it runs slower than SIMLINK. It is available from linkage.cpmc.columbia.edu and watson.hgen.pitt.edu or on floppies (use the same address as for LINKAGE). 3.8) What programs are available to help detect errors in linkage data? [1995/03/01] Typically the linkage packages in and of themselves will detect errors in linkage data that are obvious, such as impossible phenotypes and genotypes, and obvious errors in pedigrees. Typically the programs will just grind to halt and allow you to fix the error, and try again until you finally succeed. However, errors that “make sense” to linkage programs will not be detected. 3.9) What programs help me recode genetic markers? [1995/03/01] DOLINK can downcode alleles automatically. However, the main use of DOLINK is to prepare files for LINKAGE from a database. In addition P. Adams package LABMAN and LINKMAN have features for the recoding of alleles. 4.0) LINKAGE PACKAGE SPECIFIC INFORMATION 4.1) How do I get my CEPH data into CRI-MAP format? [1995/03/01] You can output the file in linkage format and use link2gen in CRI-MAP. The disadvantage here is that your marker names are separated from your data and it’s easy to make a mistake and get them mixed up. You can output the file in ped.out format and use CEPH2CRI mentioned above in the FAQ to do the conversion as well. 4.2) How do you calculate MAXHAP? [1995/03/01] MAXHAP is the maximum possible number of haplotypes in your analysis. You multiply together the number of alleles at each locus used in a particular run; not all loci in your dataset, just the loci you are using in that particular calculation. Remember that the affection status counts as two alleles, regardless of the number of liability classes. For example, if a dataset has the following information: the liability classes, marker A has 3 alleles, marker B has 4 alleles, and marker C has 5 alleles and your run includes a LINKMAP run between affection status, marker A, and marker B, then your MAXHAP must be at least 2*3*4=24. 4.3) When should you use binary coding instead of numeric allele coding? [1995/03/01] Usually there is no advantage to coding disease loci as either binary or numeric using liability classes. Generally, binary coding is more complex in that we humans often have a hard time thinking that way. Some of the codominant phenotypes lend themselves to binary coding; for example, ABO blood types: A (101), B (011), O (001), AB (111), and unknown (000). Since you cannot distinguish AO from AA at the phenotype level you code both genotypes as (101), presence of A and O. In reality O represents absence of both A and B. However, do not code using (000), since it would be an unknown. Use of binary codes has decreased since DNA markers have come into use since they allow one to type an individual with respect to genotype. You can use binary codes if you have phenotypic data which does not allow for the discrimination of the underlying genotype exactly, and one can code it as the presence with 1 or absence with 0 of factors such as the A and B antigens. Binary codes allow the representing loci with codominant and dominant mode of inheritance, while allele number notation is good only for codominant loci. Few people use binary factor notation. They either use allele numbers for codominant loci, or affection status notation for dominant loci. The main reason why binary factor notation is still currently used is that CEPH’s database is in that notation. 4.4) What do you do when allele frequencies not add up to 1, for example, when alleles are not present in a pedigree under study? [1995/03/01] The best approach is to specify n+1 alleles, where there are n alleles actually observed in the pedigree. Use the correct allele frequencies for the n alleles, and for the n+1 allele, use 1 minus the sum of the frequencies of the observed alleles. 4.5) I use LINKAGE and/or FASTLINK, what references should I cite in my papers? [1995/03/01] FASTLINK users should cite: Cottingham, R. W. Jr., Idury, R. M., and Schaffer, A. A. “Faster Sequential Linkage Computations.” American Journal of Human Genetics. 53:252-263, 1993. Schaffer, A. A. , Gupta, S. K., Shriram, K., and Cottingham, R. W. Jr. “Avoiding Recomputation in Linkage Analysis”. Human Heredity. 44(4):225-37, 1994 Jul-Aug. In addition, all FASTLINK and LINKAGE users should also cite the LINKAGE papers: Lathrop, G.M., Lalouel, J.M., Julier, C. , and Ott, J. “Strategies for Multilocus Analysis in Humans.” PNAS. 81:3443-3446, 1984. Lathrop, G.M. and Lalouel, J.M., “Easy Calculations of LOD Scores and Genetic Risks on Small Computers.” American Journal of Human Genetics. 36:460-465, 1984. Lathrop, G.M., Lalouel, J.M., and R. L. White. “Construction of Human Linkage Maps: Likelihood Calculations for Multilocus Analysis.” Genetic Epidemiology. 3:39-52, 1986. 4.6) What is recoding of alleles all about anyway? [1995/03/01] One of the problems with highly polymorphic markers is that they can increase the computational requirements of the computers by several orders of magnitude due to the large number of alleles present. This can put the computation of some lod scores out of reach for DOS computers and take many days on higher end systems. So it is important to use methods that reduce the number of alleles, and recoding will reduce the number of alleles in your calculations. The method of recoding of alleles described by J. Ott in the Annals of Human Genetics, 42:255-257 (1978) works very well, but can only be done when the mode of inheritance of the disease is known. An article inspired by Ott’s original work written M. Braverman in Computers and Biomedical Research, 18:24-36 (1985) extends the recoding of alleles in two ways: 1) it allows for pedigrees of arbitrary structure, and 2) it allows for missing/partially known marker phenotypes. It is usually possible to recode marker alleles to some extent even if the mode of inheritance of the disease is not known since what is still desired with respect to the marker is a labeling which preserves the available information about the source of each marker allele. It is important, however, where the full ancestry of alleles cannot be traced in a pedigree, that the recoded alleles maintain the allele frequencies appropriate to the original alleles. In a complex disorder, this may not be possible. Another method is if the marker in question has 14 alleles in the general population, but only 9 alleles in the study population, it is possible to collapse the functional number of alleles to 9 or 10. Usually, adjust the allele frequencies to sum to 1 by dividing each allele frequency by the sum of the (observed) allele frequencies. For the latter all the allele frequencies remain the same, but the unobserved ones are collapsed into a single allele (and frequency). If there are 9 observed alleles (but there are 14 in the population), then rescaling the frequencies of the observed 9 alleles will also not produce quite correct results. Consider the unlikely example of a huge pedigree with only the most recent generation observed in which the observed 9 alleles all have very low and equal frequency. If there are distantly separated relatives who are affected there is some reasonable support for linkage since the alleles are rare. But if we rescale frequencies to 1/9 per alleles, then sharing of alleles isn't so unlikely. Coding the marker with 10 alleles produces correct results as it will produce the same lod scores as would coding the marker with 14 alleles. 5.0) COMPUTER ADMINISTRATION AND OPTIMIZATION 5.1) How can I increase the speed of the LINKAGE/FASTLINK package on my workstation? [1995/05/18] 1. Use FASTLINK, which is the C version of the LINKAGE package with a few algorithmic improvements. It can increase the speed of your calculations by an order of magnitude. 2. Setting up lots of paging space, which uses the hard drive as virtual memory (300 megs is usually plenty). Note that paging space is the same as swap space. Then use the "fast" versions of FASTLINK. 3. Use GCC, which is the GNU/Free Software Foundation C compiler, to compile FASTLINK. GCC produces machine language that is about 10% faster than Sun's C compiler. 4. Install the generic small kernel instead of the generic kernel. The generic kernel has device files for almost everything, and can slow the system down. The generic small kernel is configured for a system without many devices and without many users. Installing a generic small kernel is an option during system installation on Sun workstations. 5. Reconfigure your kernel so it has only devices you need. This should give you a small improvement in overall system speed, but if you are already running the generic-small kernel, additional improvement may be so small that it's not worth the trouble. If the generic small kernel is insufficient for your system this step is a must. The generic kernel will slow down your workstation significantly and most of the device support is unnecessary. 6. Don't run your linkage analyses in the background, because running programs in the background gives them a lower priority. Either do the runs in the foreground or you can use the root password to nice the pedin process by -3 to compensate (negative nice values give a higher priority). If you need to log out, you can use the screen command and "detach" a session so you can log out without programs terminating. Later you can log back in and "reattach" the session, which continued to run while you were logged out. The screen command is available at prep.ai.mit.edu and is also on the O'Reilly Unix Power Tools CD- ROM. According to the Sun documentation, nicing below -10 can interfere with the operating system and actually reduce the process' speed. Running them at the standard default level of 0 is usually sufficient. Some people recommend to run a background job to using nice +19 (!). In this way, the job will not interfere with other normal processes like login. 7. Runs with 100% penetrance can run faster than runs with incomplete penetrance. Of course, if you have an unaffected obligate carrier, this won't work. In addition, incomplete penetrance runs may be necessary for your research to be "good". 8. Change the block size of your file system. One can increase performance of a file system by increasing the block size, thus decreasing the number of read-write operations. A block device, such as a hard disk, usually accesses a block of data simultaneously. Thus, if one is expecting to use large files, having large blocks will be an advantage. However, one usually trades the number of bytes lost to partial files since one has to increase the fragment size to a number larger than 1024, for example 2048. That is, each file or part of a file occupies 2048 bytes, a file of 100 bytes will still occupy 2048 bytes. Therefore, bigger blocks give faster bigger blocks with bigger fragments and more lost space. 9. It has been noted that you can increase the speed of programs which create/access large files in the /tmp directory by creating a tmpfs file system. 10. Of course, buying more RAM will increase your speed. It’s been said that increasing RAM from 16 to 32 megs will result in a large increase in speed and increasing RAM from 32-64 megs will result in a significant increase. However, increasing beyond 64 megs is not particularly helpful. From owner-gene-linkage@net.bio.net Tue Aug 08 23:00:00 1995 Path: biosci!daresbury!nntp-trd.UNINETT.no!Norway.EU.net!EU.net!howland.reston.ans.net!newsjunkie.ans.net!news.agt.net!news.planet.eon.net!news From: brian fitzsimons Newsgroups: bionet.molbio.gene-linkage Subject: information on medical research Date: 9 Aug 1995 02:44:48 GMT Organization: Public Live Access Network (PLAnet) Lines: 7 Message-ID: <4097f0$nji@tigger.planet.eon.net> NNTP-Posting-Host: 204.209.176.228 Would you like to know about some of the latest research on painful knees? Living Wills? The Genetics of Cancer? Or other health concerns? Look up the new Alberta Heritage Foundation for Medical Research website. The AHFMR is dedicated to research and development in the medical and scientific fields. http://www.sas.ab.ca/ahfmr From owner-gene-linkage@net.bio.net Tue Aug 08 23:00:00 1995 Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!newsjunkie.ans.net!news.agt.net!news.planet.eon.net!news From: brian fitzsimons Newsgroups: bionet.molbio.gene-linkage Subject: Information on medical research Date: 9 Aug 1995 02:43:04 GMT Organization: Public Live Access Network (PLAnet) Lines: 7 Message-ID: <4097bo$nhn@tigger.planet.eon.net> NNTP-Posting-Host: 204.209.176.228 Would you like to know about some of the latest research on painful knees? Living Wills? The Genetics of Cancer? Or other health concerns? Look up the new Alberta Heritage Foundation for Medical Research website. The AHFMR is dedicated to research and development in the medical and scientific fields. http://www.sas.ab.ca/ahfmr From owner-gene-linkage@net.bio.net Wed Aug 09 23:00:00 1995 Path: biosci!daresbury!not-for-mail From: "Lucerna genetika csoport" Newsgroups: bionet.molbio.gene-linkage Subject: linkage map of pea Date: 10 Aug 1995 11:33:10 +0100 Organization: Biological Research Center Lines: 18 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <40cn96$p15@mserv1.dl.ac.uk> X-Pmuue: MAPPIS.LEV Original-To: gen-link@dl.ac.uk X-Finfo: DOS,"MAPPIS.LEV",,,, * This message contains the file 'MAPPIS.LEV', which has been * uuencoded. If you are using Pegasus Mail, then you can use * the browser's eXtract function to lift the original contents * out to a file, otherwise you will have to extract the message * and uudecode it manually. begin 660 MAPPIS.LEV M1&5A6)O9'D@:&5L<"!M92!T;R!G970@ M82!R96QA=&EV92!N97<@=F5R&-E<'1I;VX@16QL:7,@970@86PN("@Q.3DR*2!'96YE M=&EC"`U,C$@2"TV-S`Q("`@("`@("`@("`@("`@(`T*:V%L-S,S-D!H96QK82YI E:68N:'4@;W(@86QF:4!E=F5R>"YS>F)K+G4M Discarded-X400-IPMS-Extensions: ccitt (0) data (9) pss (2342) (2342) (19200300) (200) (1) Original-To: gen-link@dl.ac.uk Dear Netters, Can anybody help me to get a relative new version of linkage map of Pisum sativum exception Ellis et al. (1992) Genetics 130:649-663? Thanks a lot, Peter Kalo Biological Research Center of Hungarian Academy of Sciences Institute of Genetics P.O. Box 521 H-6701 kal7336@helka.iif.hu or alfi@everx.szbk.u-szeged.hu From owner-gene-linkage@net.bio.net Wed Aug 09 23:00:00 1995 Path: biosci!daresbury!not-for-mail From: h7336kal@ella.hu Newsgroups: bionet.molbio.gene-linkage Subject: linkage map of pea Date: 10 Aug 1995 18:44:39 +0100 Lines: 12 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <40dgi7$i7p@mserv1.dl.ac.uk> Discarded-X400-IPMS-Extensions: ccitt (0) data (9) pss (2342) (2342) (19200300) (200) (1) Original-To: gen-link@dl.ac.uk Dear Netters, Can anybody help me to get a relative new version of linkage map of Pisum sativum exception Ellis et al. (1992) Genetics 130:649-663? Thanks a lot, Peter Kalo Biological Research Center of Hungarian Academy of Sciences Institute of Genetics P.O. Box 521 H-6701 kal7336@helka.iif.hu or alfi@everx.szbk.u-szeged.hu From owner-gene-linkage@net.bio.net Wed Aug 09 23:00:00 1995 Path: biosci!ns1.faseb.org!darwin.sura.net!mother.usf.edu!news From: tabibzadeh@rics.moffitt.usf.edu (SIAMAK TABIBZADEH) Newsgroups: bionet.molbio.gene-linkage Subject: Frontiers in Bioscience, a journal and virtual library Date: 10 Aug 1995 14:28:16 GMT Organization: Moffitt Cancer Center at USF Lines: 40 Message-ID: <40d521$73c@mother.usf.edu> NNTP-Posting-Host: pc3160.moffitt.usf.edu Mime-Version: 1.0 X-Newsreader: WinVN 0.93.11 Frontiers in Bioscience, a journal and virtual library An electronic journal and virtual library has been created in order to facilitate rapid dissemination of scientific data as well as to provide investigators with numerous online tools for use in their day-to-day research activities. The publication cost is minimized or completely eliminated. A section of the journal is dedicated to publishing manuscripts that contain real time events. Access to a large number of databases is quite easy from the journal. These include databases for analysis of scientific data, search strategies, dictionaries, atlases, tutorials, conferences, information on products of various manufacturers, links to online journals and many other valuable information. Access to the journal and these services is free. The staff members of the journal are in the process of creation of various databases. One such database on gene knockout is already online. The journal can be accessed at the following address on WWW: http://bayanet.com/bioscience Although submission of data for publication in electronic platforms has just begun, this method of distribution of scientific information would certainly be the logical route of the future. The first volume of the journal to be published around Jan 1996 will contain excellent manuscripts. Please take a moment to examine the journal and consider to send manuscripts for publication in this new and novel forum. The address of the editorial office is as follows: Frontiers in Bioscience S Tabibzadeh, MD, Dept of Pathology University of South Florida 12901 Bruce B Downs Blvd Tampa, FL 33612 Tel: 813-979-7237 Fax: 813-979-3085 E-mail: tabibzadeh@rics.moffitt.usf.edu From owner-gene-linkage@net.bio.net Wed Aug 09 23:00:00 1995 Path: biosci!daresbury!nntp-trd.UNINETT.no!nac.no!Norway.EU.net!EU.net!newsfeed.internetmci.com!news.sprintlink.net!uunet!in2.uu.net!news.vanderbilt.edu!NewsWatcher!user From: goldenjb@ctrvax.vanderbilt.edu (Jim Golden) Newsgroups: bionet.molbio.gene-linkage Subject: Looking for info on DataGenetics Followup-To: bionet.molbio.gene-linkage Date: 10 Aug 1995 19:53:01 GMT Organization: Vanderbilt Lines: 8 Message-ID: NNTP-Posting-Host: 129.59.170.62 We're looking for some information on a company in the Bay area called DataGenetics. Has anyone heard of them? Do they have a web site? They offer genotyping services at prices well below the competition and we're interested in learning a little more about them. Please e-mail me. Jim Golden goldenjb@ctrvax.vanderbilt.edu Vanderbilt School of Medicine From owner-gene-linkage@net.bio.net Tue Aug 15 23:00:00 1995 Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!gatech!usenet.eel.ufl.edu!interlog.com!news1.fonorola.net!geac!lethe!abyss!news2.compulink.com!binh Newsgroups: bionet.molbio.gene-linkage From: binh@cml.com (binh) Subject: test, please ignore X-Newsreader: TIN [version 1.2 PL2] Organization: ComputerLink Online Inc. X-Client-Port: 4038 Message-ID: X-Nntp-Posting-Host: cml.com Date: 16 Aug 95 12:40:22 GMT Sender: binh@cml.com Lines: 4 test. Aug 16, 9:20 am. ------------------------------------------------------------------------- : ComputerLink Online (416)233-5410 104 lines, SLIP, 9600 - 28,800 bps : ------------------------------------------------------------------------- From owner-gene-linkage@net.bio.net Tue Aug 15 23:00:00 1995 Path: biosci!internet!biosci!not-for-mail From: biohelp (BIOSCI Administrator) Newsgroups: bionet.molbio.gene-linkage Subject: UNSUBSCRIBING, BIOSCI ARCHIVES, ADDRESS DATABASE & BIOSCI FAQ Date: 16 Aug 1995 02:00:23 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 347 Sender: daemon@net.bio.net Distribution: world Message-ID: <199508160900.CAA01960@net.bio.net> NNTP-Posting-Host: net.bio.net Four important items follow: How to cancel e-mail subscriptions to BIOSCI newsgroups, BIOSCI archive searching, the BIOSCI FAQ, and the BIOSCI User Address Directory form. If you have not yet listed yourself in our BIOSCI user directory, please take a few minutes to complete and return the form below. If your personal information has changed since you listed yourself, please send us a complete new updated form. We can not make manual revisions to existing entries. Sincerely, Dave Kristofferson BIOSCI/bionet Manager biosci-help@net.bio.net **** How to cancel a BIOSCI e-mail subscription **** If you want to cancel your e-mail subscription to this group, PLEASE DO NOT POST YOUR UNSUBSCRIBE REQUEST TO THE NEWSGROUP ADDRESS (NOR REPLY TO A MESSAGE POSTED TO THE NEWSGROUP)!!! This would send your request to all of the readers of the newsgroup, but it might still not be seen by the BIOSCI staff - thus you would annoy many people and possibly not accomplish your goal anyway. IF YOU ARE LOCATED IN THE AMERICAS OR PACIFIC RIM COUNTRIES, please send a message to biosci@net.bio.net Instructions on how to subscribe/unsubscribe will be returned automatically, so the contents of your message do not matter. IF YOU ARE LOCATED IN EUROPE, AFRICA OR CENTRAL ASIA, please send a message to MXT@dl.ac.uk containing the word help in the body of the message to retrieve e-mail server instructions. Any text placed on the Subject: line of your message will be ignored, so be sure to put the "help" command in the body of the message. If you need personal assistance, a BIOSCI staff member can be contacted at either of the following addresses. Please contact the address designated for your location. Support Address Location --------------- -------- biosci@daresbury.ac.uk Europe, Africa, and Central Asia biosci-help@net.bio.net Americas and the Pacific Rim **** SEARCHING BIOSCI ARCHIVES **** The easiest way to search the BIOSCI archives is to use Mosaic or another World Wide Web browser and connect to the BIOSCI WWW home page at URL http://www.bio.net/. Select the hypertext link to the BIOSCI archives. This gives you read access to all newsgroup messages and the ability to search the indexes described below. You can also use gopher software and connect over the Internet to net.bio.net, the U.S. BIOSCI computer. We maintain three indexes which are searchable from the main gopher menu on net.bio.net: (1) an index of all BIOSCI postings; (2) an index of individual journal article references from the Table of Contents postings on the BIO-JOURNALS newsgroup; and (3) an index of BIOSCI users including regular mail and e-mail addresses, phone/FAX numbers, research interests, and newsgroup participation. E-mail users can search the BIOSCI archives by using our waismail e-mail server. For instructions send the message help to waismail@net.bio.net. Leave the Subject: line blank (anything entered on the Subject: line is ignored). WAIS software can also be used to search the archives as described in the BIOSCI FAQ (see below). Finally, the BIOSCI archive files are accessible by anonymous FTP to net.bio.net [134.172.2.69] in the directory pub/BIOSCI. **** BIOSCI FREQUENTLY ASKED QUESTIONS (FAQ) SHEET **** New users of BIOSCI/bionet may want to read the "Frequently Asked Questions" or "FAQ" sheet for BIOSCI. The FAQ provides details on how to participate in these forums and fix problems that you might encounter in using the newsgroups. The FAQ and other BIOSCI documentation is available through our WWW home page at URL http://www.bio.net/. It is also available for anonymous FTP from net.bio.net [134.172.2.69] in pub/BIOSCI/doc/biosci.FAQ or for retrieval by gopher to net.bio.net, port 70. It may also be requested by sending the command info faq in the body of an e-mail message to the Internet address biosci-server@net.bio.net. Please do not enter the info faq command on the Subject: line of your message since the e-mail server ignores text on the Subject: line. The FAQ is also posted on the first of each month to the newsgroup BIONEWS/bionet.announce immediately following the posting of the BIOSCI information sheet. **** BIOSCI USER ADDRESS DIRECTORY **** Please take this opportunity to add your name and address information to the BIOSCI User Address Database if you have not already done so. Below is the address form that we would like each reader of the BIOSCI/bionet newsgroups to complete and return if you would like to be listed in our database. The database serves as a directory that enables biologists, who are currently using (or even just reading) the BIOSCI newsgroups, to look up e-mail addresses and other information about our users. The address database is reindexed nightly for WAIS, waismail, gopher, and WWW access (the URL is http://www.bio.net). If you have access to gopher, connect to net.bio.net to search the database. If you have access to WAIS, please use our WAIS source biologists-addresses.src. If you are not on the Internet, please use our waismail server (send the word "help" to waismail@net.bio.net to get instructions; any text on the Subject: line of your message will be ignored, so put the help command in the body of the mail message.). Please carefully follow the instructions for completing the form below and return it to either of the following two addresses (whichever is more convenient for you). Thanks in advance for taking the time to complete and return the form. Addresses for returning forms Location Network ----------------------------- -------- ------- biovote@net.bio.net U.S.A. Internet/BITNET biovote@daresbury.ac.uk U.K. JANET MAKING SURE THAT YOUR INFORMATION IS CURRENT This notice will be mailed bimonthly to each newsgroup. You should check your database entry from time-to-time to see if your address information is still up-to-date. Using Gopher to complete the form --------------------------------- If you don't want to use a text editor, you can also use Dan Jacobson's gopher site to fill out the address database form as follows. Otherwise skip this section on gopher and proceed to the instructions for filling out the form below. > To add yourself to the database just point your > gopher client at merlot.gdb.org and select the following: > > --> 14. Searching For Biologists/ > > --> 9. E-mail Addresses of Biosci-Bionet Users/ > > --> 1. Add (or Correct) Your Address to the BIOSCI User Address > Data.. > > > And fill out the form. or Rob Harper's gopher site in Europe as follows: > Europeans can point their gopher client at gopher.csc.fi and add their > information to the database. All entries will be mailed directly to > Dave for incorporation in a wais source. > > The path to the questionare is as follows. > > > 6. Information in English/ > > 5. Scientific and other topics/ > > 1. Finnish EMBnet BioBox/ > > 9. FAQ Files/ > > 5. Bionauts Address Database (questionaire) > IMPORTANT INSTRUCTIONS - PLEASE READ CAREFULLY Please enter all responses after the : on each line, leaving one (1) blank space after the : (i.e., before the start of your text). Please do NOT extend your responses past the end of each line (80 characters). PLEASE DO NOT alter any of the field identifiers such as "first name: ". If you have nothing to enter after a field identifier, PLEASE LEAVE IT - do not delete it even if there is no data on the line in question. Several lines are provided at the end of the form for comments, but, please adhere to the line length restriction. On the date: line, please enter the date in the DD-MM-YY format, e.g., 15-05-93 for 15 May 1993. This line will tell others when the information was last updated. Please be sure to include the 0's for single digit days or months, e.g., 15-05-93, not 15-5-93. Note that the "e-mail network: " line below is for specifying, e.g., "Internet," "BITNET," "EARN," "JANET," or whatever other network that your computer may be on. If you are uncertain about any field, please feel free to leave it blank, but please DO NOT DELETE the field identifier from the form! In the first field below, "New information or Update ...", please enter "N" if this is the first time that you have registered in the directory or "U" if you are correcting a listing that you sent to us previously. The comment: lines may be used for anything that you like but PLEASE DO NOT DELETE THEM FROM THE FORM OR ALTER THEM. One suggested use is to list the names of the newsgroups in which you participate. Please use the MAILING LIST name (see below - the latest version of the list can be requested from biosci@net.bio.net) instead of the USENET name even if you don't participate by e-mail. WAIS might get confused by the periods in the USENET names. This allows one to retrieve via WAIS or waismail the list of participants in a particular group. For example: comment: ARABIDOPSIS PLANT-BIOLOGY BIONEWS On the comment: lines use these names below ---- NOT the USENET names below MAILING LIST NAME USENET Newsgroup Name ----------------- --------------------- ACEDB-SOFT bionet.software.acedb AGEING bionet.molbio.ageing AGROFORESTRY bionet.agroforestry ARABIDOPSIS bionet.genome.arabidopsis ASCB bionet.prof-society.ascb BIOCAN bionet.prof-society.cfbs BIOFORUM bionet.general BIO-INFORMATION-THEORY bionet.info-theory BIONAUTS bionet.users.addresses BIONEWS bionet.announce BIO-JOURNALS bionet.journals.contents BIO-MATRIX bionet.molbio.bio-matrix BIOPHYSICAL-SOCIETY bionet.prof-society.biophysics BIOPHYSICS bionet.biophysics BIO-SOFTWARE bionet.software BIOTHERMOKINETICS bionet.metabolic-reg BIO-WWW bionet.software.www CARDIOVASCULAR-RESEARCH bionet.biology.cardiovascular CELEGANS bionet.celegans CELL-BIOLOGY bionet.cellbiol CHLAMYDOMONAS bionet.chlamydomonas CHROMOSOMES bionet.genome.chromosomes COMPUTATIONAL-BIOLOGY bionet.biology.computational CSM bionet.prof-society.csm CYTONET bionet.cellbiol.cytonet DROSOPHILA bionet.drosophila EMBL-DATABANK bionet.molbio.embldatabank EMF-BIO bionet.emf-bio EMPLOYMENT bionet.jobs EMPLOYMENT-WANTED bionet.jobs.wanted FASEB bionet.prof-society.faseb GDB bionet.molbio.gdb GENBANK-BB bionet.molbio.genbank GENETIC-LINKAGE bionet.molbio.gene-linkage GRASSES-SCIENCE bionet.biology.grasses HIV-MOLECULAR-BIOLOGY bionet.molbio.hiv HUMAN-GENOME-PROGRAM bionet.molbio.genome-program IMMUNOLOGY bionet.immunology INFO-GCG bionet.software.gcg JOURNAL-NOTES bionet.journals.note METHODS-AND-REAGENTS bionet.molbio.methds-reagnts MICROBIOLOGY bionet.microbiology MOLECULAR-EVOLUTION bionet.molbio.evolution MOLECULAR-MODELLING bionet.molec-model MOLLUSC-MOLECULAR-NEWS bionet.molbio.molluscs MYCOLOGY bionet.mycology NEUROSCIENCE bionet.neuroscience N2-FIXATION bionet.biology.n2-fixation PARASITOLOGY bionet.parasitology PHOTOSYNTHESIS bionet.photosynthesis PLANT-BIOLOGY bionet.plants POPULATION-BIOLOGY bionet.population-bio PROTEIN-ANALYSIS bionet.molbio.proteins PROTEIN-CRYSTALLOGRAPHY bionet.xtallography PROTISTA bionet.protista RAPD bionet.molbio.rapd SCIENCE-RESOURCES bionet.sci-resources STADEN bionet.software.staden STRUCTURAL-NMR bionet.structural-nmr TROPICAL-BIOLOGY bionet.biology.tropical URODELES bionet.organisms.urodeles VIROLOGY bionet.virology WOMEN-IN-BIOLOGY bionet.women-in-bio YEAST bionet.molbio.yeast ZBRAFISH bionet.organisms.zebrafish Listing newsgroups on the comment: line is optional, of course. Thanks again for your cooperation! --------------- please cut here and return portion below --------------- New information or Update to old record (enter N or U): date (DD-MM-YY): first name: middle initial: family name: job title: e-mail address: e-mail network: phone number: FAX number: institution: address1: address2: address3: city: state/province: country: postal code: research interest: research interest: comment: comment: comment: comment: comment: From owner-gene-linkage@net.bio.net Wed Aug 16 23:00:00 1995 Path: biosci!daresbury!nntp-trd.UNINETT.no!Norway.EU.net!EU.net!howland.reston.ans.net!news.moneng.mei.com!bloom-beacon.mit.edu!boulder!christina.Colorado.EDU!stalling From: stalling@ibg.colorado.edu (Michael Stallings) Newsgroups: bionet.molbio.gene-linkage Subject: Ott's Linkage program for DEC Alpha? Date: 16 Aug 1995 22:38:49 GMT Organization: University of Colorado, Boulder Lines: 8 Message-ID: <40ts1p$ivr@CUBoulder.Colorado.EDU> NNTP-Posting-Host: christina.colorado.edu Has anyone been able to successfully compile Preplink, which is part of Ott's Linkage package, for the DEC Alpha? It compiles without error on both our DEC Alpha and our DEC Ultrix machines, but the input/output options don't work with either binary. Any info/help would be greatly appreciated! -- Michael.Stallings@Colorado.EDU From owner-gene-linkage@net.bio.net Wed Aug 16 23:00:00 1995 Path: biosci!daresbury!not-for-mail From: Lucien Bachner Newsgroups: bionet.molbio.gene-linkage Subject: Re: Ott's Linkage program for DEC Alpha? Date: 17 Aug 1995 10:02:34 +0100 Lines: 6 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <40v0ja$ils@mserv1.dl.ac.uk> Original-To: stalling@ibg.colorado.edu You can use the i/o options by renaming/copying the input/output files as indata/oudata if I remenber well. You can verify the name by using the option "write file" and checking the name of the new file created (read outdata 2 lines before) Hope it's clear enough. Lucien Bachner From owner-gene-linkage@net.bio.net Wed Aug 16 23:00:00 1995 Path: biosci!bcm!pendragon.jsc.nasa.gov!news.msfc.nasa.gov!newsfeed.internetmci.com!news.sprintlink.net!howland.reston.ans.net!tank.news.pipex.net!pipex!oleane!jussieu.fr!univ-lyon1.fr!swidir.switch.ch!scsing.switch.ch!aragorn.unibe.ch!itzbaeumle.unibe.ch!BAEUMLE From: BAEUMLE@itz.unibe.ch (Etienne Baeumle) Newsgroups: bionet.molbio.gene-linkage Subject: Re: Ott's Linkage program for DEC Alpha? Date: Thu, 17 Aug 1995 08:55:37 GMT Organization: University of Berne, Switzerland Lines: 19 Message-ID: References: <40ts1p$ivr@CUBoulder.Colorado.EDU> NNTP-Posting-Host: itzbaeumle.unibe.ch X-Newsreader: Trumpet for Windows [Version 1.0 Rev A] >Has anyone been able to successfully compile Preplink, which is part >of Ott's Linkage package, for the DEC Alpha? It compiles without >error on both our DEC Alpha and our DEC Ultrix machines, but the >input/output options don't work with either binary. Any info/help >would be greatly appreciated! >Michael.Stallings@Colorado.EDU I have the same problems. If you hear anything about this it would be great, if you can put it here! Thank you. Etienne. -------------------------------------------------------------------- Etienne Baeumle, Institute of Animal Breeding, University of Berne Bremgartenstrasse 109a, CH-3012 Berne, Switzerland Phone: ++41 (0)31 631 23 38, Fax: ++41 (0)31 631 26 40 RFC: baeumle@itz.unibe.ch, X.400: S=baeumle; OU=itz; O=unibe; P=switch; A=arcom; C=ch -------------------------------------------------------------------- From owner-gene-linkage@net.bio.net Thu Aug 17 23:00:00 1995 Path: biosci!bloom-beacon.mit.edu!news.moneng.mei.com!news.ecn.bgu.edu!vixen.cso.uiuc.edu!howland.reston.ans.net!tank.news.pipex.net!pipex!sunsite.doc.ic.ac.uk!hgmp.mrc.ac.uk!fvisser From: fvisser@hgmp.mrc.ac.uk (Frank Visser) Newsgroups: bionet.molbio.gene-linkage Subject: MLINK: impossible result? Date: 18 Aug 1995 12:58:16 GMT Organization: MRC Human Genome Resource Centre Lines: 50 Message-ID: <4122p8$q03@mercury.hgmp.mrc.ac.uk> NNTP-Posting-Host: sodium.hgmp.mrc.ac.uk Keywords: MLINK, linkage X-Newsreader: TIN [version 1.2 PL2] Hello, I received a query from a user regarding some results he got when doing a two-point linkage analysis. Here follows the query: ----- I have a problem with a simple two point linkage analysis. I have done many such analyses in the past and experience has taught me to expect that, with any fully penetrant dominant phenotype, a marker that detects a crossover will always give negative infinity at a theta of zero. However I now have a family with about 40 meioses in 60 or so individuals in which this is not happening. Is this possible? The single crossover is between branches of the family separated by seven unsampled meioses (the people involved are dead) but it is quite unambiguously there. The disease segregates with one allele in all the rest of the family and with another in a small branch. This is only clearly visable in two individuals but nevertheless it is there.The lod score in question rises to a peak of over 5 at about three centimorgans then falls to 3.4 at zero. I've checked it, I've run it on both a PC and the HGMP facility, I've played with allele frequencies of both the linked marker and the disease, I've run both two point (MLINK) and multipoint (LINKMAP), I've even typed the whole thing in again from scratch, and still it is there. The lod score goes up and down, but is always still posative at a theta of zero. Have I made a mistake, or is this a real result? Any help or advice would be gratefully recieved. ----- So, is it possible to get such a result for a fully penetrant dominant phenotype? Or is more detailed knowledge of the pedigree necessary? Is something wrong with the model? I tried to figure it out for myself but am not sure. Intuitively I would say that something is wrong, but I do not have any idea where to start to look. Any information, discussion, pointers to literature, etc. gladly welcomed. All information will be passed on to the user. Frank ---- F. R. Visser HGMP-Resource Centre Hinxton, UK Phone : +44 (0)1223 494526 e-mail: fvisser@hgmp.mrc.ac.uk From owner-gene-linkage@net.bio.net Thu Aug 17 23:00:00 1995 Path: biosci!daresbury!hgmp.mrc.ac.uk!fvisser From: fvisser@hgmp.mrc.ac.uk (Frank Visser) Newsgroups: bionet.molbio.gene-linkage Subject: Re: MLINK: impossible result? Date: 18 Aug 1995 15:02:47 GMT Organization: MRC Human Genome Resource Centre Lines: 143 Message-ID: <412a2n$q03@mercury.hgmp.mrc.ac.uk> References: <4122p8$q03@mercury.hgmp.mrc.ac.uk> <412811$t4l@mercury.hgmp.mrc.ac.uk> NNTP-Posting-Host: sodium.hgmp.mrc.ac.uk X-Newsreader: TIN [version 1.2 PL2] I. Fenton (ifenton@hgmp.mrc.ac.uk) wrote: : [snip, snip - discussion of possibly weird mlink result] : my random thoughts... could the DATAIN.DAT file be posted, so that : we can see exactly how the disease and/or liability classes have : been set up. there may be something subtle in there that you're : not spotting. also a lod-score table and/or PEDIN.DAT may help us. OK, here follows: datain.dat: -------- 4 0 0 1 << no loci, risk locus, sexlinked(if 1) 0 0.0 0.0 0 << mut locus, mut rate, haplotype freq(if 1) 1 2 3 4 << order of loci 1 2 << affectation, # alleles [CHED] 9.9900000000E-01 1.0000000000E-03 << gene freqs 1 << number of liability classes 0.000 1.000 1.000 << genotype penetrances 2 4 << binary factors, # alleles [114 ] 6.0000000000E-02 8.1000000000E-01 1.0000000000E-02 1.2000000000E-01 << gene freqs 4 << number of binary factors 1 0 0 0 0 1 0 0 0 0 1 0 0 0 0 1 2 5 << binary factors, # alleles [48 ] 2.5000000000E-01 3.0000000000E-01 1.3000000000E-01 1.9000000000E-01 1.3000000000E-01 << gene freqs 5 << number of binary factors 1 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 1 2 5 << binary factors, # alleles [471 ] 1.7000000000E-01 2.5000000000E-01 1.0000000000E-01 3.0000000000E-01 1.8000000000E-01 << gene freqs 5 << number of binary factors 1 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 1 0 0 << sex difference (if 1) and interference (if 1) 0.0 0.0 0.0 << recombination values 1 << this locus may have iterated values 1 1 1 ----- and pedfile.dat ---- 1 1 0 0 4 0 0 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 1 1 2 0 0 4 0 0 2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 2 1 3 0 0 8 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 3 1 4 1 2 8 6 6 2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 4 1 5 0 0 10 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 5 1 6 1 2 10 0 0 2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 6 1 7 0 0 13 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 7 1 8 3 4 13 0 0 2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 8 1 9 0 0 22 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 9 1 10 5 6 22 12 12 2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 10 1 11 0 0 23 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 11 1 12 5 6 23 0 0 2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 12 1 13 7 8 26 16 16 1 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 13 1 14 0 0 26 0 0 2 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 14 1 15 0 0 27 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 15 1 16 7 8 27 18 18 2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 16 1 17 0 0 33 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 17 1 18 7 8 33 20 20 2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 18 1 19 0 0 36 0 0 1 0 1 1 1 0 0 0 0 1 1 0 0 1 0 1 0 Ped: 1 Per: 19 1 20 7 8 36 0 0 2 0 2 1 0 0 1 0 1 0 0 1 0 1 1 0 0 Ped: 1 Per: 20 1 21 0 0 39 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 21 1 22 9 10 39 0 0 2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 22 1 23 11 12 40 0 0 1 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 23 1 24 0 0 40 0 0 2 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 24 1 25 0 0 42 0 0 1 0 1 0 1 0 1 1 1 0 0 0 0 0 0 1 0 Ped: 1 Per: 25 1 26 13 14 42 0 0 2 0 2 1 0 0 0 0 0 0 0 1 0 1 1 0 0 Ped: 1 Per: 26 1 27 15 16 44 29 29 1 0 2 0 0 1 1 0 1 1 0 0 0 1 0 0 1 Ped: 1 Per: 27 1 28 0 0 44 0 0 2 0 1 0 1 0 0 0 0 0 0 0 0 1 0 1 0 Ped: 1 Per: 28 1 29 15 16 0 31 31 1 0 1 0 0 0 1 0 1 0 1 0 0 0 1 0 1 Ped: 1 Per: 29 1 30 0 0 46 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 30 1 31 15 16 46 0 0 2 0 2 0 0 1 1 0 1 1 0 0 1 1 0 0 0 Ped: 1 Per: 31 1 32 0 0 48 0 0 1 0 1 0 1 0 0 1 1 0 0 0 0 1 0 0 0 Ped: 1 Per: 32 1 33 17 18 48 35 35 2 0 2 1 0 1 0 0 0 0 1 1 1 1 0 0 0 Ped: 1 Per: 33 1 34 0 0 54 0 0 1 0 1 0 1 0 0 1 1 0 0 0 1 0 1 0 0 Ped: 1 Per: 34 1 35 17 18 54 0 0 2 0 2 1 0 1 0 0 0 0 1 1 0 1 0 0 1 Ped: 1 Per: 35 1 36 19 20 0 37 37 2 0 2 1 1 0 0 0 0 0 1 1 0 1 0 0 0 Ped: 1 Per: 36 1 37 19 20 0 0 0 2 0 1 0 1 0 1 0 1 0 1 0 0 1 1 0 0 Ped: 1 Per: 37 1 38 0 0 56 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Ped: 1 Per: 38 1 39 21 22 56 0 0 2 0 2 1 0 0 1 0 1 0 0 1 0 1 0 1 0 Ped: 1 Per: 39 1 40 23 24 0 41 41 1 0 2 1 1 0 0 0 0 0 1 1 0 1 0 1 0 Ped: 1 Per: 40 1 41 23 24 0 0 0 2 0 1 0 1 0 1 0 1 0 1 0 0 1 1 0 0 Ped: 1 Per: 41 1 42 25 26 0 43 43 1 0 1 1 0 0 1 0 1 0 0 1 0 0 1 1 0 Ped: 1 Per: 42 1 43 25 26 0 0 0 2 0 2 1 1 0 0 1 0 0 0 1 0 1 0 1 0 Ped: 1 Per: 43 1 44 27 28 0 45 45 2 0 2 0 1 1 0 1 0 1 0 0 0 1 0 0 0 Ped: 1 Per: 44 1 45 27 28 0 0 0 1 0 1 0 1 0 1 0 1 0 1 0 0 1 0 0 1 Ped: 1 Per: 45 1 46 30 31 0 47 47 1 0 2 0 0 1 1 0 0 1 1 0 0 1 0 0 1 Ped: 1 Per: 46 1 47 30 31 0 0 0 2 0 1 0 1 0 1 1 1 0 0 0 1 0 0 1 0 Ped: 1 Per: 47 1 48 32 33 0 50 50 1 0 1 0 1 1 0 0 1 0 1 0 1 1 0 0 0 Ped: 1 Per: 48 1 49 0 0 59 0 0 1 0 1 0 1 0 0 0 0 1 0 1 0 0 0 1 1 Ped: 1 Per: 49 1 50 32 33 59 51 51 2 0 2 1 1 0 0 1 0 0 0 1 0 1 0 0 0 Ped: 1 Per: 50 1 51 32 33 0 53 53 2 0 2 1 1 0 0 0 1 0 0 1 0 1 0 0 0 Ped: 1 Per: 51 1 52 0 0 62 0 0 1 0 1 0 1 0 0 1 0 0 1 0 0 0 0 1 1 Ped: 1 Per: 52 1 53 32 33 62 0 0 2 0 2 1 1 0 0 1 0 0 0 1 0 1 0 0 0 Ped: 1 Per: 53 1 54 34 35 0 55 55 1 0 1 0 1 1 0 1 0 0 1 0 1 0 0 0 1 Ped: 1 Per: 54 1 55 34 35 0 0 0 2 0 2 1 1 0 0 0 0 0 0 0 1 1 0 0 0 Ped: 1 Per: 55 1 56 38 39 64 58 58 1 0 2 1 0 1 0 0 0 1 0 1 0 1 0 1 0 Ped: 1 Per: 56 1 57 0 0 64 0 0 2 0 1 0 1 0 1 0 1 1 0 0 1 0 0 0 0 Ped: 1 Per: 57 1 58 38 39 0 0 0 2 0 1 0 0 1 1 0 1 1 0 0 0 1 0 0 0 Ped: 1 Per: 58 1 59 49 50 0 60 60 2 0 1 0 1 0 0 1 0 1 0 0 0 1 0 0 1 Ped: 1 Per: 59 1 60 49 50 0 61 61 2 0 1 0 1 0 0 1 0 1 0 0 0 1 0 0 1 Ped: 1 Per: 60 1 61 49 50 0 0 0 1 0 1 0 1 0 0 1 0 1 0 0 0 1 0 0 1 Ped: 1 Per: 61 1 62 52 53 0 63 63 2 0 2 1 1 0 0 0 0 0 1 1 0 0 0 0 0 Ped: 1 Per: 62 1 63 52 53 0 0 0 2 0 1 0 1 0 0 0 0 0 0 0 0 1 0 1 0 Ped: 1 Per: 63 1 64 56 57 0 0 0 2 0 2 1 1 0 0 0 0 1 0 1 1 0 0 1 0 Ped: 1 Per: 64 ----- and the final results, as displayed by lrp: ---- Order 0.0 0.05 0.1 0.15 0.2 ----- ------- ------- ------- ------- ------- 1=4 3.39 5.05 4.66 4.14 3.55 a ----- All suggestions welcome. Frank From owner-gene-linkage@net.bio.net Thu Aug 17 23:00:00 1995 Path: biosci!daresbury!nntp-trd.UNINETT.no!Norway.EU.net!EU.net!news.sprintlink.net!europa.chnt.gtegsc.com!howland.reston.ans.net!tank.news.pipex.net!pipex!sunsite.doc.ic.ac.uk!hgmp.mrc.ac.uk!ifenton From: ifenton@hgmp.mrc.ac.uk (I. Fenton) Newsgroups: bionet.molbio.gene-linkage Subject: Re: MLINK: impossible result? Date: 18 Aug 1995 14:27:45 GMT Organization: UK HGMP Resource Centre Lines: 16 Message-ID: <412811$t4l@mercury.hgmp.mrc.ac.uk> References: <4122p8$q03@mercury.hgmp.mrc.ac.uk> NNTP-Posting-Host: tin.hgmp.mrc.ac.uk Keywords: MLINK, linkage [snip, snip - discussion of possibly weird mlink result] my random thoughts... could the DATAIN.DAT file be posted, so that we can see exactly how the disease and/or liability classes have been set up. there may be something subtle in there that you're not spotting. also a lod-score table and/or PEDIN.DAT may help us. weird thought- could the family be displayed as a picture on the h.g.m.p.'s web-page somewhere ? then we could look at the pedigree without sending a binary to this newsgroup or messing about with f.t.p. sites and the like. just a thought. cheers, Iain Fenton, Cardiff, UK. From owner-gene-linkage@net.bio.net Thu Aug 17 23:00:00 1995 Path: biosci!bcm!news.msfc.nasa.gov!newsfeed.internetmci.com!news.sprintlink.net!in1.uu.net!tank.news.pipex.net!pipex!sunsite.doc.ic.ac.uk!daresbury!not-for-mail From: Lucien Bachner Newsgroups: bionet.molbio.gene-linkage Subject: Re: MLINK: impossible result? Date: 18 Aug 1995 20:41:45 +0100 Lines: 4 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <412qdp$3ek@mserv1.dl.ac.uk> Original-To: fvisser@hgmp.mrc.ac.uk My idea is tthat the program may consider the possibility of a double crossover. As it's 10pm I'm not sure if that hypothesis is correct or not. Lucien Bachner From owner-gene-linkage@net.bio.net Sun Aug 20 23:00:00 1995 Newsgroups: bionet.molbio.gene-linkage Path: biosci!bloom-beacon.mit.edu!newsfeed.internetmci.com!news.sprintlink.net!in2.uu.net!tank.news.pipex.net!pipex!uknet!bcc.ac.uk!news From: dcurtis@hgmp.mrc.ac.uk (David Curtis) Subject: Re: MLINK: impossible result? Message-ID: <1995Aug21.080753.63962@ucl.ac.uk> Date: Mon, 21 Aug 1995 08:04:55 GMT References: <4122p8$q03@mercury.hgmp.mrc.ac.uk> <412811$t4l@mercury.hgmp.mrc.ac.uk> <412a2n$q03@mercury.hgmp.mrc.ac.uk> Organization: University College London X-Newsreader: Forte Free Agent 1.0.82 Lines: 27 >datain.dat: >-------- > 4 0 0 1 << no loci, risk locus, sexlinked(if 1) > 0 0.0 0.0 0 << mut locus, mut rate, haplotype freq(if 1) > 1 2 3 4 << order of loci > > 1 2 << affectation, # alleles [CHED] > 9.9900000000E-01 1.0000000000E-03 << gene freqs > 1 << number of liability classes > 0.000 1.000 1.000 << genotype penetrances > Because the disease allele has a frequency of 0.001, there is a small though not infinitesimal probability for there to be two different disease alleles entering the pedigree, one segregating in one branch and another segregating in the other branch. Thus your results are just what I would expect. I would predict that as you decrease the frequency of the disease allele, so the lod score at zero will decrease, eventually approaching minus infinity as the allele frequency becomes vanishingly small. I would also predict that the lod score at small non-zero values for theta will change very little when you do this, for reasons which I hope are obvious. From owner-gene-linkage@net.bio.net Mon Aug 21 23:00:00 1995 Path: biosci!daresbury!hgmp.mrc.ac.uk!news From: jattwood@hgmp.mrc.ac.uk (Mr J. Attwood) Newsgroups: bionet.molbio.gene-linkage Subject: Re: MLINK: impossible result? Date: 22 Aug 1995 12:16:56 GMT Organization: UK HGMP Resource Centre Lines: 26 Message-ID: <41chro$n9q@mercury.hgmp.mrc.ac.uk> References: <1995Aug21.080753.63962@ucl.ac.uk> Reply-To: jattwood@hgmp.mrc.ac.uk NNTP-Posting-Host: iron.hgmp.mrc.ac.uk In article 63962@ucl.ac.uk, dcurtis@hgmp.mrc.ac.uk (David Curtis) writes: > Because the disease allele has a frequency of 0.001, there is a small > though not infinitesimal probability for there to be two different > disease alleles entering the pedigree, one segregating in one branch > and another segregating in the other branch. Thus your results are > just what I would expect. Yes, I agree with Dave. You could try giving individual #2 a normal parent, in order to see whether you do, then, get -infinity at a theta of zero. This will tell you whether the program is considering the possibility that a founder was homozygous for the disease allele. I haven't drawn out the pedigree, but I suspect that this is the most likely case, as you don't have anyone whose disease status is unkown and therefore it is not possible for two unrelated members to be independently bringing a disease allele into different branches of the pedigree. I think that it is a general rule that, when the Linkage package comes up with surprising results, there is usually a second possibility which it is taking into account and whose lodscore curve is modifying the expected one. The strength of the Linkage package is its ability to fill in for missing data, and it often allows for things, like this, not immediately obvious to humans. John Attwood. From owner-gene-linkage@net.bio.net Tue Aug 22 23:00:00 1995 Path: biosci!daresbury!nntp-trd.UNINETT.no!Norway.EU.net!EU.net!news2.EUnet.fr!ceph.cephb.fr!linehan From: linehan@ceph.cephb.fr (Paul Linehan) Newsgroups: bionet.molbio.gene-linkage Subject: Microsat Associations Date: 23 Aug 1995 18:54:40 +0200 Organization: Fondation J. Dausset - CEPH Lines: 29 Distribution: world Message-ID: <41fmgg$41n@ceph.cephb.fr> NNTP-Posting-Host: ceph.cephb.fr I have been impressed by the quality of advice given in this group. I would appreciate help. When one is performing a study of association of alleles with a particular trait, is there any point in studying microsatellites and frequencies of different microsat alleles which may have an association with the trait. I thought that microsats would evolve too quickly to be of use, but I'm open to contradiction. References particularly welcome. Thanks. Paul... From owner-gene-linkage@net.bio.net Wed Aug 23 23:00:00 1995 Newsgroups: bionet.molbio.gene-linkage Path: biosci!daresbury!nntp-trd.UNINETT.no!sunic!sunic.sunet.se!seunet!news2.swip.net!weld.news.pipex.net!pipex!tank.news.pipex.net!pipex!uknet!bcc.ac.uk!news From: dcurtis@hgmp.mrc.ac.uk (David Curtis) Subject: Re: Linkage in DZ twins Message-ID: <1995Aug24.150451.55519@ucl.ac.uk> Date: Thu, 24 Aug 1995 15:01:40 GMT References: <41i03b$ngs@mercury.hgmp.mrc.ac.uk> Organization: University College London X-Newsreader: Forte Free Agent 1.0.82 Lines: 20 r.keen@umds.ac.uk wrote: >I am interested in doing linkage in DZ twins, using them as age- >matched sibs. Is anyone aware if the power of such anaysis would >be similar to normal sibs, with particular reference to late-onset >and age-related diseases. I should value opinions and any refernces. For quantitative traits the age-matching will be an advantage. For rare-ish disorders you'll probably get most power with pairs of affected sibs rather than discordant sibs, so collecting affected sib pairs might be better than collecting twins with only one guaranteed affected. Pak Sham is about to embark on a big study of dizygotic twins so you could email him: p.sham@ucl.ac.uk Dave Curtis (dcurtis@hgmp.mrc.ac.uk) Institute of Psychiatry, London http://www.iop.bpmf.ac.uk/home/depts/psychmed/general/dcurtis/dcurtis.htm From owner-gene-linkage@net.bio.net Wed Aug 23 23:00:00 1995 Newsgroups: bionet.molbio.gene-linkage Path: biosci!daresbury!nntp-trd.UNINETT.no!sunic!sunic.sunet.se!mn6.swip.net!seunet!news2.swip.net!plug.news.pipex.net!pipex!tank.news.pipex.net!pipex!uknet!bcc.ac.uk!news From: dcurtis@hgmp.mrc.ac.uk (David Curtis) Subject: Re: Microsat Associations Message-ID: <1995Aug24.074115.53840@ucl.ac.uk> Date: Thu, 24 Aug 1995 07:38:07 GMT References: <41fmgg$41n@ceph.cephb.fr> Organization: University College London X-Newsreader: Forte Free Agent 1.0.82 Lines: 39 linehan@ceph.cephb.fr (Paul Linehan) wrote: > When one is performing a study of association of alleles with a >particular trait, is there any point in studying microsatellites and frequencies >of different microsat alleles which may have an association with the trait. Yes certainly. >I thought that microsats would evolve too quickly to be of use, but I'm open >to contradiction. References particularly welcome. I think two studies in Nature Genetics recently have reported linkage disequilibrium between diabetes and microsatellites. Other disorders also demonstrate this phenomenon. They do seem to be conserved over time, and we described linkage disequilibrium between two different microsatellite polymorphisms: Sherrington R, Melmer G, Dixon M, Curtis D, Mankoo B, Kalsi G, Gurling HMD. Linkage disequilibrium between two highly polymorphic microsatellites. American Journal of Human Genetics 1991 49: 966-971. Analysing polymorphisms with large numbers of alleles can present difficulties. Joe Terwilliger recently described a method in Am J Hum Genet, and we have described other methods for use in association and transmission disequilibrium studies respectively: Sham PC, Curtis D. Monte Carlo tests for associations between disease and alleles at highly polymorphic loci. Ann Hum Genet 1995 59: 97-105. Sham PC, Curtis D. An extended transmission/disequilibrium test (TDT) for multi-allele marker loci. Ann Hum Genet 1995: 323-336. Dave Curtis (dcurtis@hgmp.mrc.ac.uk) Institute of Psychiatry, London http://www.iop.bpmf.ac.uk/home/depts/psychmed/general/dcurtis/dcurtis.htm From owner-gene-linkage@net.bio.net Wed Aug 23 23:00:00 1995 Path: biosci!daresbury!nntp-trd.UNINETT.no!Norway.EU.net!EU.net!news.sprintlink.net!in1.uu.net!news1.digital.com!decwrl!waikato!canterbury.ac.nz!usenet From: jeffric@kea.lincoln.ac.nz Newsgroups: bionet.cellbiol,bionet.general,bionet.genome.chromosones,bionet.microbiology,bionet.molbio.gene-linkage,bionet.molbio.yeast,sci.bio.microbiology,sci.med.immunology,sci.research Subject: I am looking for a mutant ecoli... Date: Thu, 24 Aug 1995 00:42:32 GMT Organization: Universities of Canterbury and Lincoln Lines: 27 Sender: m.perkins@student.canterbury.ac.nz Distribution: world Message-ID: <41gleo$471@cantua.canterbury.ac.nz> Reply-To: jeffric@kea.lincoln.ac.nz NNTP-Posting-Host: misc1695.tacacs.canterbury.ac.nz Summary: Request for help with a mutant ecoli strain Keywords: ecoli, bacteria, research, help, mutant, lactose, lac operon, X-Newsreader: Forte Free Agent 1.0.82 Xref: biosci bionet.cellbiol:2784 bionet.general:16630 bionet.microbiology:3054 bionet.molbio.gene-linkage:823 bionet.molbio.yeast:3582 sci.bio.microbiology:1378 sci.med.immunology:2139 sci.research:6688 *Wanted* (cross-posted) *Needed* An E.coli that has a high expression of the lac operon specifically high expression of the lac-permease and b-galactosidase proteins), and hence has unrestricted growth on lactose. However (and heres the cruncher) the strain must also have mutations in its pts carbohydrate system (specifically HPro and enz1) so it cannot utilise pts carbohydrates to any great extent compared to lactose and must also have mutations in its galactose permease system so it cannot readily use galactose as a carbohydrate source. That is does a strain exist that can preferentially use lactose over other common carbohydrates as a primary energy source? Where is this strain? (Sorry for the cross-post; a (polite) recommendation about appropriate groups would be appreciated.) Please reply by *mail* to jeffric@kea.lincoln.ac.nz THANKYOUTHANKYOUTHANKYOUTHANKHELLOYOUTHANKYOUTHSNKYOU From owner-gene-linkage@net.bio.net Wed Aug 23 23:00:00 1995 Path: biosci!daresbury!hgmp.mrc.ac.uk!rkeen From: r.keen@umds.ac.uk Newsgroups: bionet.molbio.gene-linkage Subject: Linkage in DZ twins Date: 24 Aug 1995 13:50:35 GMT Organization: MRC Human Genome Resource Centre Lines: 11 Message-ID: <41i03b$ngs@mercury.hgmp.mrc.ac.uk> NNTP-Posting-Host: iron.hgmp.mrc.ac.uk Originator: rkeen@iron I am interested in doing linkage in DZ twins, using them as age- matched sibs. Is anyone aware if the power of such anaysis would be similar to normal sibs, with particular reference to late-onset and age-related diseases. I should value opinions and any refernces. Richard Keen Molecular Immunogenetics UMDS London UK From owner-gene-linkage@net.bio.net Wed Aug 23 23:00:00 1995 Path: biosci!rutgers!gatech!newsfeed.internetmci.com!news.sprintlink.net!news.oz.net!news.alt.net!news.u.washington.edu!max1.u.washington.edu!wijsman From: wijsman@max1.u.washington.edu Newsgroups: bionet.molbio.gene-linkage Subject: Re: Microsat Associations Date: 24 Aug 95 09:22:28 PST Organization: University of Washington, Seattle WA Lines: 38 Distribution: world Message-ID: <1995Aug24.092228.1@max1.u.washington.edu> NNTP-Posting-Host: max1.u.washington.edu > When one is performing a study of association of alleles with a > particular trait, is there any point in studying microsatellites and frequencies > of different microsat alleles which may have an association with the trait. > I am assuming that in such an association study you are dealing with the situation where you have mapped a disease gene to a particular chromsomal region, and you are looking for an association which may suggest that such a marker is very close to the gene. In such a case the empirical data says that yes, it is very useful to look for associations between such markers and the disease locus. We reported such an association with Werner's syndrome (AJHG 1994, 55:356-364), and a quick medline search with keywords "linkage disequilibrium" and "microsatellite" pulls up about 60 such references since 1990, most of which (although not all) report or use linkage disequilibrium with microsatellites. > > I thought that microsats would evolve too quickly to be of use, but I'm open > to contradiction. References particularly welcome. > The mutation rate does add some noise to the data which complicates analysis of extended haplotypes, but the rate is not so high that such associations cannot be seen. In fact, for markers with many alleles, because the "average" disease mutation ends up on a haplotype with an allele which is not too high in frequency, the subsequent enrichment of that allele in the case population is particularly easy to detect. It is, however, important to use a method of analysis which can both cope with small cell sizes and which does not require the "pooling" of alleles. We have results which indicate that pooling of alleles (so that you can perform a chi square test) can give very misleading results, either way - false positive or false negative. Fisher exact works when there aren't too many alleles at the marker (it is computationally intensive, however). The Monte Carlo Markov chain method of Guo & Thompson (Biometrics, June 1992) works very well for larger numbers of alleles, and is computationally much faster. Ellen Wijsman wijsman@u.washington.edu From owner-gene-linkage@net.bio.net Thu Aug 24 23:00:00 1995 Path: biosci!rutgers!uwm.edu!vixen.cso.uiuc.edu!howland.reston.ans.net!news.sprintlink.net!news.monad.net!usenet From: Ron Roy Newsgroups: bionet.molbio.gene-linkage Subject: Re: Microsat Associations Date: 25 Aug 1995 13:02:56 GMT Organization: MonadNet Lines: 30 Message-ID: <41khm0$98a@top.monad.net> References: <41fmgg$41n@ceph.cephb.fr> NNTP-Posting-Host: mikemethe.top.monad.net > > > > I have been impressed by the quality of advice given in this group. > > > I would appreciate help. > > > > When one is performing a study of association of alleles with a > particular trait, is there any point in studying microsatellites and frequencies > of different microsat alleles which may have an association with the trait. > > > I thought that microsats would evolve too quickly to be of use, but I'm open > to contradiction. References particularly welcome. > > > Thanks. > > > > Paul... > > > > > From owner-gene-linkage@net.bio.net Thu Aug 24 23:00:00 1995 Path: biosci!agate!howland.reston.ans.net!swrinde!tank.news.pipex.net!pipex!in2.uu.net!EU.net!Belgium.EU.net!chaos.kulnet.kuleuven.ac.be!usenet From: Chris Michiels Newsgroups: bionet.cellbiol,bionet.general,bionet.genome.chromosones,bionet.microbiology,bionet.molbio.gene-linkage,bionet.molbio.yeast,sci.bio.microbiology,sci.med.immunology,sci.research Subject: Re: I am looking for a mutant ecoli... Date: 25 Aug 1995 07:37:31 GMT Organization: KULeuven Lines: 10 Message-ID: <41jujr$qqo@chaos.kulnet.kuleuven.ac.be> References: <41gleo$471@cantua.canterbury.ac.nz> NNTP-Posting-Host: dip26.agr.kuleuven.ac.be Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 1.1N (Windows; I; 16bit) Xref: biosci bionet.cellbiol:2795 bionet.general:16655 bionet.microbiology:3068 bionet.molbio.gene-linkage:828 bionet.molbio.yeast:3599 sci.bio.microbiology:1392 sci.med.immunology:2150 sci.research:6713 Have you checked out the E. coli Genetic Stock Center: a large collection of E. coli strains and mutants at Yale University? You can search the collection on line at: http://cgsc.biology.yale.edu Chris Michiels Lab. Food Microbiology KULeuven Heverlee (Belgium) From owner-gene-linkage@net.bio.net Tue Aug 29 23:00:00 1995 Path: biosci!rutgers!uwm.edu!news.moneng.mei.com!bloom-beacon.mit.edu!gatech!newsfeed.internetmci.com!info.ucla.edu!library.ucla.edu!nntp.club.cc.cmu.edu!clpgh.org!kaplanr From: kaplanr@clpgh.org (Richard Kaplan) Newsgroups: bionet.molbio.gene-linkage Subject: Microcephaly Message-ID: <1995Aug29.102312.4017@clp2> Date: 29 Aug 95 10:23:12 -5 Organization: Carnegie Library of Pittsburgh Lines: 13 Hello, I am posting this in an attempt to find some preliminary information, and begin to track some ideas. I have a two year old son with microcephaly, %60-70 global developmental delays, no medical problems (he's not fragile), and no diagnosis or cause. He has been tested for Fragile-X Syndrome, and the ususal bllod tests, a chromosomal workup, MRI, etc. Do you know of anyone doing work in Microcephaly, above and beyond its link to Down Syndrome? Any help or direction would be greatly appreciated. Richard Kaplan kaplanr@clpgh.org From owner-gene-linkage@net.bio.net Wed Aug 30 23:00:00 1995 Path: biosci!bcm.tmc.edu!news.msfc.nasa.gov!newsfeed.internetmci.com!usenet.eel.ufl.edu!gatech!newsfeed.pitt.edu!uunet!in1.uu.net!news.sprintlink.net!in2.uu.net!spcuna!news.columbia.edu!merhaba.cc.columbia.edu!wl101 From: wl101@merhaba.cc.columbia.edu (Wentian Li) Newsgroups: bionet.molbio.gene-linkage Subject: LCP on solaris Date: 31 Aug 1995 16:48:29 GMT Organization: Columbia University Lines: 19 Message-ID: <424p4t$bmh@apakabar.cc.columbia.edu> NNTP-Posting-Host: merhaba.cc.columbia.edu i'm wondering whether anybody has compiled LCP (linkage control program) on SUN's Solaris? we don't have a Solaris machine to do a test, but several people who downloaded the LCP source code from our FTP site to their Solaris machine have difficulty in installing it. if you have an experience, we would be very interested to know. your information will help many other people! wentian li statistical genetics group columbia university email:wl101@columbia.edu, wli@linkage.cpmc.columbia.edu web: http://linkage.cpmc.columbia.edu/wli/ From owner-gene-linkage@net.bio.net Thu Aug 31 23:00:00 1995 Path: biosci!bcm.tmc.edu!news.msfc.nasa.gov!newsfeed.internetmci.com!tank.news.pipex.net!pipex!in1.uu.net!cis.ohio-state.edu!magnus.acs.ohio-state.edu!lerc.nasa.gov!purdue!oitnews.harvard.edu!news.sesqui.net!rice!cs.rice.edu!schaffer From: schaffer@cs.rice.edu (Alex Schaffer) Newsgroups: bionet.molbio.gene-linkage Subject: Re: LCP for Solaris Date: 1 Sep 1995 20:23:03 GMT Organization: Rice University Lines: 21 Message-ID: <427q37$6e0@larry.rice.edu> NNTP-Posting-Host: cs.rice.edu In a previous post to bionet.molbio.gene-linkage, Wentian Li (wl101@merhaba.cc.columbia.edu), inquired about the existence of an LCP executable for Solaris. I encountered this problem several weeks ago, and subsequently several FASTLINK users have complained about several of the other LINKAGE auxiliary programs for Solaris. Luckily, there are adventuresome FASTLINK users who worry about these things before I do. In this particular case, both Carolyn Bucholtz in Sydney (bucholtz@angis.su.OZ.au) and Gyorgy Simon in Milan (simon@andromeda.hsr.it) offered suitable Solaris executables for all the LINKAGE auxiliary programs. Carolyn's offer came first, so I have been using the binaries Carolyn prepared. They work fine. Thanks Carolyn! Alejandro Schaffer schaffer@nchgr.nih.gov