From owner-gene-linkage@net.bio.net Wed Nov 02 22:00:00 1994 Path: biosci!daresbury!bioftp.unibas.ch!citi2.fr!jussieu.fr!cea.fr!usenet From: cisitm@albert.cad.cea.fr (Pierre Didierjean) Newsgroups: bionet.molbio.gene-linkage Subject: *** Q: WHAT KIND OF PEOPLE ON THE NET ? Date: 3 Nov 1994 16:17:08 GMT Organization: SSII Lines: 28 Sender: cisitm@albert.cad.cea.fr Message-ID: <39b2e4$9pi@anemone.saclay.cea.fr> NNTP-Posting-Host: nyassa.cad.cea.fr I'd like to know what kind of people i find on the net. Students, Commercials, Adminitrations, Scientifics or what ?? Is anybody knows that or have statistical results ? What are YOU doing in life ? I am a system administrator. Thanks for the answers and sorry for my english ..... Bye +-----------------------------------------------------------------------------+ | Pierre DIDIERJEAN | | | | Administrateur Systeme UNIX | | Cisi, Aix-en-Provence | | France | +-----------------------------------------------------------------------------+ | email : cisitm@albert.cad.cea.fr | +-----------------------------------------------------------------------------+ From owner-gene-linkage@net.bio.net Tue Nov 08 22:00:00 1994 Path: biosci!CORONA.MED.UTAH.EDU!dnielsen From: dnielsen@CORONA.MED.UTAH.EDU (Dahlia Nielsen) Newsgroups: bionet.molbio.gene-linkage Subject: MAPMAKER/QTL question Date: 9 Nov 1994 15:07:48 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 10 Sender: daemon@net.bio.net Distribution: world Message-ID: <199411092302.QAA00633@corona.med.utah.edu> NNTP-Posting-Host: net.bio.net To: Users of MAPMAKER/QTL Re: Lod scores for QTL location data I'm interested in getting a lod score or some other likelihood ratio value for a QTL analyzed at a given map position within MAPMAKER/QTL. In the output produced by default, there is a value printed for log-likelihood, which appears to be the likelihood of the data at the location specified under computed MLE values. Is there a way to print out the likelihood of the data at the same location under the null hypothesis that there is no QTL at this location? From owner-gene-linkage@net.bio.net Wed Nov 09 22:00:00 1994 Path: biosci!bloom-beacon.mit.edu!spool.mu.edu!howland.reston.ans.net!pipex!uunet!Germany.EU.net!netmbx.de!zrz.TU-Berlin.DE!cs.tu-berlin.de!kaikuh From: kaikuh@cs.tu-berlin.de (Kai) Newsgroups: bionet.molbio.gene-linkage Subject: Genetic Engineering Date: 10 Nov 1994 11:18:27 GMT Organization: Technical University of Berlin, Germany Lines: 26 Message-ID: <39svi3$ehn@news.cs.tu-berlin.de> NNTP-Posting-Host: manelaq.cs.tu-berlin.de Mime-Version: 1.0 Content-Type: text/plain; charset=iso-8859-1 Content-Transfer-Encoding: 8bit Summary: Genetic Engineering Keywords: Genetic Engineering Hello out there, ================ I don't know if this is the right group to post but I have the following problem: a friend of mine will have to read a report on genetic engineering in a few weeks. Unfortunately she does not have access to the Internet; thus she asked me to post some questions here because she has to mention something about the United States. She would like to know something of the party platform both of the democrats and of the republicans, concerning genetic engineering and its laws in the USA. Furthermore she would appreciate it to get some statements of the economy/ business/trade and industry. It would be great if anyone was able to send me some articles, drafts etc. or just some information where we can find something like that (e-mail preferred). Thank you very much in advance, Kai -- ,,, (o o) -------------------------------oOO--(_)--OOo----------------------------- Make it as easy as possible, but not easier! kaikuh@cs.tu-berlin.de From owner-gene-linkage@net.bio.net Thu Nov 10 22:00:00 1994 Path: biosci!bloom-beacon.mit.edu!gatech!howland.reston.ans.net!pipex!oleane!jussieu.fr!univ-lyon1.fr!swidir.switch.ch!scsing.switch.ch!aragorn.unibe.ch!itz_baeumle.unibe.ch!baeumle From: baeumle@itz.unibe.ch (Etienne Baeumle) Newsgroups: bionet.molbio.gene-linkage Subject: Installation of Linkage on Alpha-Systems Date: Fri, 11 Nov 1994 08:33:26 GMT Organization: University of Bern, Switzerland Lines: 25 Message-ID: NNTP-Posting-Host: itz_baeumle.unibe.ch X-Newsreader: Trumpet for Windows [Version 1.0 Rev A] Hello, I would like to install linkage 5.1 and fastlink on OpenVMS AXP V6.1 and/or on OSF/1. So I downloaded the versions from the requiered ftp sites (problems with corona, saying that user anonymous is unknown...). For the linkage packet there is a version for VMS and a version for Sun. I tried to install the VMS version on OpenVMS AXP but had problems with the UIP part of the packet, especially with LCP and LLB, e.g. with a routine called getc.mar (in: uip.lcp.src, seems to be a routine written in assembler for VMS and not running under VMS AXP). So I tried to install the Sun version on OSF/1, but had similar problems. Please, is there anyone out there having installed the UIP part successfully on OpenVMS AXP or on OSF/1 (DEC Alpha) and could give me a hint? It would be great. The fastlink version runs under OSF/1 without a problem but it would be nice to use the LINKAGE auxiliary programs (lcp, lrp, preplink etc.) too. Thank you very much in advance, Etienne. From owner-gene-linkage@net.bio.net Thu Nov 10 22:00:00 1994 Path: biosci!agate!howland.reston.ans.net!pipex!sunsite.doc.ic.ac.uk!hgmp.mrc.ac.uk!ifenton From: ifenton@crc.ac.uk (I. Fenton) Newsgroups: bionet.molbio.gene-linkage Subject: bizarre LINKAGE results - bug ? Date: 11 Nov 1994 13:59:39 GMT Organization: MRC Human Genome Resource Centre Lines: 33 Message-ID: <39vtcb$gg@mercury.hgmp.mrc.ac.uk> NNTP-Posting-Host: tin.hgmp.mrc.ac.uk hello fellow-linkage people, ok, here's the deal. i've got a PEDIN.DAT file with a few families in them, and my DATAIN.DAT file, i run a simple 2-point MLINK run on them on my pc, and all is lovely except that MLINK gives the last family a -infinity lod score at 5%,10%,20%,30%,40% recombination values, *BUT* gives a proper likelihood (lod score = -0.7 or something) at 0% and 1% distance. what gives ?!? i've seen -infinity across the board before (usually i've cocked-up something in DATAIN.DAT) but never seen the likelihoods fail at 5% or more, but work at 0% and 1% !?! i am using the dos version of linkage, pulled of jurg ott's ftp-site a few months ago. note - i ran it on a sparc-station here, and sun-linkage gave me proper likelihoods, and UNKNOWN is always happy so i don't think there is anything wrong with the compatibility of the genotype data. i think it's a bug (shock ! horror !) or simply am i missing something obvious ? the files are a bit big, so i won't post them to the newsgroup unless asked, but for reference MLINK is compiled for 14 alleles (i don't like recoding !) although there are only 9 alleles in this large (and largely untyped) family, but all the other families in the PEDIN.DAT file go ok. also why does the sparcstation version of linkage give a different result to the pc-version ??! *ANY* comments/suggestions are welcomed..., esp. from jurg or any of the other "official" LINKAGE shops... thanks, Iain Fenton, Cardiff, UK. From owner-gene-linkage@net.bio.net Thu Nov 10 22:00:00 1994 Path: biosci!news.Stanford.EDU!rutgers!mcrcr6!deustp01 From: deustp01@mcrcr6.med.nyu.edu (Peter D'Eustachio) Newsgroups: bionet.molbio.gene-linkage Subject: Re: Installation of Linkage on Alpha-Systems Message-ID: <1994Nov11.095242.7536@mcrcr6> Date: 11 Nov 94 09:52:42 EDT References: Organization: NYU Medical Center, New York, NY 10016, USA Lines: 17 In article , baeumle@itz.unibe.ch (Etienne Baeumle) writes: > Hello, > > I would like to install linkage 5.1 and fastlink on OpenVMS AXP V6.1 and/or on > OSF/1. So I downloaded the versions from the required ftp sites (problems > with corona, saying that user anonymous is unknown...). Same problem here. So where did you get these programs? > Please, is there anyone out there having installed the UIP part successfully > on OpenVMS AXP or on OSF/1 (DEC Alpha) and could give me a hint? It would be > great. > > The fastlink version runs under OSF/1 without a problem but it would be nice > to use the LINKAGE auxiliary programs (lcp, lrp, preplink etc.) too. Yes, it would be. Could replies go to the newsgroup, please? From owner-gene-linkage@net.bio.net Sun Nov 13 22:00:00 1994 Path: biosci!hgmp.mrc.ac.uk!aking From: aking@hgmp.mrc.ac.uk (Mr. A.W. King) Newsgroups: bionet.molbio.gene-linkage Subject: Re: CHELSEA database Date: 14 Nov 1994 09:51:28 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 3 Sender: daemon@net.bio.net Distribution: world Message-ID: <4901.9411141751@tin.hgmp.mrc.ac.uk> NNTP-Posting-Host: net.bio.net Thanks all, I should have guessed, knew of the CHLC but didn't connect :( Andrew From owner-gene-linkage@net.bio.net Sun Nov 13 22:00:00 1994 Path: biosci!DRUID.HSC.COLORADO.EDU!clancy From: clancy@DRUID.HSC.COLORADO.EDU (Kevin Clancy PhD) Newsgroups: bionet.molbio.gene-linkage Subject: Re: CHELSEA database Date: 14 Nov 1994 08:45:22 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 24 Sender: daemon@net.bio.net Distribution: world Message-ID: References: <3a7msg$5cv@mercury.hgmp.mrc.ac.uk> NNTP-Posting-Host: net.bio.net Dear Andrew, You can find CHLC at the following URL: http://www.chlc.org/ Yours sincerely, Kevin Clancy The Eleanor Roosevelt Institute for Cancer Research 1899 Gaylord St., Denver CO 80206 On 14 Nov 1994, Mr. A.W. King wrote: > > Does anyone have any details on the "CHELSEA" database in the USA. I've not > heard of it here in the UK but the boss was at a meeting where it seems that > it is in common use. > > > Thanks > Andrew > > > From owner-gene-linkage@net.bio.net Sun Nov 13 22:00:00 1994 Path: biosci!bloom-beacon.mit.edu!gatech!swrinde!pipex!sunsite.doc.ic.ac.uk!hgmp.mrc.ac.uk!aking From: aking@hgmp.mrc.ac.uk (Mr. A.W. King) Newsgroups: bionet.molbio.gene-linkage Subject: CHELSEA database Date: 14 Nov 1994 12:57:52 GMT Organization: UK HGMP Resource Centre Lines: 9 Message-ID: <3a7msg$5cv@mercury.hgmp.mrc.ac.uk> NNTP-Posting-Host: tin.hgmp.mrc.ac.uk Does anyone have any details on the "CHELSEA" database in the USA. I've not heard of it here in the UK but the boss was at a meeting where it seems that it is in common use. Thanks Andrew From owner-gene-linkage@net.bio.net Sun Nov 13 22:00:00 1994 Path: biosci!bloom-beacon.mit.edu!gatech!swrinde!pipex!sunsite.doc.ic.ac.uk!hgmp.mrc.ac.uk!gwilliam From: gwilliam@hgmp.mrc.ac.uk (Gary Williams x3294) Newsgroups: bionet.molbio.gene-linkage Subject: Re: CHELSEA database Date: 14 Nov 1994 17:29:38 GMT Organization: UK HGMP Resource Centre Lines: 73 Message-ID: <3a86q2$djs@mercury.hgmp.mrc.ac.uk> References: <3a7msg$5cv@mercury.hgmp.mrc.ac.uk> NNTP-Posting-Host: gallium.hgmp.mrc.ac.uk In article <3a7msg$5cv@mercury.hgmp.mrc.ac.uk>, Mr. A.W. King wrote: > >Does anyone have any details on the "CHELSEA" database in the USA. I've not >heard of it here in the UK but the boss was at a meeting where it seems that >it is in common use. > > >Thanks >Andrew > Andrew, Point your WWW (World Wide Web) browser at the address http://www.chlc.org/ and you will be at the home page of the Cooperative Human Linkage Center. (CHLC) Pronounced 'chelsea' :-) Since you aer a user of the UK MRC HGMP Resource Centre, you can use the WWW browsers in our menu, then look at the 'Genome Centres' link. You will see something like this: ------------------------------------------------------------------------ Welcome to the Cooperative Human Linkage Center World Wide Web server. The following information is available: About the CHLC Project The goal of the Cooperative Human Linkage Center is to develop statistically rigorous, high heterozygosity genetic maps of the human genome that are greatly enriched for the presence of easy-to-use PCR-formatted microsatellite markers. CHLC Maps and Data Access to the information about CHLC generated Markers, genotype collections, CHLC generated framework, skeletal, and scaffold genetic maps of each human chromosome via our WWW server. Science Maps and Data Access to the information on Markers, genotype collections, and Recombination Minimization maps of each human chromosome via our WWW server, as in Science, Volume 265, Page 2049-2054, September 30, 1994 CHLC Marker Search Search by marker name for information available on CHLC markers, map location, primer and pcr conditions, and sequence templates. Copies of the CHLC Newsletter The CHLC newsletter is published semi-annually, and is available in hypertext, text, and postscript versions. Description of terms used in CHLC documents ------------------------------------------------------------------------ Gary Williams Computing Services Section, Email: G.Williams@hgmp.mrc.ac.uk MRC Human Genome Mapping Project Resource Centre, Tel: 01223 494522 Hinxton Hall, Hinxton, Cambridge, CB10 1RQ, UK UK MRC HGMP Resource Centre -- GARY WILLIAMS, Internet: G.Williams@HGMP.MRC.AC.UK Tel: 01223 494522 Computing Services, HGMP Resource Centre, Hinxton Hall, Hinxton, Cambridge, CB10 1RQ UK MRC HGMP Resource Centre From owner-gene-linkage@net.bio.net Sun Nov 13 22:00:00 1994 Path: biosci!daresbury!hgmp.mrc.ac.uk!ifenton From: ifenton@hgmp.mrc.ac.uk (I. Fenton) Newsgroups: bionet.molbio.gene-linkage Subject: ilink allele freq est Date: 14 Nov 1994 19:38:00 GMT Organization: MRC Human Genome Resource Centre Lines: 18 Message-ID: <3a8eao$h54@mercury.hgmp.mrc.ac.uk> NNTP-Posting-Host: tin.hgmp.mrc.ac.uk hello boys + girls, i am using ILINK to estimate some allele frequencies for some markers, and for one run it stopped after 1 iteration saying something like "excessive gradient something" and giving up on any more calculations. sooooooo, what have i done wrong now ? as far as i know that PEDIN.DAT is fine, no locus incompatibility stuff, well UNKNOWN likes it anyway, so what gives ? i am quite willing to accept that i probably haven't put another sodding "1" or "0" or "2" or something in the DATAIN.DAT file. ho hum. for the record, this is the pc-version 5.2 of LINKAGE, and i have ILINK compiled to double-precision, other constants are fairly reasonable 14 alleles per locus, other stuff normal. any comments/suggestions/flames gratefully accepted. Iain Fenton, Cardiff, UK. From owner-gene-linkage@net.bio.net Sun Nov 13 22:00:00 1994 Path: biosci!bloom-beacon.mit.edu!gatech!howland.reston.ans.net!vixen.cso.uiuc.edu!uwm.edu!fnnews.fnal.gov!overload.lbl.gov!dog.ee.lbl.gov!news.cs.utah.edu!news.cc.utah.edu!news.cc.utah.edu!rob From: rob@fosters.med.utah.edu (Rob Sargent) Newsgroups: bionet.molbio.gene-linkage Subject: Re: Installation of Linkage on Alpha-Systems Date: 14 Nov 1994 16:39:52 GMT Organization: University of Utah Lines: 18 Message-ID: References: NNTP-Posting-Host: fosters.med.utah.edu In-reply-to: baeumle@itz.unibe.ch's message of Fri, 11 Nov 1994 08:33:26 GMT I would like to install linkage 5.1 and fastlink on OpenVMS AXP V6.1 and/or on OSF/1. So I downloaded the versions from the requiered ftp sites (problems with corona, saying that user anonymous is unknown...). That ftp server, corona.med.utah.edu, was violoated by some nasty pirate. As a result the sys. admin. yanked the anonymous ftp service. Things have been so harried around here a replacement server has not been implemented. rjs -- Rob Sargent s-mail: Dept. of Human Genetics e-mail: rob@fosters.med.utah.edu U. of Utah Medical School phone: (801) 585-3388 Eccles Genetics Bldg phax : -3833 Salt Lake City, Utah 84112 From owner-gene-linkage@net.bio.net Tue Nov 15 22:00:00 1994 Path: biosci!agate!spool.mu.edu!howland.reston.ans.net!pipex!lyra.csx.cam.ac.uk!sunsite.doc.ic.ac.uk!hgmp.mrc.ac.uk!ifenton From: ifenton@hgmp.mrc.ac.uk (I. Fenton) Newsgroups: bionet.molbio.gene-linkage Subject: mlink don't like me, ilink don't like me... Date: 16 Nov 1994 10:28:05 GMT Organization: MRC Human Genome Resource Centre Lines: 45 Message-ID: <3acmrl$ej5@mercury.hgmp.mrc.ac.uk> NNTP-Posting-Host: tin.hgmp.mrc.ac.uk *shrug* i thought i was used to LINKAGE, but... (1) i posted a note to this group a few days ago [thanks to those who responded] about bizarre MLINK results, namely "-infinity" results in some families. well, now i get some more bizarre results, but ones that aren't as obvious to spot... take this example of a disease v. marker 2-pt MLINK lod score :- theta lod 0% 0.003 1% 0.002 5% -3.079 10% -3.045 20% -2.something etc etc (i am making the figures up from memory, so don't quote me, but they are roughly what happened) soooooo, what gives ? is this just a variation on the problem i posted about a coupla days ago, or not ? also is there any valid reason for this sort of lod-score curve. i don't think so. this is beginnging to get annoying. -infinities (grammer?!) are easy to spot, but if i'm doing a 350-marker genome scan, as i am, i could easily miss this sort of crap. oh dear, woe is me. (2) ILINK. this is fun. i am using ILINK to try and estimate allele frequencies for loads of markers. i know that i am using a 14-allele system, so i code my DATAIN.DAT file for 14 alleles at 1/14 equal starting values. i tell ILINK to do the sums, but is stops after 1 iteration, and gives up. i see that my PEDIN.DAT file has no allele 14. i play about, and find that if i do not have a "n" allele in my PEDIN.DAT file, then ILINK stops, but if i change one person from a 2-12 to a 2-14, then ILINK works luvverly, and gives me proper frequency estimates. why ? there are no individuals in my PEDIN.DAT file with either a 2 or a 7 or a 11 allele, but ILINK doesn't complain. am i missing something stupid ? is ILINK stupid ? i've run a few tests, and it always craps out early if there is no "n" allele for an "n"-allele system. oh dear, woe is me. for both (1) and (2) i am using version 5.2 of LINKAGE on the pc. i am using a dos-pc, and will start using a lot of alcohol if i can't get these problems fixed. hhhhheeeeeeellllllllppppppp !! Iain "Help" Fenton, Cardiff, UK. From owner-gene-linkage@net.bio.net Wed Nov 16 22:00:00 1994 Path: biosci!ns1.faseb.org!darwin.sura.net!news.sesqui.net!rice!lcmp4.cs.rice.edu!schaffer From: schaffer@lcmp4.cs.rice.edu (Alex Schaffer) Newsgroups: bionet.molbio.gene-linkage Subject: Linkage Analysis Book Date: 17 Nov 1994 00:17:22 GMT Organization: Rice University Lines: 30 Message-ID: <3ae7ei$nvd@larry.rice.edu> NNTP-Posting-Host: lcmp4.cs.rice.edu For those of you who are still learning the techniques of linkage analysis (and I include myself in that category), I would like to bring to your attention an outstanding book: Handbook of Human Genetic Linkage by J. Terwilliger and J. Ott Johns Hopkins University Press, 1994. The book gives a deep and detailed explanation of most of the techniques of linkage analysis, illustrated throughout with detailed examples of how to use the LINKAGE programs. Almost all of the material that Terwilliger and Ott have on LINKAGE applies verbatim to FASTLINK. The stimulus for this message is that in recent days, several prospective FASTLINK users have asked why FASTLINK does not come with documentation that explains how to set up the input files and what the outputs mean genetically. All these issues and many more are covered at length in the book by Terwilliger and Ott. In contrast, the documentation that comes with FASTLINK focuses on installation, portability, differences between FASTLINK and LINKAGE, and detailed descriptions of some algorithmic aspects of the software. These issues are barely mentioned in the book. Alejandro Schaffer Rice University From owner-gene-linkage@net.bio.net Wed Nov 16 22:00:00 1994 Path: biosci!bloom-beacon.mit.edu!spool.mu.edu!howland.reston.ans.net!Germany.EU.net!EU.net!ub4b!idefix.CS.kuleuven.ac.be!infoserv.rug.ac.be!allserv!ddeforce From: ddeforce@allserv.rug.ac.be (Dieter Deforce) Newsgroups: bionet.molbio.methds-reagnts,bionet.molbio.gene-linkage,bionet.general Subject: fingerprint DNA Date: 17 Nov 1994 16:45:18 GMT Organization: University of Ghent, Belgium Lines: 22 Message-ID: <3ag1au$jts@infoserv.rug.ac.be> NNTP-Posting-Host: allserv.rug.ac.be Summary: bloodstain DNA Keywords: fingerprint,forensic,bloodstain X-Newsreader: TIN [version 1.2 PL2] Xref: biosci bionet.molbio.methds-reagnts:21109 bionet.molbio.gene-linkage:458 bionet.general:12014 Hello Can anybody tell me which is the best procedure to extract DNA from bloodstains in case of forensic analysis? Does anybody have data on the conservation of bloodstains and the degradation of DNA since we have had problems with DNA from bloodstains found on the scene of the crime. Is it possible that DNAse from the skin destroys the DNA? We are now using Chelex100 resins for the extraction. We have no problems with fresh blood or bloodstains but some older bloodstains are problematic. Does this come from our extraction or is it possible the DNA is too degraded? Scincerely Drs. Apr. Dieter Deforce E-mail : Dieter.Deforce@rug.ac.be Labo Farmaceutical Biotechnology Harelbekestraat 72 9000 Gent Belgium tel 09/221.99.43 fax 09/220.66.88 From owner-gene-linkage@net.bio.net Wed Nov 16 22:00:00 1994 Path: biosci!HAL.HAHNEMANN.EDU!rosenbergh From: rosenbergh@HAL.HAHNEMANN.EDU Newsgroups: bionet.molbio.gene-linkage Subject: need info. on effects of radioactive waste Date: 17 Nov 1994 14:58:08 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 5 Sender: daemon@net.bio.net Distribution: world Message-ID: <009879CC.3B2FD720.152@hal.hahnemann.edu> NNTP-Posting-Host: net.bio.net Hello! My name is Sondra and soon my chemistry class in school is having a debate about nuclear energy. I am supposed to take the standpoint of a genetesist, so any realted information on the subject would be greatly appreciated. Thank you, email me at: (the above address) From owner-gene-linkage@net.bio.net Thu Nov 17 22:00:00 1994 Path: biosci!ns1.faseb.org!darwin.sura.net!news.sesqui.net!rice!cs.rice.edu!schaffer From: schaffer@cs.rice.edu (Alex Schaffer) Newsgroups: bionet.software,bionet.molbio.gene-linkage Subject: FASTLINK for DOS available Date: 18 Nov 1994 01:09:13 GMT Organization: Rice University Lines: 154 Message-ID: <3agurp$hsh@larry.rice.edu> NNTP-Posting-Host: cs.rice.edu Xref: biosci bionet.software:10059 bionet.molbio.gene-linkage:459 The purpose of this note is to announce the availability of trial versions of FASTLINK for DOS. Thanks to Ramana Idury and Roger Kou at USC for figuring out how to convert the UNIX versions to DOS versions. FASTLINK contains significantly faster versions of the main programs in LINKAGE. Some fundamental similarities and differences between UNIX versions of FASTLINK and DOS versions of FASTLINK should be noted: Similarities: 1. DOS FASTLINK is essentially the same as FASTLINK 2.2, provided that the computer does not crash during the run. 2. Most of the documentation still applies except the instructions for installation (we distribute executables for DOS, so no compilation is required) and portability (basically irrelevant to DOS). 3. We are distributing versions of LODSCORE, ILINK, LINKMAP, MLINK, UNKNOWN. Other auxiliary programs can be obtained from the FTP site at Columbia. Differences: 1. We are distributing only executable versions for DOS FASTLINK, rather than source as for UNIX FASTLINK. Details about how to get the executables are given below. We may distribute source at a later date. 2. DOS FASTLINK does not support crash recovery. 3. We are distributing only the "slow" versions of FASTLINK for now. These are still measurably faster than LINKAGE. Cautions: 1. FASTLINK is derived from LINKAGE 5.1 for UNIX and not from LINKAGE for DOS. We have tested FASTLINK on DOS, but we have not investigated to what extent LINKAGE for UNIX and LINKAGE for DOS are incompatible. 2. If FASTLINK and LINKAGE give different answers, you should not assume that FASTLINK is wrong. LINKAGE may be wrong. I have fixed 2 significant bugs in LINKAGE LODSCORE/ILINK and 1 significant bug in LINKAGE LINKMAP/MLINK. These bug fixes are described in README.updates. There is also an inconsistency in scaling in LINKAGE LINKMAP, which is fixed in FASTLINK LINKMAP (see README.scaling). 3. You must a have 386 or higher machine. The code was tested on two different 486 machines. I am fairly certain that it won't work on 286 and below machines. 4. You should have a Math co-processor on the machine. Most recent 486 machines will have this. 5. We strongly recommend trying the programs outside of Windows (i.e., in vanilla DOS) first. They probably work from Windows too, but it may be the case that the compiler makes some assumptions about how the video/monitor environment is set up, which are not consistent with the setup of your machine. Like FASTLINK 2.0, 2.1, and 2.2, DOS FASTLINK is distributed by FTP from a computer at Rice University. I have not yet sorted out logistics for mailing out floppy disks. Here are the instructions for retrieving the code: ftp softlib.cs.rice.edu Login as anonymous and leave your full e-mail address as password. cd pub/fastlink/dos binary In that directory you will find various files. You may wish to retrieve all the files with the name README and all the files that end .ps. These are all relevant documentation files. The file README with no extension gives a roadmap to all FASTLINK documentation. Having retrieved whatever documentation you want you should retrieve: lo48.exe (LODSCORE with maxhap set to 48) lo96.exe (LODSCORE with maxhap set to 96) il48.exe (ILINK with maxhap set to 48) il96.exe (ILINK with maxhap set to 96) li48.exe (LINKMAP with maxhap set to 48) li96.exe (LINKMAP with maxhap set to 96) ml48.exe (MLINK with maxhap set to 48) ml96.exe (MLINK with maxhap set to 96) unknown.exe (UNKNOWN) maxhap is the maximum allowed product of number of alleles at all loci in the analysis. For example, if you want to do a 3-point analysis with allele numbers 2, 3, and 3, the allele product is 18 and it is safe to use the version with maxhap set to 48. If you wish to do a 4 point analysis with allele numbers 2, 3, 3, and 4, the allele product is 72 and you should use the version with maxhap set to 96. You should retrieve all 9 files. Remember to use binary mode in FTP. When you wish to run the programs decide which version you want to use and rename that to one of (lodscore.exe,ilink.exe,linkmap.exe, mlink.exe). Example: rename li96.exe linkmap.exe Note: the limitation of maxhap set to 96 is experimental, not inherent. The LINKAGE for DOS version distributed from Columbia use maxhap set to 48, which is why we chose that as the lower value. While testing out the code, we successfully tried a much larger value of maxhap (180) on a DOS machine with 16Mbytes of RAM. The decisions on how to set the constants in the executables we distribute will undoubtedly be revisited often based on user comments. Note: The DOS executable are not currently included in fastlink.tar.Z, so you must retrieve them as individual files. I would appreciate your feedback as to whether our DOS versions work on your machine. Our initial algorithmic improvements are described in the paper: R. W. Cottingham Jr., R. M. Idury, A. A. Schaffer. Faster Sequential Genetic Linkage Computations, American Journal of Human Genetics 53(1993), pp. 252-263. The algorithmic improvements from version 1.0 to version 2.0 of FASTLINK are described in the papers: A. A. Schaffer, S. K. Gupta, K. Shriram, and R. W. Cottingham Jr. Avoiding Recomputation in Linkage Analysis, Human Heredity, 44(1994), pp. 225-237. We ask you to cite both papers if you use FASTLINK in any published experiments. Both papers are included in the distribution. The code in this distribution is the result of complicated collaborative work in which all 5 authors of the above papers played significant roles. The most important changes from FASTLINK 2.0 to 2.2 are described in the file README.updates that comes with FASTLINK. FASTLINK is a modified version of LINKAGE. You should continue to cite the original papers on LINKAGE, if you use FASTLINK in a published experiment. I am maintaining a e-mail mailing list of FASTLINK users. If you have retrieved the code and would like to be on the mailing list, send me e-mail at the address below. Being on the mailing list is important to find out about corrected and improved versions of FASTLINK Alejandro Schaffer, PhD Department of Computer Science Rice University Houston, TX 77251 schaffer@cs.rice.edu Tele: (713) 527-8101 x3813 (I do not have a direct line) FAX: (713) 285-5930 From owner-gene-linkage@net.bio.net Fri Nov 18 22:00:00 1994 Path: biosci!agate!howland.reston.ans.net!swrinde!pipex!uunet!caen!hearst.acc.Virginia.EDU!portal.gmu.edu!osf1.gmu.edu!psubedi1 From: psubedi1@osf1.gmu.edu (Prakash Subedi) Newsgroups: bionet.molbio.gene-linkage Subject: Gene mapping and gel electrophoresis Date: 19 Nov 1994 21:13:27 GMT Organization: George Mason University, Fairfax, Virginia, USA Lines: 6 Message-ID: <3alppn$al@portal.gmu.edu> NNTP-Posting-Host: osf1.gmu.edu Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit X-Newsreader: TIN [version 1.2 PL2] Is gel electrophoresis used for gene mapping? If so, is there any newsgroup or any source on Internet that I can access? Does anybody know? Thank you [genius]. From owner-gene-linkage@net.bio.net Sat Nov 19 22:00:00 1994 Path: biosci!bloom-beacon.mit.edu!gatech!howland.reston.ans.net!vixen.cso.uiuc.edu!news.uoregon.edu!cs.uoregon.edu!usenet.ee.pdx.edu!not-for-mail From: rootd@ee.pdx.edu (Conan the Librarian) Newsgroups: bionet.molbio.gene-linkage Subject: bionet.molbio.gene-linkage FREQUENTLY ASKED QUESTIONS (part 2 of 3) Date: 20 Nov 1994 00:51:44 -0800 Organization: Portland State University, Portland, OR Lines: 501 Message-ID: <3an2n0$s6q@ka.ee.pdx.edu> NNTP-Posting-Host: ka.ee.pdx.edu however, uses a text interface, so you don't need a fancy x-window (or MacMosaic or WinMosaic) to browse the web (this is great when I dial in from home, and only have an ascii terminal). You can find lynx (and several other web-browsers) at ftp.isri.unlv.edu in /pub/mirror/infosystems/WWW/clients. Of course, you could always use archie to find other ftp sites with lynx. I can telnet to the internet. Can I access the web? [harper;22Jul94] Surprise surprise, not everyone has a workstation or Xwindows, and many scientists only have simple vt100 emulation on their desktop machine. They read about www, gopher, archie, etc, but due to hardware or software limitations they can not get at any of the goodies on the net. There are not many "public access" sites that allow you to open up a telnet session and then choose from the most popular services on the net today. Well for anyone who can open up a telnet session you can now play with the big boys even though your equipment is from the last decade. Give the command: telnet info.funet.fi and you will be presented with the following menu. Finnish University and Research Network FUNET Information Service The following information services are available: gopher Menu-based global information tool www World Wide Web, Global hypertext web wais Wide Area Information Server, global databases on on different topics x500 X.500 clients are on nic.funet.fi, login: dua, no password archie Database of Internet Archive contents exit Exit FUNET information services What www sites have useful genetic-linkage information? [rootd;21may94][rootd;19Nov94] http://www.genethon.fr the genethon center http://www.chlc.org the Cooperative human linkage center http://www.gdb.org/hopkins.html has a molecular genetics primer http:gdbwww.gdb.org has a very useful but restricted version of GDB available. It may also be possible to access OMIM without an account here--but I haven't tried it out. "http://www.ai.sri.com/people/pkarp/mimbd/rsmith.html/ has the Survey of Molecular Biology Databases and Servers http://mendel.berkeley.edu/dog.html is the home of the dog genome project. http://www.pathology.washington.edu has human and mouse standard idiograms.The idiograms are useful for making illustrations for gene mapping, i.e. physical, and for constructing abnormal chromosome illustrations, like translocations, deletions, etc. The PostScript versions produce high quality output - can be sent to lino for publication figures. The PostScript idiograms can be manipulated band-by-band with illustration software such as Adobe Illustrator, Aldus FreeHand, Canvas, Altsys Virtuoso, etc. What "linkage centers" make information and assistance available to researchers? [rootd;29may94] The cooperative human linkage center can be contacted at: gopher.chlc.org http://www.chlc.org (world-wide-web) ftp://ftp.chlc.org (ftp) info-server@chlc.org (an automated information service) or help@hclc.org (real humans!) We encourage people to use the info-server first, and then explore the gopher or www site before trying to contact a human at help. It will probably be faster too, since the humans at chlc are working on tons of neat projects. 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 linkage-server@chlc.org According to Bob Stodola at chlc: "Currently, our email server is fairly crude -- it does crimap two-point analysis and maps the data with respect to the CHLC markers. Our plan is to include a substantially enhanced version which replicates what CHLC is using in terms of data diagnostics and mapping information." And another center: I am David Featherston, from the Dutch EMBnet Node, where we are starting a linkage analysis service: software availability and support/advice (at first),and (if I ever get my Drosophila/F2 geneticists head wrapped around pedigrees and maximum likelihood) training and perhaps consultancy. At present, we have MapMaker/EXP 3.0b, MapMaker/QTL 1.1, Lathrop and Lalouel's Linkage programmes and Schaffer et al's Fastlink versions of ILINK, LINKMAP, LODSCORE and MLINK on offer. "On offer" means that if a user has a Genomics Package account at the CAOS/CAMM Center, they can use these programmes on our fast computers to analysetheir data sets. Anyone is welcome to contact me for information about what elseis included in a Genomics Package account, and for the details about opening one. Their ftp site is camms1.caos.kun.nl, and the email contact is davidf@caos.kun.nl What journals are useful for genetic linkage analysis? [Young Bae Choi put this on the net, I edited it--rootd,19may94] Journal of Computational Biology (New!) Editors: Michale Waterman and David Kingsbury Contact: dkinsbu@merlot.welch.jhu.edu or msw@hto.usc.edu Human Genome Project Journal (?) Contact: Tim Stearns tim@eeg.com Computer Applications in Biosciences (CABIOS) American Journal of Human Genetics Nature Genetics Genomics Human genome news, available by gopher from gopher.gdb.org Human Heredity, edited by Jurg Ott (jurg.ott@columbia.edu) GENE-LINKAGE SOFTWARE OVERVIEW What database management programs do people use for genetic-linkage data? [rootd;15may94] Paradox:This is a full database-management system available from Borland computer company for IBM machines. Like most other "full feature" databases, it is reliable and supported on most IBM platforms, but not tailored specifically to the needs of genetic researchers. It has a good educational discount. We use it, but have to repeatedly set up our report-formats for linkage output. Getting liped output format is nontrivial. Linksys: This custom-made database program was written by J Attwood and S Bryant. Although they continue to use it, John Attwood suggests using dolink instead. Linksys is not currently available at any ftp sites. Dolink: This DOS custom database program (by D Curtis I think??) manages genetic data and sets up input files for your analysis. It is available from ftp.bchs.uh.edu. 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 (according to the ad, not from personal experience) will draw pedigrees, haplotype marker data, and can output in linkage format. The demo did not work on our IBM because our monitor is from the stone age. We were able to get the demo to run on a Power-PC Mac with SoftWindows emulation, but it crashed the Mac when we hit the escape-key during the demo. Be forewarned: the list price is about $500. CEPH:This database is specifically designed for chromosome mapping with ceph-style-pedigrees. It can output data in ped.out format or linkage format. Our version (5.0) fails when we output over 90 markers, but not the entire dataset. Santosh Mishra wrote a program (called mkcrigen) which converted the ped.out files to .gen files. Unfortunately we only have an old binary which was compiled with a maximum of about 85 markers. If you try to convert a ped.out file to a .gen file with more than 85 markers, your final .gen file is messed up. Santosh Mishra modified the program to work with 500 markers, but we do not have any source code for mkcrigen (any version) and we do not have a binary for the improved version. Some other labs output the data in linkage format and convert that to .gen format. We don't like that because that separates the marker name from the marker data, and can result in errors. I believe that the ceph database is available on the ceph ftp site, but I do not have the address. [Also see the "What is Cryllic?" question] Please send comments on database programs you use! What programs are available for pedigree drawing? [rootd;16may94] peddraw (IBM version): This program (Possibly written by Dave Curtis) is a pedigree drawing program for IBMs available from ftp.bchs.uh.edu in the /pub/gene-server/dos directory. I have never used it. ftree: This is another IBM pedigree program written by Rodney Go at the University of Alabama. I have a copy, but do not know where this program is available. I don't use it, but some old pedigrees in a notebook look very pretty. peddraw (Mac Version): This program, written by B Dyke, P Mamelka, and J MacCleur, is available from: bdyke@darwin.sfbr.org Pedigree/Draw Department of Genetics Soutwest Foundation for Biomedical Research PO. Box 28147 San Antonio, TX 78228-0147 An upgrade from a previous version is $10 (current version = 4.4). Documentation costs $10 (get it). The full package including documentation costs $45. The best thing about (mac) peddraw is that the text file formats are included in the documetation. I have a sed-awk-sh script which converts linkage format to peddraw format, making generation of large pedigrees easy. My simple script is available via anonymous ftp at ftp.ee.pdx.edu in /pub/users/cat/rootd/convert.new Genetree: "The GeneTree 1.0 package provides a convenient way to draw family tree diagrams suitable for genetics or geneology using an IBM PC or compatible computer. The package consists of the GeneTree program, which draws pedigree diagrams using a command language, and SC, 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 the C programming language. 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) [Also see the "What is Cryllic?" question] Why are some programs used primairly for chromosome mapping, while others are used for disease-mapping? [rootd;15may94] 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. What programs are used for chromosome mapping? [rootd;21may94] crimap: This program has been used for chromosome mapping for years. It has options which can generate maps, calculate order probablities, 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 Phil Green (the author) has successfully run it on UNIX, DOS, VMS, and Macintosh systems. It is not available via anonymous ftp. multimap:This Lisp-based expert system uses an customized version of crimap to create a chromosome map. It is available via anonymous ftp from genome1.hgen.pitt.edu. The authors (T Matise, M Perlin, and A Chakravarti) continute to improve the code, add new functions, and provide excellent support. When used with the crimap 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 crimap version (called lispcri) is distributed at the ftp site, but was not meant to be used independently of multimap. mapmaker: MAPMAKER Dr. Eric Lander Whitehead Institute 9 Cambridge Center Cambridge, MA 02142 mapm%mitwibr@mitvma.mit.edu CHROMLOOK: This is somewhat similar to chrompic-crimap (I hear that the output is easier to read). It takes input files in the liped format. It was written by Jonathan Haines, and I currently do not have an ftp site for this program. clinkage: This is the special version of the LINKAGE programs for 3-generation (CEPH) pedigrees and codominant markers. PC version available by ftp from york.ccc.columbia.edu. Unix version from corona.med.utah.edu. a What programs are used for disease-gene mapping? [rootd;21may94] LABMAN and LINKMAN are made available free of charge (via anonymous ftp) by Dr. Phil Adams of Columbia University. I don't know what they do, or what the specific ftp site is, but a paper reference is: Genetic Epidemiology (1994, vol. 11, no. 1, pp. 87-94. Simlink: This fortran program (by L Ploughhman and M Boehnke) simulates linkage analysis on a family, and gives you an "estimate the probability, or power, of detecting linkage given family history information on a set of identified pedigrees." It allows the researcher to determine whether a family has sufficient informativeness to detect linkage. In addition, it can help the researcher to decide how far apart to seperate their genetic probes without "missing" the disease locus (ie. Do I use probes seperated by 30cM? or will 40cM be close enough given the informativeness of this family). This can save the researcher considerable time and money. The researcher won't waste money doing a genome search on an insufficiently-informative family. Large families can be "trimmed" during the initial genome-search, and then the entire family can be used later during marker-localization. Simlink data can be useful on grant applications (to prove that the family you propose to analyze is sufficiently informative). Simlink requires large quantities of memory. It was written for IBM's, but has been ported to many platforms including: Sequent symmetry S8000's. It is available from: Michael Boehnke Michael.Boehnke@um.cc.umich.edu 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 (Thanks Dr. Boehnke!) Simlink "may" be available via anonymous ftp "soon" Slink: This Pascal program (by D Weeks, M Lathrop, J. Ott) 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. Available from york.ccc.columbia.edu or on floppies (see Linkage). Liped: This IBM program (written by Jurg Ott) calculates probabilities for genetic linkage between disease-markers and genetic-markers. It's 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). Cathy Falk writes: There ARE a couple of versions of Liped around that work on the Sun, but each one seems to have its own developmental path (from the original), so it's not so easy to describe. We have a version that came from UCLA (Dr. Anne Spence) which we have had running on the Sun for some time. It accepts up to 6 alleles per locus, and we now want to increase that. It also has a somewhat different structure for the input files. Dr. Peggy Pericek-Vance, at Duke, has a version that accepts up to 8 alleles, but it is a modification of an earlier LIPED and is not totally compatible with our current (UCLA) version. Dr. Ott has a PC version which he thinks would be easy to modify for the Sun, and Dr. David Greenberg informed me that he has a version for DEC (VMS) machines. GREGOR: is a piece of software (IBM PC compatible) 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 a "pkzip" archive called "pub/McGill- Contrib/GREGOR.ZIP". Further information can be found in the following reference: N.A. Tinker and D.E. Mather. 1993. GREGOR: software for genetic simulation. J. Hered. 84(3):237- 238. Questions should be directed to the authors: (tinker@agradm.lan.mcgill.ca or mather@agradm.lan.mcgill.ca). [thanks to tinker for sending this--rootd] Linkage: This package of programs, developed by Mark Lathrop with help from JM Lalouel, C Jlier, and J Ott. Jurg Ott maintains the IBM versions. The Linkage package consists of several analysis programs (each of which do a particular type of analysis) and several utility programs (which make the analysis programs easy to use). Versions are available for IBM's and unix platforms. Here are some of the analysis programs: mlink: 2-point lod-score calculations at fixed recombination distances linkmap: multipoint lod-score calcuations at fixed distances ilink: calculates the recombination distance with the highest lod-score Unix versions are available from corona.med.utah.edu PC and VMS versions are available from york.ccc.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 a bunch of preformatted IBM disks if you request linkage by mail. Jurg Ott (jurg.ott@columbia.edu can send you more information regarding mail-requests for the linkage package). fastlink: This is a port of the linkage package to C (by A Schaffer, R Cottingham, and R Idury). The initial port increased the speed by an order of magnitude. They continue to optimize the algorithm and code, resulting in continued speed improvements. In addition, 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 a ton of memory, but uses that memory to contain some of the intermediate results which are repetitively recalculated in the "slow" version (and the old linkage package). We obtain good results by setting up 300 megs of virtual memory on our sparc and using the fast version (at one point we ran a fastlink linkmap run with 700 haplotypes). The fastlink programs are also more portable. Earlier versions of fastlink required installation of p2c (the free-software foundation's pascal-to-C converter). That is no longer necessary. Affected Pedigree Member Method package by Dan Weeks and available via anonymous ftp from watson.hgen.pitt.edu. Here's some info that Dr. Weeks sent me: The Affected Pedigree Member Method distribution contains the new APM programs, a new file conversion utility, and a histogram/statistics generator (all of which are version 2.0). To build the entire distribution, you need C, Pascal, and Fortran compilers. A make utility is also helpful. Instructions on building the distribution are in the file HowTo. Please read the file READ_ME_FIRST before doing anything. For an introduction to the APM programs, read the Intro file. For a list of known bugs, read the BUGS file. 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 multi-locus 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 hist, a program to compute various statistical figures, plot a histogram, and compute empirical p-values emaillink: I was working on a system to allow people to submit FASTLINK runs via email, but it's on indefinite hold while I work on classes and stuff. Perhaps I'll get back to it someday--rootd. What programs are available to help detect errors in linkage data? By linkage data, I mean any genetic-linkage dataset, not just those for the Lathrop Linkage package. This is an important question, and I simply do not know the answer. I've used the crimap-chrompic option, and played with xpic/phap a little bit, but I really hope some people send me some information on this topic. What is Cyrllic? [P Janssens; 22may94] Cyrillic is a pedigree editor, with facilities for including marker data, you can then ask it to interface with LINKAGE, i.e. it creates the input files for MAKEPED, and runs the whole show. 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, DNA numbers, etc. If you want I can email you version 1.11, to have a look at. They also have technical support by email from Oxford. Let me know if you are interested. I had to learn to use the program here, and teach everyone else in the lab. Just before I started working here they had bought it. I also had to learn the old way of preparing the datain files for MAKEPED, and I promise you that I will never look back. There were some serious bugs in version 1, but as far as I can tell it has all been fixed quite nicely. There are of course some features that they are still busy implementing, but it is an excellent interface with LINKAGE! What programs help me recode genetic markers? [dcurtis;20Jul94] If anyone's interested, DOLINK can downcode alleles automatically. I'm not sure if it uses the same algorithm as Ott's, but it's described in the documentation along with potential drawbacks. The main use of DOLINK is to prepare files for LINKAGE etc. from a database. It's at diamond.gene.ucl.ac.uk in /pub/packages/dcurtis. I've _nearly_ got a version ready to run under X (current is only for DOS) + I will try to accelerate this if there is huge public interest. LINKAGE PACKAGE SPECIFIC INFORMATION How do you calculate MAXHAP? [rootd;15may94] 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 the loci in your dataset, just the loci you use). Remember that affection status counts as two alleles, regardless of the number of liability classes. For example, if a dataset has the following information: affection status: 4 liability classes Marker A: 3 alleles marker B: 4 alleles marker C: 5 alleles And your run includes a linkmap run between affection-status, A, and B, then your MAXHAP must be (at least) 2*3*4 When should you use binary coding instead of numeric allele coding? [Gerard Tromp;29may94] Usually, there is no advantage to coding disease or loci as either binary or numeric using liability classes. Generally binary coding is more complex in that we humans have a hard time thinking that way. Some co-dominant phenotypes lend themselves to binary coding e.g. ABO bloodtypes: A - 1 0 1 B - 0 1 1 O - 0 0 1 AB - 1 1 1 unk - 0 0 0 in this case, one codes the O type factor as present in all cases except unknowns. Since one cannot distinguish AO from AA at the phenotype level one codes both genotypes as 1 0 1, presence of A and O. In reality O represents absence of both A and B. One can however not code that using 0 0, since 0 0 would be an unknown. Use of binary codes has decrease since DNA markers have come into use, as they allow one to type an individual with respect to genotype. From owner-gene-linkage@net.bio.net Sat Nov 19 22:00:00 1994 Path: biosci!bloom-beacon.mit.edu!gatech!howland.reston.ans.net!vixen.cso.uiuc.edu!news.uoregon.edu!cs.uoregon.edu!usenet.ee.pdx.edu!not-for-mail From: rootd@ee.pdx.edu (Conan the Librarian) Newsgroups: bionet.molbio.gene-linkage Subject: bionet.molbio.gene-linkage FREQUENTLY ASKED QUESTIONS (part 1 of 3) Date: 20 Nov 1994 00:50:10 -0800 Organization: Portland State University, Portland, OR Lines: 513 Message-ID: <3an2k2$s4h@ka.ee.pdx.edu> NNTP-Posting-Host: ka.ee.pdx.edu BIONET.GENE-LINKAGE FREQUENTLY-ASKED-QUESTIONS By Darrell Root rootd@ee.pdx.edu FAQ admin information Where can I obtain the bionet.molbio.gene-linkage FAQ? Who created the bionet.molbio.gene-linkage FAQ? What other people contributed to this FAQ? How can I help improve this FAQ? What kind of information will never be contained in this FAQ? Information Resources What anonymous-ftp sites have programs/utilities useful for genetic linkage analysis? I think I know the name of a program I want, but I don't know where I can find it I have an ftp site with gene-linkage programs/utilities on it. How do I get registered with the archie servers? What gopher sites have useful genetic-linkage information? What books are helpful when learning about genetic linkage analysis? What genetic-linkage databases are available on the internet? What is WWW? What is Mosaic? What is lynx? I can telnet to the internet. Can I access the web? What www sites have useful genetic-linkage information? What "linkage centers" make information and assistance available to researchers? What journals are useful for genetic-linkage analysis? Gene-linkage software overview What database management programs do people use for genetic-linkage data? What programs are available for pedigree drawing? Why are some programs used primairly for chromosome mapping, while others are used for disease-mapping? What programs are used for chromosome mapping? What programs are used for disease-gene mapping? What programs are available to help detect errors in linkage data? What is Cyrllic? Programs to assist in the recoding of genetic markers Linkage package specific information How do you calculate MAXHAP? When should you use binary coding instead of numeric allele coding? What is the effect of having allele frequencies not add up to 1, eg. when some alleles are not present in a pedigree under study? I use LINKAGE and/or FASTLINK. What references should I include in my papers? A discussion of recoding alleles in linkage analysis Computer administration and optimization How can I increase the speed of the linkage/fastlink package on my workstation? I set up 300 megs of paging space on my workstation, but now I'm running out of hard-drive. Is there any way I can use my hard drive space more effeciently? But I don't know how to do all this optimization, and my research assistant is spending all his/her time trying to figure it out. How can I identify how much paging space is available on my workstation? File format specification and conversion How do I convert between crimap and linkage formts? How do I get my ceph data into crimap format? Educational resources for teaching genetics Genetics construction kit--fly genetics simulator FAQ ADMINISTRATIVE INFORMATION Where can I obtain the bionet.gene-linkage FAQ? [rootd;29may94] It is available by anonymous-ftp from: ftp.ee.pdx.edu in /pub/users/cat/rootd The best way to view the faq is via the www, from http://www.ee.pdx.edu/~rootd/gene-linkage.html I also send the FAQ to news.answers, and to Dave Kristofferson, so it should be included in the "standard" FAQ archives. Of course, I won't be able to test that till after this goes out :-( Who created the bionet.molbio.gene-linkage FAQ? [rootd;19nov94] I am Darrell Root, and I'm editing this in my own time. Unfortunately, I don't have all that much free time, so this FAQ is sorta haphazard and has some obvious holes (for example, some of the "software packages for linkage analysis" answers point out ftp sites which are not included in the "ftp site list". In addition, I haven't double-checked much of the information which I received from people (and I may have made a typo or two), so if something appears incorrect, you're probably right. Many thanks to everyone who sent me tons of information after the FAQ revision 1. Unfortunately, that's when things started to get "busy" and I'm just now doing the update (SIX MONTHS LATER). In addition, I moved the faq www site from http://www.ee.pdx.edu/rootd/gene-linkage.html to http://www.ee.pdx.edu/~rootd/gene-linkage.html Sorry about that. Tim Trautmann (timt@ee.pdx.edu) adapted the FAQ for www/Mosaic use (before I learned html). He's responsible for all the wonderful hypertext/ftp links. Great work Tim! (I'm afraid my hurried edits to get this revision out have not been perfect, and the FAQ's formatting is a little messed up--this is entirely my fault due to my haste: timt's formatting was perfect...) This FAQ is not perfect, in fact, it's not even pretty. During my 18 months doing linkage analysis work, I searched the net trying to find stuff, and used up a bunch of time. This FAQ is sufficiently disorganized that it may take you half-a-day to sort through it, but I hope that will save you some time. On a personal note, I'm continuing my career as a system administrator, and am no longer doing genetic linkage analysis. If I have time, I'll incorporate corrections/additions that people email me (rootd@ee.pdx.edu), but I'm not actively searching/editing the faq. In addition, someone who is doing linkage analysis would almost certainly do a better job (assuming they have the time :-). For this reason, I'm placing this FAQ in the public domain so anyone who wants to take over editing it can do so without restriction. If you have the time, and want to be a FAQ maintainer, send me some email. My eternal thanks to those who sent me information. My repeated apologies for not updating the FAQ for six months. What other people contributed to this FAQ? [rootd;21may94] Matthias Wjst sent us tons of useful material David Kikuchi pointed out the genbank gopher sites Pierre Janssens forwarded me some usenet answers, and described Cyrillic. Bennett Dyke provided information on his version of peddraw. Michael Boehnke supplied a postal address to obtain simlink. Don Bowden gave us a lead in finding a .gen->linkage converter. Young B Choi posted a list of journals to the net. Robert Stodola sent us info about the chlc. Ellen Wijsman gave a nice answer to the allele frequency question on the net. Jurg Ott sent us tons of corrections, clarifications, and new information. Peter Doris helped identify a problem with our ftp site. David Adler told us about the idiograms at the University of Washington. Tim Littlejohn posted a gopher site with conference schedules. John Attwood put his ceph2cri program on the net. Rob Harper posted how people can use telnet to access the WWW. David Featherstone sent info about fastlink on SGI's, and on CRI-MAP Dave Curtis posted about DOLINK, the automatic recoder. Kim Worley posted a web site. Mike Miller sent me some info on LABMAN and LINKMAN. Tara Matise sent me 18 separate pieces of information! Thanks! Eli Meir posted about the Genetics Construction Kit (fly genetics simulator). I'm afraid some other people sent me stuff, some of which was included, and some of which was lost (been a hectic half-year). My apologies. Feel free to send me some nasty email (or a correction, or to claim credit for something. How can I help improve this FAQ? [rootd;19may94] Think back to the old times. What do you understand now, that you didn't understand then? What lack of knowledge caused you to waste the most time? What information would have helped you become productive more quickly? Share your hard-earned lessons with others! There are a couple areas where I'd like to specifically request assistance: 1. Internet resources: there are tons of ftp/gopher/www sites out there. Nobody knows them all. Help me compile a complete list. Send me the site addresses and a brief description of what's there. 2. File format conversion programs: I want programs to convert between the diferent file formats (crimap's .gen, ped.out, linkage, simlink, peddraw (mac) liped etc...) I'd like to compile a "complete-set" of file conversion programs. I particularly want source for Santosh Mishra's mkcrigen (ped.out -> .gen) program. 3. An ftp site for crimap, simlink, mkcrigen, and the crimap utilities package 4. Programs for manipulation, analysis, and comparison of .gen files 5. I'd like plenty of "linkage-101" and "crimap-101" questions. What did you waste most of your time on? 6. If somebody wants to formally specify some of the file formats, and give a small example (or two) for each, I'd appreciate it. What type of information will never be contained in this FAQ? [rootd;21may94] Conference schedules/information (too volatile for a FAQ, let the journals handle it...but there's a nice gopher site in our gopher section :-) I sent you some information, and you either: didn't include it, or didn't give me credit. What can I do? [rootd;29may94] Oops. My mistake. I tried to keep a list of everyone and their contribution, but didn't completely succeed (translation: I failed). My apologies. Send me email and I will make appropriate corrections... INFORMATION RESOURCES What anonymous-ftp sites have programs/utilities useful for genetic linkage analysis? [rootd;29may94] corona.med.utah.edu keeps a UNIX version of LINKAGE (Lathrop/Lalouel/Julier/Ott). They also keep have the PC version, but it doesn't appear to have been updated since July-1991. york.ccc.columbia.edu has the PC and VMS versions of LINKAGE, and also other programs such as HOMOG, LIPED, SLINK, and some programs from Dr. Newton Morton (LDB, MAP-LODS, POINTER). In addition, all Linkage Newsletters are kept online. softlib.cs.rice.edu has FASTLINK, the optimized C versions of linkage(5.1) which continue to undergo massive improvements. ftp.gdb.org has some stuff in /non-gdb-data/NIH-CEPH-data/CEPH-DATA/src, including possibly the CRI-MAP utility programs (by Todd Steinbrueck of Helen Donis-Keller's lab). genome1.hgen.pitt.edu has Multimap, a lisp-based expert system for automated construction of genetic linkage maps using the CRI-MAP program. watson.hgen.pitt.edu has some stuff from Dan Weeks, including his APM programs and SLINK. Here's the info he sent me: At watson.hgen.pitt.edu, you'll find the following files in the pub directory after logging in via anonymous ftp: newapm.tar.Z contains the package of programs for the Affected Pedigree Member (APM) Method of Linkage Analysis. slink.tar.Z contains the SLINK package of programs for simulation of genetic data. cintmax.tar.Z contains a modified version of CILINK which permits the usage of different map functions in computing the likelihood. simapm.tar.Z contains 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. ftp.bchs.uh.edu has some useful IBM programs, including: peddraw (a DOS pedigree drawing program--completely different from the B. Dyke MacIntosh peddraw 4.x) fastmap produces a quick approxomation to multipoint lod scores dolink A DOS genetic database/analysis-setup program easistat A simple DOS statistics package easigraf Draws graphs of lod scores ftp.gene.ucl.ac.uk has the above IBM programs, as well as the ceph2cri program from John Attwood. ceph2cri reads your ped.out file and creates a crimap .gen file for you. ftp.chlc.org is the Cooperative Human Linkage Center's ftp site. prep.ai.mit.edu is the home of GNU (the free software foundation) which produces free software (such as the gcc compiler, and the emacs editor). wuarchive.wustl.edu is the largest anonymous ftp-site on the planet. They have the whole GNU/free software foundation distribution, and tons of other stuff. ftp.gdb.org has all the files for OMIM (online mendelian inheritance in man) and GDB (genome-data-base). Searching within the search program is much easier. ftp.ncsa.uiuc.edu has telnet, gopher, and mosaic clients for many different types of computers. Ever wonder where "ncsa telnet" was from? This is it. ftp.ee.pdx.edu in /pub/users/cat/rootd is where I put the latest FAQ version, my linkage->peddraw sed/awk script, and any other stuff that program authors decide to let me put on my ftp site. NOTE: crimap and simlink are not currently available from anonymous ftp sites. There are many more sites with useful stuff. Email information to rootd@ohsu.edu and I will add them to this list. I think I know the name of a program I want, but I don't know where I can find it. [rootd;21may94] There is a database program called archie, which maintains a list of all files in registered anonymous-ftp sites. You can telnet to an archie server, and have it search the database. Each site is updated every 30 days, so very recently posted programs might not be listed yet. To use archie, you need to telnet to one of the archie server sites, which are: archie.rutgers.edu archie.sura.net archie.unl.edu archie.ans.net archie.mcgill.ca (thanks to O'Reilly's Internet book for this list) Use the login name "archie" and nothing as your password. Here is a simple archie login an search: bigbox% telnet archie.unl.edu login: archie password: <--just hit return, not like anonomous-ftp unl-archie> find linkmap # Search type: sub. # Your queue position: 2 # Estimated time for completion: 00:24 working... - Host gatekeeper.dec.com (16.1.0.2) Last updated 21:04 9 Apr 1994 Location: /contrib/src/pa/m3-2.07/src/driver/boot-DS3100 FILE -rw-r--r-- 4000 bytes 23:00 2 Jun 1992 M3LinkMap_i.c FILE -rw-r--r-- 14027 bytes 23:00 2 Jun 1992 M3LinkMap_m.c Location: /contrib/src/pa/m3-2.07/src/driver/linker/src FILE -rw-r--r-- 1307 bytes 00:00 4 Dec 1991 M3LinkMap.i3 FILE -rw-r--r-- 3078 bytes 00:00 4 Dec 1991 M3LinkMap.m3 unl-archie> Unfortunately, these linkmap programs have nothing to do with Lathrop and Ott's linkage package. Most gene-linkage programs are not on archie-registered ftp sites. I have an ftp site with gene-linkage programs/utilities on it. How do I get registered with the archie servers? [rootd;15may94] send email to archie-admin@bunyip.com with the domain-name of the ftp site and the email address of the administrator. If you are the administrator of the ftp-site identify yourself as such. What gopher sites have useful genetic-linkage information? [rootd;21may94] gopher.gdb.org has background information on the human genome project, and archives of the "Human Genome News" newsletter. ftp.bio.indiana.edu is also a gopher site which can access genbank It also has a link to the genethon gopher site. gopher.genethon.fr is the genethon gopher site. ftp.nih.gov is the National Institute of Health gopher. It can access genbank, as well as other stuff. gopher.nih.gov is also a gopher site which can access genbank gopher.chlc.org has all information released by the cooperative human linkage center. larry.pathology.washington.edu 70 (I think that's a port number) has human and mouse standard idiograms. The idiograms are useful for making illustrations for gene mapping, i.e. physical, and for constructing abnormal chromosome illustrations, like translocations, deletions, etc. The PostScript versions produce high quality output - can be sent to lino for publication figures. The PostScript idiograms can be manipulated band-by-band with illustration software such as Adobe Illustrator, Aldus FreeHand, Canvas, Altsys Virtuoso, etc. megasun.bch.umontreal.ca has information on conferences, and other stuff in: --> 5. Computational Molecular Biology- programs, documents, help/ --> 14. Upcoming-Conferences/ What books are helpful when learning about genetic linkage analysis? [rootd;21may94] Jurg Ott's Analysis of Human Genetic Linkage is THE work in this area, It is available from Johns Hopkins University Press ($47.50) J.D. Terwilliger & J. Ott, "Handbook of Human Genetic Linkage," Johns Hopkins University Press, 1994, $60. It grew out of the handouts for the linkage courses and provides detailed instructions on how to use the LINKAGE (and some other programs) on a PC. Guide to Human Genome Computing, edited by Martin J. Bishop, and published by Academic Press (1994). It is very internet-oriented. The first chapter talks about ftp sites, etc. and Chapter 3 is dedicated to linkage analysis.($40) E.A. Thompson: "Pedigree Analysis in Human Genetics", Johns Hopkins University Press, Baltimore and London, 1986 ($35). K.E. Davies (editor): "Human Genetic Diseases - A Practical Approach". IRL Press, Oxford England and Washington, D.C., 1986 ($25, softbound; $40, hardbound). Muin J Khoury, Terri H Beaty, Bernice H Cohen. Fundamentals of Genetic epidemiology. Oxford University Press 1993, Monographs in epidemiology and biostatistics, Volume 19. "A good introductory book with 339 pages (att:several mistakes)" Please send me other suggestions. What genetic-linkage databases are available on the internet? [rootd;21may94][timt;09June94][rootd;19nov94] medline is a database for searching for articles in journals. If your site is a member of NorthWestNet, you can get to medline using telnet. Just telnet to uwin.u.washington.edu and go into the library databases. It can even email you the output if you wish! Many libraries and many internet service providers have medline services online. Some interfaces are better than others (we don't even bother using the one at OHSU--it's too painful...) Your local library can probably supply you with information. [cgochiku;2Aug94] posted this: For those of you out there with Macs who use MEDLINE and would like a way to put those text files of downloaded references into a database, check out medline-hc.sit in the Stanford archives. It is a hypercard stack I wrote that allows fast importing of references, including the abstracts. The file is at sumex-aim.stanford.edu /info-mac/sci/medline-hc Victor McKusick wrote a book: Mendelian Inheritance in Man. It is continuously updated online at Johns-Hopkins University (making it online-MIM or OMIM). Combined with the Genome- Data-Base, it is available via ftp at ftp.gdb.org You need to get an account. Send email to help@gdb.org for information. After you get an account, the telnet address is gdb.org The GDB www address is gdbwww.gdb.org, which has a useful but restricted version of GDB available. Here's an old workshop announcement that might be useful: IMPLEMENTATION OF THE INTEGRATED GENOMIC DATABASE Organised by The Biocomputing Centre at DKFZ Heidelberg 13-14th October 1994 The Integrated Genomic Database (IGD) is an international project to develop an information management system for human genome researchers which interconnects existing molecular biology databases and analysis tools. IGD is designed as a network system based on a client/server architecture. With regard to the origin and scope of data, the system can be subdivided into three levels: 1) resource databases which contribute data 2) target database servers which manage the integrated data 3) front-end clients which manage data locally to the user. Users need to install the IGD front-end on a local workstation for interacting with the IGD system. The most important parts of the front-end are the local database manager and the interfaces to communication and analysis. Users can query the IGD servers and download the resulting data into their local database,where it can be manipulated and analysed. Private data and analysis results may also be deposited into the local database. Registration of the workshop: 12th October, 18.00-20.00 For further information and details of accommodation please contact: Mrs. Anke Retzmann Dept. of Molecular Biophysics Im Neuenheimer Feld 280 69120 Heidelberg Germany Tel.: +49-6221-422372 Fax.: +49-6221-422333 E-mail: a.retzmann@dkfz-heidelberg.de What is WWW? [rootd;16may94] WWW stands for world-wide-web. People set up www servers (similar to anonymous ftp servers) that you can browse through. The webspinners (people who set up web sites) include "links" to other related sites. All you have to do is click a mouse-button on the link, and you will immediately go to the other site. The CEPH www site, for example, has a link to the genethon www site. This makes it very easy for you to get related information. My favorite www site has the before-repair and after-repair Hubble telescope pictures side-by-side. What is Mosaic? [rootd;16may94] Written by NCSA (the National Center for Supercomputing Applications) this program lets you look through www sites. It can spawn viewers to look at graphical data, output sound data on your computer's speaker (if your computer has a speaker), save your "favorite" www sites between sessions, and access automated www-search-engines (which search the www for you--similar to archie). What is Lynx? [rootd;19nov94] Lynx is another world-wide-web browser (like Mosaic). Lynx, From owner-gene-linkage@net.bio.net Sat Nov 19 22:00:00 1994 Path: biosci!agate!howland.reston.ans.net!vixen.cso.uiuc.edu!news.uoregon.edu!cs.uoregon.edu!usenet.ee.pdx.edu!not-for-mail From: rootd@ee.pdx.edu (Conan the Librarian) Newsgroups: bionet.molbio.gene-linkage Subject: bionet.molbio.gene-linkage FREQUENTLY ASKED QUESTIONS (part 3 of 3) Date: 20 Nov 1994 00:52:58 -0800 Organization: Portland State University, Portland, OR Lines: 470 Message-ID: <3an2pa$s8q@ka.ee.pdx.edu> NNTP-Posting-Host: ka.ee.pdx.edu One can use binary codes if one has phenotypic data which does not allow one to discriminate the underlying genotype exactly and one can code it as the presence (1) or absence (0) of factors such as the A and B antigens. Most disease locus data can be coded very effectively using affected/unaffected and appropriate liability classes. Hope the explanation is sufficiently clear. (and another answer from Jurg Ott) Binary factor notation allows representing loci with codominant and dominant mode (full penetrance) of inheritance while 'allele numbers' 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 (complete or incomplete penetrance). The main reason why binary factor notation is used is probably that CEPH's database is in that notation. Jurg Ott What is the effect of having allele frequencies not add up to 1, eg. when some alleles are not present in a pedigree under study?[Ellen Wijsman;16may94] 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+1th allele, use 1 minus the sum of the frequencies of the observed alleles. I use LINKAGE and/or FASTLINK. What references should I cite in my papers? FASTLINK: As described in the papers: 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. and A. A. Schaffer, S. K. Gupta, K. Shriram, and R. W. Cottingham, Jr., Avoiding Recomputation in Genetic Linkage Analysis, Human Heredity, to appear. [NOTE, this has appeared, so get the correct reference from the current linkage distribution--rootd] In addition, all fastlink users should also cite the LINKAGE papers: G. M. Lathrop, J.-M. Lalouel, C. Julier, and J. Ott, Strategies for Multilocus Analysis in Humans, PNAS 81(1984), pp. 3443-3446. 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. 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. A discussion of recoding alleles in linkage data From: wijsman@max.u.washington.edu Newsgroups: bionet.molbio.gene-linkage Subject: Re: Large Allele numbers Date: 11 Jul 94 21:35:13 PDT Organization: Lines: 96 Distribution: world Message-ID: <1994Jul11.213513.1@max.u.washington.edu> NNTP-Posting-Host: max.u.washington.edu >> In my group we are scanning the human genome for genes responsible for a >> complex disease. Not too far into the search, we have run into a few >> markers which have 16 or more alleles. I have been able to modify the >> LINKAGE programs (v 5.2) to allow up to 14 alleles, but past that, I get >> compiling errors informing me that I am out of memory. Further >> examination >> tells me that the UNKNOWN program creates a matrix of the size: >> (maxall)*(maxall+1)/2 X (maxall)*(maxall+1)/2 >> which is too big for DOS to handle. >> >> My question is, is there any way to get around this limitation by >> splitting >> up the pedigree set, or some other method? >> > >Tim Magnus writes: > >Conservative renumbering will allow you to renumber each family down to >4 alleles. The founding parents get 1 through 4. Each time a spouse >marries in, the spouse gets the two alleles missing from their mate. >(of course - if the alleles are the same size they are numbered the same >so you will not use all 4 alleles in every mating). > This type of renumbering is only possible when the genotypes in the founders are known, which is frequently not so for complex diseases. In fact, in human genetics with the exception of marker mapping in CEPH-type pedigrees, it is typical that there are some missing genotypes in founders. Thus the simple answer to renumber alleles usually does not fix the problem. >Jonathon Haines writes: >This is a recurring problem that has been vexing the genetic linkage >community for many years. The basic problem is to preserve the genetic/ >segregation information while reducing the number of alleles to a range >that allows easy computation. The method of recoding (recycling) alleles >described by Ott (AJHG, 1978) works very well, but can only be done when >the mode of inheritance of the disease is known (thus allowing the recoding >of spouses). 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 labelling 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. If the marker >in question has 14 alleles in the general population, but only 9 alleles >in the study population, it is possible to reduce the functional number of >alleles to 9 or 10. For the former, we usually adjust the allele >frequencies to sum to 1 by dividng each allele freqeucny 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 we know 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. As Jonathon noted, the multiple-allele problem is a big problem in analysis. The multiple allele problem became one of our biggest bottlenecks since we were analyzing families individually to reduce the number of alleles in the analysis. Our partial solution was the following. We use LIPED instead of LINKAGE for general 2-point analyses for a number of reasons which I won't go into. We modified LIPED so that if we assume a codominant marker and that alleles are labelled in a predetermined sequence (which we force through a preprocessor program), we can reread the specific observed alleles and their frequencies for each family. The program then assumes one more allele per family to account for all the other alleles at the locus. For genomic screening we don't do any downcoding (although we do downcode by hand for multipoint analyses and analyses with multi-looped pedigrees for which even 6 alleles is often too many). But these program modifications to allow us to process all our families together with only the observed number of alleles (plus one) per pedigree had an enormous effect on our ability to throughput most analyses relatively quickly. It is relatively unusual that we find more than 6-7 alleles in any one pedigree, which brings computation time (and memory requirements) down to reasonable levels. Thus for 2-point analyses downcoding is usually not necessary. I should note that we do our analyses on a workstation, but I don't see any reason that the modifications we made should not work on a PC, assuming the fortran is compatible. Ellen Wijsman Div of Medical Genetics, RG-25 and Dept of Biostatistics University of Washington Seattle, WA 98195 wijsman@u.washington.edu COMPUTER ADMINISTRATION AND OPTIMIZATION How can I increase the speed of the linkage/fastlink package on my workstation? [rootd;15may94] [aha, finally a question I can confidently answer!] 1. Use fastlink (it will increase your speed by an order of magnitude) 2. Setting up tons of paging space (using the hard-drive as virtual memory) and use the "fast" versions of fastlink. 300 megs is usually plenty. Note that paging space is the same as swap space. 3. Use gcc (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. 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 which you need. This is a task for an experienced system administrator. 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 insufficent for your system (so you were forced to install the generic kernel) 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 (on suns it reduces the priority level by 3 out of a total range of 40). Either do the runs in the foreground (which is fine as long as you don't plan to log out) or you can use the root password to renice 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 (distributed by GNU/free software foundation) 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, renicing below -10 can interfere with the operating system and actually reduce the process' speed. I just run them at a priority/nice level of 0 (the standard default level). That gives me reasonable response with my other applications, but still lets fastlink run at a decent speed. 7. Run with 100% penetrance 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" (decisions like this are why the professors make the big bucks :-) 8. Change the block size of your filesystem (from Gerard Tromp) One can increase performance of a filesystem by increasing the block size -- this decrease the number of read-write operations. A block device such as a hard disk usually accesses a block of data simulataneously. Thus if one is expecting to use large files, having large blocks will be an advantage. Simultaneously though 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 e.g. 2048. That is, each file or part of a file occupies 2048 bytes, a file of 100 bytes will still occupy 2048 bytes. i.e. Bigger blocks == faster bigger blocks => bigger fragments == more lost space. bigger blocks, allows for more cylinders per group. Related: see: newfs (8) - create a new file system for details on default values for file systems: inode -- 2048 bytes/inode block -- 8192 bytes/block frag(ment) -- 1024 bytes/fragment Gerard Tromp notes that you can increase the speed of programs which create/access large files in the /tmp directory by creating a tmpfs filesystem. The stuff is complicated and I haven't fully assimilated/understood his email yet, so I'm not including it yet. I'll be happy to send any interested parties a forward of Gerard Tromp's email. I hope to have tmpfs information in the next edition of the FAQ. Of course, buying more RAM will increase your speed. I've heard that increasing RAM from 16 to 32 megs will result in a large increase in speed. Increasing RAM from 32-64 megs will result in a significant increase. Increasing beyond 64megs is not particulairly helpful. Note that this data is anecdotal in nature (I haven't seen it myself), but it makes intuitive sense to me. If someone sends me some SIMMS for our sparcII, I'll be glad to test it out :-) A professor has offered to let me run a fastlink benchmark on his sparc10 with 128megs RAM. I'll post results as soon as they come in. note: I run on a sun sparcII. I'd like to hear data from people on other platforms. I'd especially like to hear data on the speed-RAM relationship. I set up 300 megs of paging space on my workstation, but now I'm running out of hard-drive space. Is there any way I can use my hard drive space more effeciently? [rootd;29may94] Paging space is hard-drive space which is used as virtual RAM. Unix boxes use paging space constantly, swapping processes out to the hard-drive and into RAM constant. Remember that "paging space" is the same as "swap space". There are two types of paging-space on sun systems (and many other types of Unix systems as well): paging files, and paging partitions. Paging files are actual files (you can do an ls and find them in a directory somewhere) in the filesystem. Paging partitions are separate disk partitions, and as such are not in the filesystem. A filesystem has two types of overhead. Consider the following output: bigbox% df Filesystem kbytes used avail capacity Mounted on /dev/sd0a 7735 5471 1491 79% / /dev/sd0g 151399 127193 9067 93% /usr /dev/sd3a 306418 266644 9133 97% /usr2 bigbox% df -i Filesystem iused ifree %iused Mounted on /dev/sd0a 951 3913 20% / /dev/sd0g 10218 66390 13% /usr /dev/sd3a 6278 150394 4% /usr2 The top df command shows the space available on "bigbox" in k. Note that, although sd3a has 306 megs, of which 267 megs are used, only 9 megs are available. This is because the filesystem saves a "10%" rainy day fund, so 10% of the filesystem is unusable. Although you can reduce this percentage (with the root password and using an arcane command), it is not recommended. According to sun's documentation, when the filesystem gets more than 90% full the speed of the filesystem will begin to rapidly drop. When you have a 100 meg paging file, there is a corresponding 10 megs of "rainy-day-fund" which you cannot access, so setting up a 100 meg paging file requires 110 megs of disk space. But when you use a seperate partition as a paging partition, no 10% rainy-day fund is necessary. 100 megs of raw disk space will give you 100 megs of virtual-RAM. The bottom df command shows the number of inodes available in the filesystem. An inode points to files, and is part of the filesystem that you rarely need to look at. By default, when you create a filesystem in a partition, one inode is created for every 2k in the partition. The 306 meg partition has 156,000 inodes, but only 4% of them are used. I don't know how large an inode is (a quick search through my documentation failed to find it) but I would guess that an inode is 256 bytes. If that's true, the 150,000 unused inodes above are wasting 37.5 megs of disk-space. One inode for every 2k is too much. When you create a 100 meg paging file, you only use 1 inode, but that 100 megs of filesystem has a corresponding 50,000 inodes! If you create a paging-partition, you are not using a filesystem, so no inodes are necessary. In addition, when you create a filesystem, you can reduce the number of inodes to something more reasonable (like one inode for every 10k of disk space). I generally don't mess with the inode count on my / and /usr partitions, since that contains the operating system. Make certain not to reduce the default inode number too much: YOU DONT WANT TO RUN OUT OF INODES. We converted our 350 megs of paging files to paging partition, and got another 70 megs of free disk space as a result (20%)! But I don't know how to do all this optimization, and my research assistant is spending all his/her time trying to figure it out. [rootd;21may94] Unix system administration is a complex task which requires experience. An experienced sysadmin can do in minutes what it would take you hours (or days) to accomplish. In addition, an experienced sysadmin won't make stupid mistakes very often (lets see, while I was learning on-the-job I ruined our backup tape during an upgrade {luckily the upgrade was successful!}, moved a directory inside itself as root, botched email service a couple times, and spent tons of time figuring out how to accomplish simple tasks). Most universities have small budgets for their system administrators. Many head sysadmins have recruited students to assist them. Basically the students slave away for nothing, learn tons of stuff, barely pass their classes, become unix gods, and get hired for 40k+/year if/when they graduate/flunk out. If your university has a sysadmin group like this, you can probably "hire" them to support your machine for about $6/hour at about 4 hours/week*machine. The head-sysadmin will be happy to give some money to their more-experienced volunteers, the volunteers get another line on their resume+additional experience, and you get experienced sysadmins to run your machine. In addition, most sysadmin groups have an automated nightly backup. Just think: your machine gets backed up EVERY NIGHT AUTOMATICALLY! At Portland State University the Electrical Engineering sysadmin group has been hired to maintain the unix machines of four other departments, at an average price of $15/week*machine (no additional price for xterms!) The quality of the service is excellent (especially since the most experienced volunteers are usually the ones given the money), there is no annual training-gap as people leave (since the experienced volunteers are constantly training the new ones) and you have the entire resources and experience of the sysadmin group to help you. Of course, test them by deleting an unimportant file and seeing if they can restore it from backups (the backup test is the most important in system administration--have you tested your backups lately?). If they successfully restore the file from backups, give them the sun-optimization list (above two questions) and watch as the most experienced volunteer turns the optimization into a recruit-training session :-) They may even have a contest to see how small they can make your kernel-configuration file! If your location doesn't have such a group, perhaps another universtiy in town has one. How can I identify how much paging space is available on my workstation? [gerard tromp; 29apr94] Paging space, also referred to as swap space, as well as its use can be identified by: pstat -s (Non-root users need to use: /usr/etc/pstat -s) e.g. > sanger 1% /usr/etc/pstat -s > 11456k allocated + 3108k reserved = 14564k used, 252744k available > sanger 2% swap space can be mounted on several disk partitions, that is on several partitions on the same disk or on a partition on several disks. e.g. > sanger 2% cat /etc/fstab > /dev/sd0a / 4.2 rw 1 1 > /dev/sd0e /usr 4.2 rw 1 2 > . > ... several other partitions removed from listing > . > /dev/sd1b swap swap rw 0 0 > /dev/sd2b swap swap rw 0 0 > swap /tmp tmp rw 0 0 > sanger 3% FILE FORMATS How do I convert between crimap and linkage formts? [rootd;29may94] The crimap utilities package contains genlink and linkgen, which converts between .gen files and linkage file. I am attempting to find an ftp site. If you know of one, let me know. I already have source. If I could find the authors, to have them authorize it, I'd be happy to put the entire crimap-utilities package on one of my ftp sites. How do I get my ceph data into crimap format? [rootd;29may94] You can output the file in linkage format, and use link2gen (if you have it, see F2). The disadvantage here is that your marker names are seperated from your data, and its easy to make a mistake and get them mixed up. You can output the file in ped.out format and use mkcrigen. mkcrigen is a great program, which automatically transfers the marker-names with the data (eliminating one source of error). Unfortunately, I only have an executable with a hardcoded 80-marker maximum. Nobody can find the source code. lnktocri is very similar to link2gen, and is included in the multimap tar file John Attwood has a ceph2cri program, which reads your ped.out file and outputs a .gen file. It is available via anonymous ftp from ftp.gene.ucl.ac.uk in /pub/packages/linkage_utils. It runs on DOS machines. According to John Attwood: "Making the Unix-based system available is much more complex, as it involves many scripts, Makefiles and executables, but I'll try to do it when I have time." If you need the unix version, send me email and I'll forward a summary to John Attwood. That way he won't waste time putting together a unix version unless there is definitive interest. Educational resources for teaching genetics Genetics Construction Kit--fly genetics simulator [meir;10Aug94] There is an excellent program called Genetics Construction Kit that models fruit fly genetics - lots of features, and a pretty good interface. It comes on a CD with a bunch of other really good biology education software from a consortium called BioQuest ($89 for the CD, and its really worth it - only mac stuff though). Look around on bulletin boards for the Intro to BioQuest hypercard stack which gives their philosophy and a description of the programs they have. Michael Bacon says: Well, recently out of a genetics class, I can recommend a program called "Catlab." The idea is that you breed lots and lots of cats, and try to figure out what genes control the cat's coat and tail. gen5ajt says: We use Populus 3.x for DOS (Windows version out soonish), this is an excelent population genetics package, I couldn't recommend it too much. It's free and downloadable by ftp from somwhere. FAQ keeper: Darrell Root rootd@ee.pdx.edu or rootd@ohsu.edu HTML by Tim Trautmann timt@ee.pdx.edu From owner-gene-linkage@net.bio.net Wed Nov 23 22:00:00 1994 Path: biosci!bloom-beacon.mit.edu!gatech!news-feed-1.peachnet.edu!usenet.eel.ufl.edu!usenet.cis.ufl.edu!caen!msuinfo!netnews.upenn.edu!sanger.bcm.tju.edu!tromp From: tromp@sanger.bcm.tju.edu (Gerard Tromp) Newsgroups: bionet.molbio.gene-linkage Subject: Re: Pentium chips have f.p.u. error -- rounding error on division Date: 24 Nov 1994 23:26:44 GMT Organization: Biochemistry Lines: 17 Distribution: world Message-ID: <3b37fk$4he@netnews.upenn.edu> References: <3b31b9$4he@netnews.upenn.edu> NNTP-Posting-Host: sanger.bcm.tju.edu Keywords: Intel, Pentium, f.p.u error Greetings, Aljandro Schaffer (developer/co-developer of FASTLINK) informs me that LINKAGE/FASTLINK, fortunately use almost no floating point division. So, the bug is unlikely to affect linkage calculations after all. -- Gerard Tromp, Ph.D. Research Assistant Professor Vox: 215-955-4487 Department of Biochemistry 215-955-4488 and Molecular Biology Fax: 215-955-5393 Thomas Jefferson University 233 South Tenth Street, Room 328 E-mail: tromp@sanger.bcm.tju.edu Philadelphia, PA 19107 U.S.A. From owner-gene-linkage@net.bio.net Wed Nov 23 22:00:00 1994 Path: biosci!agate!howland.reston.ans.net!sol.ctr.columbia.edu!caen!msuinfo!netnews.upenn.edu!sanger.bcm.tju.edu!tromp From: tromp@sanger.bcm.tju.edu (Gerard Tromp) Newsgroups: bionet.molbio.gene-linkage Subject: Pentium chips have f.p.u. error -- rounding error on division Date: 24 Nov 1994 21:42:01 GMT Organization: Biochemistry Lines: 31 Distribution: world Message-ID: <3b31b9$4he@netnews.upenn.edu> NNTP-Posting-Host: sanger.bcm.tju.edu Keywords: Intel, Pentium, f.p.u error Greetings fellow linkage people, November 24, 1994. In today's New York Times financial section an article appeared indicating that Intel Pentium chips had an error in the floating point unit (f.p.u.). The error caused rounding of numbers during some division steps such that only 5 instead of 16 significant numbers were accurate. This potentially presents a serious problem for the types of computation necessary for linkage analysis. Intel has known about the error since June, and have now started manufacturing corrected Pentium chips. Intel made some lame statement that it would affect average users only 9 times in a billion. The basis for such probability statement is unclear. _HOWEVER_ they also indicated that they would be willing to "work with scientists and engineers if their applications were likely to be affected". The full implication of the statement is unclear -- presumably one can obtain a corrected chip if it is evident that one's results are likely to be affected i.e. wrong. Just thought everyone should be aware of the potential problem. Perhaps this is the source of some of the recent inconsistancies on DOS machines. -- Gerard Tromp, Ph.D. Research Assistant Professor Vox: 215-955-4487 Department of Biochemistry 215-955-4488 and Molecular Biology Fax: 215-955-5393 Thomas Jefferson University 233 South Tenth Street, Room 328 E-mail: tromp@sanger.bcm.tju.edu Philadelphia, PA 19107 U.S.A. From owner-gene-linkage@net.bio.net Thu Nov 24 22:00:00 1994 Path: biosci!agate!howland.reston.ans.net!pipex!sunsite.doc.ic.ac.uk!daresbury!hgmp.mrc.ac.uk!ifenton From: ifenton@hgmp.mrc.ac.uk (I. Fenton) Newsgroups: bionet.molbio.gene-linkage Subject: Re: Pentium chips have f.p.u. error -- rounding error on division Date: 25 Nov 1994 13:08:31 GMT Organization: MRC Human Genome Resource Centre Lines: 22 Message-ID: <3b4nkf$n15@mercury.hgmp.mrc.ac.uk> References: <3b31b9$4he@netnews.upenn.edu> NNTP-Posting-Host: tin.hgmp.mrc.ac.uk Keywords: Intel, Pentium, f.p.u error as regards the pentium bug, my recent problems on this group have been with a 486 pc, however i have ordered a pentium pc, and the manufacturer says that it is intel's problem, and are not willing to replace any defective cpu. soooo, my question is :- does linkage or fastlink use this particular "FDIV" hardware double- precision divide routine which is - apparently - the source of the trouble ? can we tell if linkage/fastlink actually issue these instructions? i need to know - we already have one pentium pc here dedicated to doing linkage problems, and i have found it's pentium chip to be a buggy one. quote of the year - when i called intel, they said : "it's not a bug, it's an issue" har bleedin' har. Iain Fenton, Cardiff, UK. From owner-gene-linkage@net.bio.net Thu Nov 24 22:00:00 1994 Path: biosci!agate!news.Stanford.EDU!stout.Stanford.EDU!cherry From: cherry@stout.Stanford.EDU (Mike Cherry) Newsgroups: bionet.molbio.gene-linkage Subject: Re: Pentium chips have f.p.u. error -- rounding error on division Date: 25 Nov 1994 14:05:39 GMT Organization: Stanford University Genetics Department Lines: 53 Message-ID: <3b4qvj$gp5@nntp.Stanford.EDU> References: <3b31b9$4he@netnews.upenn.edu> <3b4nkf$n15@mercury.hgmp.mrc.ac.uk> NNTP-Posting-Host: stout.stanford.edu Keywords: Intel, Pentium, f.p.u error The following message on the Risks Forum might be of interest to those concerned withthe Pentium bug (issue). Mike > RISKS-LIST: RISKS-FORUM Digest Tuesday 22 November 1994 Volume 16 : Issue 57 > > FORUM ON RISKS TO THE PUBLIC IN COMPUTERS AND RELATED SYSTEMS > ACM Committee on Computers and Public Policy, Peter G. Neumann, moderator > > ***** See last item for information on RISKS (comp.risks), disclaimers ***** > > ... > > Date: Mon, 21 Nov 1994 15:20:58 -0800 (PST) > From: broadley@turing.ucdavis.edu (Bill Broadley) > Subject: Pentium FDIV bug > > As this below tiny program from Thomas Koenig demonstrates the pentium > sometimes only returns single precision when dividing floating point doubles. > > #include > int main() > { double x,y,z; > x = 4195835.0; y = 3145727.0; > z = x - (x / y) * y; > printf("%f\n",z); > return 0; > } > > It will return 256 if you have the fdiv bug, and zero if you don't. > > I've written 3 similar programs: > 1 like the above, but more resistent to compiler optimization > 1 that searches randomly for the bug (no special seeds) > 1 that searches linearly for the bug. > > I'll leave it to the reader to interpret the risks of a cpu that > silently returns 1/2 the precision that you expect. > > BTW in my test it happens about about 1 in 10^9 divisions or about > once every 21 minutes with a sequential search. I.e. if your running > flat out divisions and multiplies (to check the divs). > > It can be MUCH higher, up to once a second, with biased random numbers. > > I'll make havebug.c rndsearchbug.c and linsearchbug.c available > for anonymous ftp at math.ucdavis.edu > > For further references read comp.sys.intel under the fdiv bug thread. > > Bill Broadley, UCD Math Sys-Admin Broadley@math.ucdavis.edu > http://ucdmath.ucdavis.edu/~broadley From owner-gene-linkage@net.bio.net Mon Nov 28 22:00:00 1994 Path: biosci!ns1.faseb.org!darwin.sura.net!news.lsu.edu!unix1.sncc.lsu.edu!LSUVAX.SNCC.LSU.EDU!JCOLE From: jcole@LSUVAX.SNCC.LSU.EDU (i love my VAX!) Newsgroups: bionet.molbio.gene-linkage Subject: Re: Pentium chips have f.p.u. error -- rounding error on division Date: 28 Nov 1994 16:04:00 GMT Organization: LSU System Network Computer Center Lines: 29 Distribution: world Message-ID: <3bcv1g$1r34@unix1.sncc.lsu.edu> References: <3b31b9$4he@netnews.upenn.edu> Reply-To: jcole@LSUVAX.SNCC.LSU.EDU NNTP-Posting-Host: sn01.sncc.lsu.edu In article <3b31b9$4he@netnews.upenn.edu>, tromp@sanger.bcm.tju.edu (Gerard Tromp) writes > Intel made some lame statement that it would affect average users only 9 >times in a billion. The basis for such probability statement is unclear. _HOWEVER_ >they also indicated that they would be willing to "work with scientists and >engineers if their applications were likely to be affected". The full implication >of the statement is unclear -- presumably one can obtain a corrected chip if it >is evident that one's results are likely... > Just thought everyone should be aware of the potential problem. Perhaps >this is the source of some of the recent inconsistancies on DOS machines. First, sorry about the annoying format...I am just getting used to this editor. Anyway, I am a dedicated IBM user only when I can not get my hands on a DEC APX-series machine. Let's face it, Intel has demonstrated once again their slipshod approach to engineering and pseudo-foxes. I realize the Alpha machines cost a lot more, but maybe you get what you pay for...90 mHz with errors in the important stuff (how do you miss such a significant thing as a buggy fpu?!), or >200 mHz (with BIG buses!) and real engineering. Sorry to ramble...I am kinda fond of the guys at DEC... John B. Cole Graduate Research Assistant Department of Dairy Science Louisiana State University Baton Rpuge, LA 70803 (504)388-4411 (all opinions herein are mine in their entirety, not LSU's...}:) ) From owner-gene-linkage@net.bio.net Tue Nov 29 22:00:00 1994 Newsgroups: bionet.molbio.gene-linkage Path: biosci!bloom-beacon.mit.edu!panix!zip.eecs.umich.edu!umn.edu!lenti.med.umn.edu!dean From: dean@lenti.med.umn.edu (Dean Flanders) Subject: Pentium chips f.p.u. error 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, 30 Nov 1994 06:44:44 GMT Lines: 133 This is FYI, I am not taking sides on this issue, but note offer at the end. ----- Forwarded message begins here ----- From: Jay Rothman Xref: news1.cis.umn.edu comp.sys.intel:21645 Date: 27 Nov 1994 14:45:47 -0700 Subject: *** The President of Intel responds... Newsgroups: comp.sys.intel Subject: My Perspective on Pentium - AGS Date: 27 Nov 1994 19:31:21 GMT Organization: Netcom Lines: 102 Distribution: world Message-ID: <3bamq9$avt@ixnews1.ix.netcom.com> NNTP-Posting-Host: ix-pa3-16.ix.netcom.com Andy Grove has asked me to post the following for him. Since it is the weekend and we are out of the office, I am posting from my home system. Richard Wirt Director SW Technology Intel Corp This is Andy Grove, president of Intel. I'd like to comment a bit on the conversations that have been taking place here. First of all, I am truly sorry for the anxiety created among you by our floating point issue. I read thru some of the postings and it's clear that many of you have done a lot of work around it and that some of you are very angry at us. Let me give you my perspective on what has happened here. The Pentium processor was introduced into the market in May of '93 after the most extensive testing program we at Intel have ever embarked on. Because this chip is three times as complex as the 486, and because it includes a number of improved floating point algorithms, we geared up to do an array of tests, validation, and verification that far exceeded anything we had ever done. So did many of our OEM customers. We held the introduction of the chip several months in order to give them more time to check out the chip and their systems. We worked extensively with many software companies to this end as well. We were very pleased with the result. We ramped the processor faster than any other in our history and encountered no significant problems in the user community. Not that the chip was perfect; no chip ever is. From time to time, we gathered up what problems we found and put into production a new "stepping" -- a new set of masks that incorporated whatever we corrected. Stepping N was better than stepping N minus 1, which was better than stepping N minus 2. After almost 25 years in the microprocessor business, I have come to the the conclusion that no microprocessor is ever perfect; they just come closer to perfection with each stepping. In the life of a typical microprocessor, we go thru half a dozen or more such steppings. Then, in the summer of '94, in the process of further testing (which continued thru all this time and continues today), we came upon the floating point error. We were puzzled as to why neither we nor anyone else had encountered this earlier. We started a separate project, including mathematicians and scientists who work for us in areas other than the Pentium processor group to examine the nature of the problem and its impact. This group concluded after months of work that (1) an error is only likely to occur at a frequency of the order of once in nine billion random floating point divides, and that (2) this many divides in all the programs they evaluated (which included many scientific programs) would require elapsed times of use that would be longer than the mean time to failure of the physical computer subsystems. In other words, the error rate a user might see due to the floating point problem would be swamped by other known computer failure mechanisms. This explained why nobody -- not us, not our OEM customers, not the software vendors we worked with and not the many individual users -- had run into it. As some of you may recall, we had encountered thornier problems with early versions of the 386 and 486, so we breathed a sigh of relief that with the Pentium processor we had found what turned out to be a problem of far lesser magnitude. We then incorporated the fix into the next stepping of both the 60 and 66 and the 75/90/100 MHz Pentium processor along with whatever else we were correcting in that next stepping. Then, last month Professor Nicely posted his observations about this problem and the hubbub started. Interestingly, I understand from press reports that Prof. Nicely was attempting to show that Pentium-based computers can do the jobs of big time supercomputers in numbers analyses. Many of you who posted comments are evidently also involved in pretty heavy duty mathematical work. That gets us to the present time and what we do about all this. We would like to find all users of the Pentium processor who are engaged in work involving heavy duty scientific/floating point calculations and resolve their problem in the most appropriate fashion including, if necessary, by replacing their chips with new ones. We don't know how to set precise rules on this so we decided to do it thru individual discussions between each of you and a technically trained Intel person. We set up 800# lines for that purpose. It is going to take us time to work thru the calls we are getting, but we will work thru them. I would like to ask for your patience here. Meanwhile, please don't be concerned that the passing of time will deprive you of the opportunity to get your problem resolved -- we will stand behind these chips for the life of your computer. Sorry to be so long-winded -- and again please accept my apologies for the situation. We appreciate your interest in the Pentium processor, and we remain dedicated to bringing it as close to perfection as possible. I will monitor your communications in the future -- forgive me if I can't answer each of you individually. Andy Grove ========================================================================= Division of Genetics and Metabolism I University of Minnesota I Box 485 UMHC I "If all you have is a hammer, Harvard Street at East River Road I you tend to look at every Minneapolis, MN 55455 I problem as a nail." I Voice (612) 625-5628 I -Maslow Fax (612) 624-6645 I Email dean@gene.med.umn.edu I ========================================================================== From owner-gene-linkage@net.bio.net Tue Nov 29 22:00:00 1994 Path: biosci!bloom-beacon.mit.edu!gatech!swrinde!pipex!uunet!jabba.fdn.org!jussieu.fr!univ-lyon1.fr!serra.unipi.it!sirio.cineca.it!eagle!villa From: villa@eagle.bio.unipr.it (Ferdinando Villa) Newsgroups: bionet.molbio.gene-linkage Subject: HELP - Ethidium Bromide contamination Date: 30 Nov 1994 15:46:59 GMT Organization: Cineca Lines: 27 Message-ID: <3bi6pj$ofj@sirio.cineca.it> NNTP-Posting-Host: eagle.bio.unipr.it X-Newsreader: TIN [version 1.2 PL0] Hello, I need urgent advice. A friend working in our lab got contaminated with diluted (1ml in 1l water) ethidium bromide (a single finger got wet with the solution, because of a hole in the glove). She washed her hands after a minute or so, when she realized the problem, with water and soap. No trace of remaining ethidium was shown under UV light on her finger. We need to know urgently which controls she should carry out after that. The security instruction refer to the following book: Sambrook et al, "Molecular Cloning, A Lab Manual", Cold Spring Harbor labs 1989. As we don't own the book and would take some time ordering it, we would be most grateful to anyone who cares to give any advice on what to do. With best wishes and thanks in advance, Ferdinando Villa -- Ferdinando Villa, Ph.D. Institute of Ecology Direct phone: +39-521-905615 University of Parma FAX: +39-521-905402 Viale delle Scienze Home phone (voice mail): +39-521-604013 43100 Parma, Italy e.mail: villa@eagle.bio.unipr.it From owner-gene-linkage@net.bio.net Wed Nov 30 22:00:00 1994 Path: biosci!rutgers!uwm.edu!vixen.cso.uiuc.edu!howland.reston.ans.net!torn!mcshub!informer1.cis.McMaster.CA!muss.cis.McMaster.CA!not-for-mail From: u9317302@muss.cis.McMaster.CA (R. Wong) Newsgroups: bionet.molbio.gene-linkage Subject: What is the method to finding identifying a chromosome location? Date: 1 Dec 1994 00:06:33 -0500 Organization: McMaster University, Hamilton, Ontario, Canada. Lines: 15 Message-ID: <3bjlkp$pq7@muss.cis.McMaster.CA> NNTP-Posting-Host: muss.cis.mcmaster.ca I have a genetics project that I am working on and I am in a little bit of a rut. I am supposed to: Outline a procedure to determine the chromosome location of a particular gene. (eg. a process by which to discover that chromosome #11 is the location for human B-globin) Can anyone out there in internet land help me out? P.S. What would be even better is if anyone could name an article and in what journal where I could find an example of a procedure that has actually been done. (It doesn't have to human chromosomes.) Thanks a lot. Rob. From owner-gene-linkage@net.bio.net Wed Nov 30 22:00:00 1994 Path: biosci!OCELOT.RUTGERS.EDU!price From: price@OCELOT.RUTGERS.EDU ("Price, Carl A") Newsgroups: bionet.molbio.gene-linkage Subject: Position available Date: 1 Dec 1994 12:53:19 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 44 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net POSITION AVAILABLE Associate Director, Center for Sequenced Plant Genes Administers the Registry for Sequenced Plant Genes, which serves as a repository for designations of sequenced plant genes as recommended by the Commission on Plant Gene Nomenclature (CPGN). Interprets and advises scientific community on the interpretation and applications of CPGN guidelines. Identifies and recruits international scientific authorities to serve as group leaders for the review of proposed gene designations by the CPGN. Organizes reviews and examines all proposals for consistency with guidelines. Manages the electronic communication of approved designations into the National Agricultural Library and other public databases. Communicates with editors-in-chief and reviews their adherence to adherence to CPGN's recommendations. Organizes workshops on gene nomenclature at international meetings. Advises industrial clients on the potential applications of newly sequenced plant genes and their relevance to companies' objectives. Requires an advanced degree in molecular biology or related field, plus extensive experience in plant molecular biology. Experience must include: construction of DNA libraries, database management, international scientific activities and journal editing. Familiarity with sequenced plant genes to include the recognition of genes associated with nuclear, chloroplast and mitochondrial genomes are also required. Excellent written and oral communication, as well as interpersonal skills are essential. Position offers competitive salary and a comprehensive benefits program including tuition remission for employees and their children. Please send resume, including Ref#137 to: Robell@personnel.rutgers.edu or by ordinary mail to: Rutgers, The State University of NJ Division of Personnel Services Attn: Sonia Robell, Piscataway, NJ 08855, USA Rutgers is an Affirmative Action/Equal Employment Opportunity Employer, M/F. Employment eligibility verification required.