From owner-gene-linkage@net.bio.net Sun Jun 02 23:00:00 1996 Path: biosci!bcm.tmc.edu!pendragon!news.msfc.nasa.gov!elroy.jpl.nasa.gov!lll-winken.llnl.gov!fnnews.fnal.gov!unixhub!news.Stanford.EDU!not-for-mail From: ladasky@leland.Stanford.EDU (John Ladasky) Newsgroups: bionet.molbio.ageing,bionet.molbio.bio-matrix,bionet.molbio.evolution,bionet.molbio.gene-linkage,bionet.molbio.gene-org,bionet.molbio.methds-reagnts Subject: Re: DNA ligation help Followup-To: bionet.molbio.methds-reagnts Date: 3 Jun 1996 10:47:29 -0700 Organization: Stanford University, CA 94305, USA Lines: 23 Message-ID: <4ov8fh$7gm@elaine35.Stanford.EDU> References: <4opneu$nke@newz.oit.unc.edu> NNTP-Posting-Host: elaine35.stanford.edu Xref: biosci bionet.molbio.ageing:2745 bionet.molbio.bio-matrix:733 bionet.molbio.evolution:4577 bionet.molbio.gene-linkage:1081 bionet.molbio.methds-reagnts:45260 Followups have been limited to bionet.molbio.methds-reagnts. In article <4opneu$nke@newz.oit.unc.edu>, chunlin xin wrote: >Hi, there, I have trouble in DNA ligation, the case below: > Insert Fragment: 16.3kb SalI Frag. > Vector: Bscrip-KS(-) SalI cut plasmid or other > salI cut expression vector > It looks like no ligation problem, but in fact, I cannot >success to ligate them and transfer them into DH5a no matter I use >chemical or electroparation method, Have anybody ever meet the same problem? >How can I solve them? Any suggestion is appreciated! Thanks for you attention! A 16.3 Kb insertion is quite large. DH5-alpha, and most other normal strains of E. coli, cannot reliably maintain plasmids larger than 10 Kb. (I'm not sure why this is so.) So your ligation and transformation may both be successful, but then you are not getting any ampicillin-resistant colonies. Can you subclone this fragment? -- Unique ID : Ladasky, John Joseph Jr. Title : BA Biochemistry, U.C. Berkeley, 1989 (Ph.D. perhaps 1998???) Location : Stanford University, Dept. of Structural Biology, Fairchild D-105 Keywords : immunology, music, running, Green From owner-gene-linkage@net.bio.net Sun Jun 02 23:00:00 1996 Newsgroups: bionet.molbio.ageing,bionet.molbio.bio-matrix,bionet.molbio.evolution,bionet.molbio.gene-linkage,bionet.molbio.gene-org,bionet.molbio.methds-reagnts Path: biosci!daresbury!yama.mcc.ac.uk!bofh.dot!thor.cf.ac.uk!news From: Nick Jacobsen Subject: Re: DNA ligation help Sender: news@cf.ac.uk (USENET News System) Message-ID: Date: Mon, 3 Jun 1996 09:21:04 GMT To: xcl@med.unc.edu X-Nntp-Posting-Host: d053.mg.cf.ac.uk Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset=us-ascii References: <4opneu$nke@newz.oit.unc.edu> Mime-Version: 1.0 X-Mailer: Mozilla 1.22 (Windows; I; 16bit) Organization: Institute of Medical Genetics Cardiff Lines: 14 Xref: biosci bionet.molbio.ageing:2744 bionet.molbio.bio-matrix:732 bionet.molbio.evolution:4576 bionet.molbio.gene-linkage:1080 bionet.molbio.methds-reagnts:45236 Hi, I find that the majority of problems with DNA ligation inefficiency are due to ATP degradation in the reaction buffer. If in doubt order new buffer and freeze in small aliquots. You can also order Pharmacia ligase - you have to order separate 10mM ATP with it to add to the reaction as required. You have to be fairly accurate with the amount of ATP added as too much is as bad as too little. I hope this is of help to you cheers Nick Jacobsen. From owner-gene-linkage@net.bio.net Sun Jun 02 23:00:00 1996 Newsgroups: bionet.molbio.ageing,bionet.molbio.bio-matrix,bionet.molbio.evolution,bionet.molbio.gene-linkage,bionet.molbio.gene-org,bionet.molbio.methds-reagnts Path: biosci!daresbury!yama.mcc.ac.uk!bofh.dot!thor.cf.ac.uk!news From: Nick Jacobsen Subject: Re: DNA ligation help Sender: news@cf.ac.uk (USENET News System) Message-ID: Date: Mon, 3 Jun 1996 09:20:58 GMT To: xcl@med.unc.edu X-Nntp-Posting-Host: d053.mg.cf.ac.uk Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset=us-ascii References: <4opneu$nke@newz.oit.unc.edu> Mime-Version: 1.0 X-Mailer: Mozilla 1.22 (Windows; I; 16bit) Organization: Institute of Medical Genetics Cardiff Lines: 14 Xref: biosci bionet.molbio.ageing:2743 bionet.molbio.bio-matrix:731 bionet.molbio.evolution:4575 bionet.molbio.gene-linkage:1079 bionet.molbio.methds-reagnts:45235 Hi, I find that the majority of problems with DNA ligation inefficiency are due to ATP degradation in the reaction buffer. If in doubt order new buffer and freeze in small aliquots. You can also order Pharmacia ligase - you have to order separate 10mM ATP with it to add to the reaction as required. You have to be fairly accurate with the amount of ATP added as too much is as bad as too little. I hope this is of help to you cheers Nick Jacobsen. From owner-gene-linkage@net.bio.net Sun Jun 02 23:00:00 1996 Newsgroups: bionet.molbio.ageing,bionet.molbio.bio-matrix,bionet.molbio.evolution,bionet.molbio.gene-linkage,bionet.molbio.gene-org,bionet.molbio.methds-reagnts Path: biosci!daresbury!yama.mcc.ac.uk!bofh.dot!thor.cf.ac.uk!news From: Nick Jacobsen Subject: Re: DNA ligation help Sender: news@cf.ac.uk (USENET News System) Message-ID: Date: Mon, 3 Jun 1996 09:20:40 GMT To: xcl@med.unc.edu X-Nntp-Posting-Host: d053.mg.cf.ac.uk Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset=us-ascii References: <4opneu$nke@newz.oit.unc.edu> Mime-Version: 1.0 X-Mailer: Mozilla 1.22 (Windows; I; 16bit) Organization: Institute of Medical Genetics Cardiff Lines: 14 Xref: biosci bionet.molbio.ageing:2742 bionet.molbio.bio-matrix:730 bionet.molbio.evolution:4574 bionet.molbio.gene-linkage:1078 bionet.molbio.methds-reagnts:45234 Hi, I find that the majority of problems with DNA ligation inefficiency are due to ATP degradation in the reaction buffer. If in doubt order new buffer and freeze in small aliquots. You can also order Pharmacia ligase - you have to order separate 10mM ATP with it to add to the reaction as required. You have to be fairly accurate with the amount of ATP added as too much is as bad as too little. I hope this is of help to you cheers Nick Jacobsen. From owner-gene-linkage@net.bio.net Sun Jun 02 23:00:00 1996 Newsgroups: bionet.molbio.ageing,bionet.molbio.bio-matrix,bionet.molbio.evolution,bionet.molbio.gene-linkage,bionet.molbio.gene-org,bionet.molbio.methds-reagnts Path: biosci!daresbury!yama.mcc.ac.uk!bofh.dot!thor.cf.ac.uk!news From: Nick Jacobsen Subject: Re: DNA ligation help Sender: news@cf.ac.uk (USENET News System) Message-ID: Date: Mon, 3 Jun 1996 09:20:12 GMT To: xcl@med.unc.edu X-Nntp-Posting-Host: d053.mg.cf.ac.uk Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset=us-ascii References: <4opneu$nke@newz.oit.unc.edu> Mime-Version: 1.0 X-Mailer: Mozilla 1.22 (Windows; I; 16bit) Organization: Institute of Medical Genetics Cardiff Lines: 14 Xref: biosci bionet.molbio.ageing:2741 bionet.molbio.bio-matrix:729 bionet.molbio.evolution:4573 bionet.molbio.gene-linkage:1077 bionet.molbio.methds-reagnts:45233 Hi, I find that the majority of problems with DNA ligation inefficiency are due to ATP degradation in the reaction buffer. If in doubt order new buffer and freeze in small aliquots. You can also order Pharmacia ligase - you have to order separate 10mM ATP with it to add to the reaction as required. You have to be fairly accurate with the amount of ATP added as too much is as bad as too little. I hope this is of help to you cheers Nick Jacobsen. From owner-gene-linkage@net.bio.net Sun Jun 02 23:00:00 1996 Newsgroups: bionet.molbio.ageing,bionet.molbio.bio-matrix,bionet.molbio.evolution,bionet.molbio.gene-linkage,bionet.molbio.gene-org,bionet.molbio.methds-reagnts Path: biosci!daresbury!yama.mcc.ac.uk!bofh.dot!thor.cf.ac.uk!news From: Nick Jacobsen Subject: Re: DNA ligation help Sender: news@cf.ac.uk (USENET News System) Message-ID: Date: Mon, 3 Jun 1996 09:19:49 GMT To: xcl@med.unc.edu X-Nntp-Posting-Host: d053.mg.cf.ac.uk Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset=us-ascii References: <4opneu$nke@newz.oit.unc.edu> Mime-Version: 1.0 X-Mailer: Mozilla 1.22 (Windows; I; 16bit) Organization: Institute of Medical Genetics Cardiff Lines: 14 Xref: biosci bionet.molbio.ageing:2740 bionet.molbio.bio-matrix:728 bionet.molbio.evolution:4572 bionet.molbio.gene-linkage:1076 bionet.molbio.methds-reagnts:45232 Hi, I find that the majority of problems with DNA ligation inefficiency are due to ATP degradation in the reaction buffer. If in doubt order new buffer and freeze in small aliquots. You can also order Pharmacia ligase - you have to order separate 10mM ATP with it to add to the reaction as required. You have to be fairly accurate with the amount of ATP added as too much is as bad as too little. I hope this is of help to you cheers Nick Jacobsen. From owner-gene-linkage@net.bio.net Sun Jun 02 23:00:00 1996 Path: biosci!bcm.tmc.edu!cs.utexas.edu!chi-news.cic.net!news.compuserve.com!news.production.compuserve.com!news From: Survey Administration <74750.1341@CompuServe.COM> Newsgroups: bionet.microbiology,bionet.molbio.ageing,bionet.molbio.evolution,bionet.molbio.gene-linkage,bionet.molbio.hiv Subject: WE NEED YOUR INPUT Date: 3 Jun 1996 03:18:43 GMT Organization: Kitty Knight Corporation Lines: 25 Message-ID: <4otlij$3ni$5@mhade.production.compuserve.com> Xref: biosci bionet.microbiology:6248 bionet.molbio.ageing:2738 bionet.molbio.evolution:4571 bionet.molbio.gene-linkage:1075 bionet.molbio.hiv:2349 Please excuse this brief intrusion, but we are trying to locate any and all holders of academic degrees conferred within the last ten (10) years. The Kitty Knight Corporation, Boston, MA, is currently searching for qualified individuals to participate in a ***PAID*** study focusing on post-secondary, graduate, and professional education in the United States. Holders of ALL types of degrees in ALL fields of study are needed. We would like to hear from you as long as your degree was earned at an accredited institution in the United States. After an initial screening, qualified participant will be asked to complete a questionaire of approx 150 questions. Everyone who completes the survey will receive a $100 stipend. Naturally, *ALL* information will be held in the strictest confidence. To express interest, please send your name, mailing address, and photocopies of **ALL** degrees you have earned to: The Kitty Knight Corporation, Attn: Study 96-3H, Back Bay Annex, P O Box 546, Boston, MA 02117. (If not obvious from the degree, please indicate the field of study.) Thank You Very Much! From owner-gene-linkage@net.bio.net Mon Jun 03 23:00:00 1996 Path: biosci!rutgers!uwm.edu!vixen.cso.uiuc.edu!newsfeed.internetmci.com!in1.uu.net!01-newsfeed.univie.ac.at!newsfeed.ACO.net!embdec.bcc.univie.ac.at!usenet From: walter@gem.univie.ac.at (Glaser Walter) Newsgroups: bionet.molbio.gene-linkage Subject: Problem with Mapmaker/exp 3.0b Date: 4 Jun 1996 08:29:21 GMT Organization: Vienna University Computing Center Lines: 12 Message-ID: <4p0s51$5bf@embdec.bcc.univie.ac.at> NNTP-Posting-Host: 6105b.bcc.univie.ac.at Mime-Version: 1.0 Content-Type: Text/Plain; charset=US-ASCII X-Newsreader: WinVN 0.99.7 I am using the PC-Version of MAPMAKER/EXP 3.0b. The Program was received by FTP from genome.wi.mit.edu (mapm3pc1.exe mapm3pc2.exe) When the Program starts the 'default linkage critieria' are both set to zero and not to LOD 3.0 and 50cM as stated in the manual. The Program also refuses to change the the values when I try to reset them with 'default linkage criteria 3.0 80'. Thanks in advance Walter Glaser Inst. for Microbiol. and Gentics Vienna Biocenter From owner-gene-linkage@net.bio.net Mon Jun 03 23:00:00 1996 Path: biosci!rutgers!uwm.edu!vixen.cso.uiuc.edu!howland.reston.ans.net!Germany.EU.net!ieunet!web3.tcd.ie!cmegan.gen.tcd.ie!user From: dmachugh@mail.tcd.ie (David MacHugh) Newsgroups: bionet.molbio.gene-linkage Subject: HGMP - current status? Date: Tue, 04 Jun 1996 13:14:09 +0000 Organization: Genetics Department, Trinity College, Dublin 2 Lines: 22 Message-ID: NNTP-Posting-Host: cmegan.gen.tcd.ie Hi, Just a quick query. Does anyone have a rough idea what the current status of the human genome linkage map is. In particular, I would like to know how many type I markers and how many type II markers have been identified and mapped. Thanks in advance, David MacHugh -- ********************************************************************* * (__) David MacHugh PhD, E-mail: dmachugh@mail.tcd.ie * * (@*) Bovine Genetics, Phone: (353)-1-6081088 * * /-------\u' Genetics Department, Fax: (353)-1-6798558 * * / | || Trinity College, * * ||----|| Dublin 2. * * ^^ ^^ Ireland. * ********************************************************************* From owner-gene-linkage@net.bio.net Tue Jun 04 23:00:00 1996 Path: biosci!rutgers!uwm.edu!news.cse.psu.edu!news.cc.swarthmore.edu!netnews.upenn.edu!NewsWatcher!user From: keller@email.chop.edu (Margaret A. Keller, Ph.D.) Newsgroups: bionet.molbio.gene-linkage Subject: Fluorescent Oligo Synthesis Date: Wed, 05 Jun 1996 14:14:48 -0500 Organization: Nucleic Acid/Protein Research Core Facility, The Children's Hospital of Philadelphia Lines: 10 Message-ID: NNTP-Posting-Host: 159.14.43.40 The Nucleic Acid/Protein Research Core Facility at The Children's Hospital of Philadelphia would like to offer linkage researchers a limited time special on the synthesis of fluorescent primers. 40 nm or 200 nm scales are available with either 6-FAM, HEX or TET labels at discounted rates. The per base charge is $0.90/base for 40 nmol and $1.15/b for 200nmol plus $300 per bottle of fluorescent amidite plus $25 per OPC purification. The fluorescent labeling reagent can be used for several oligos over several days. Turnaround time is 7-10 business days. There is a $12 charge for overnight shipping. Please email napcore@email.chop.edu or call (215) 590-3897 for further information. From owner-gene-linkage@net.bio.net Tue Jun 04 23:00:00 1996 Path: biosci!mad.adelaide.edu.au!rwallace From: rwallace@mad.adelaide.edu.au (Robyn Wallace) Newsgroups: bionet.molbio.gene-linkage Subject: Re: HGMP - current status? Date: 4 Jun 1996 20:46:17 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 34 Sender: daemon@net.bio.net Distribution: world Message-ID: <199606050344.NAA09418@pulse.health.adelaide.edu.au> NNTP-Posting-Host: net.bio.net >Hi, > >Just a quick query. Does anyone have a rough idea what the current status >of the human genome linkage map is. In particular, I would like to know >how many type I markers and how many type II markers have been identified >and mapped. > >Thanks in advance, > > >David MacHugh > Genethon have just released their latest (and final) genetic map, consisting of 5,264 microsatellite markers. It can be found in Nature vol 380 (March 1996). ============================================================================ Robyn Wallace Department of Cytogenetics and Molecular Genetics /\_/\ Womens and Childrens Hospital ( o o ) North Adelaide, South Australia 5006 > - < Ph 61 08 204 6442 Fax 61 08 204 7342 Email rwallace@mad.adelaide.edu.au ============================================================================ From owner-gene-linkage@net.bio.net Fri Jun 14 23:00:00 1996 Path: biosci!internet!biosci!not-for-mail From: biohelp (BIOSCI Administrator) Newsgroups: bionet.molbio.gene-linkage Subject: IMPORTANT - BIOSCI Fundraising Update! Date: 15 Jun 1996 02:00:33 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 154 Sender: daemon@net.bio.net Distribution: world Message-ID: <199606150900.CAA26064@net.bio.net> NNTP-Posting-Host: net.bio.net BIOSCI is about halfway to its funding goal!! I'm interrupting the usual monthly posting of the BIOSCI miniFAQ to bring you up to date on BIOSCI fundraising progress, a topic of concern to your future use of this resource. Thank you in advance for taking the time to read this message carefully. Last year we announced that BIOSCI was going to adopt the U.S. Public Broadcasting System model to fund its operations after our DOE/NSF grant runs out later this year. Unlike PBS, we are not soliciting contributions from users; we are only selling ads on our Web pages solely to cover our operating costs. Our goal is to seek sponsorships until we build up an operating reserve of about $100,000 and then cease further promotions until we need to build the reserve back up. (The accountants among our readership will be familiar with the problem of deferred revenue which we can not safely utilize until ads have been displayed for a period of time.) We are only about halfway to our funding goal and need to raise further funds to avoid having to curtail services at net.bio.net. Fundraising is time-consuming, however, and we need your help as explained further below. Our operating costs consist of our network connection, phone lines, hardware maintenance (we will be getting newer and faster hardware soon!), plus 0.7 FTE of salaries covering UNIX systems admin, technical support, quality assurance, i.e., testing, of our system, and administrative costs (such as the time it takes to actually find/write/call potential sponsors and raise money!). Although the BIOSCI staff does get compensated for a portion of the work that they do, this project has always received a lot of free after-hours and "vacation" time labor, so we hope that no one will begrudge the time that we do charge to the project to serve you. All of the three part-time staff members, Dave Mack, Julie Lawrence, and myself, have full time day jobs and families in addition to working hard to keep this service running for all of you. Julie and Dave Mack are subcontractors for BIOSCI; my time that is charged to the project defrays a portion of my regular salary instead of adding to my income. Besides having to relocate the project, we were very busy this last year building new infrastructure such as our WWW hypermail interface to the system. This was released last December along with scores of WAIS indices for the newsgroups. Virtually everything is complete, although we do continue to find and fix bugs (many through your helpful feedback!). We are still having some problems with our WAIS indexing. The archives continue to grow rapidly. We are running over 100 indexes now versus three previously and any systems crashes cause greater havoc with the indexing than before! We are still working to fix this as fast as our resources permit and appreciate your patience, but we have been able to automate a lot of the infrastructure to reduce labor as compared to past requirements. We have also implemented new software to make moderation of BIOSCI/bionet newsgroups much easier and combat the growing problem of Internet junk mail and USENET "spamming." About 20% of our groups are now moderated, many of them by the BIOSCI staff! This, for example, made a major difference last year in the quality of content in our EMPLOYMENT/bionet.jobs.offered newsgroup which many commercial concerns and recruiting firms are using **without charge** to recruit candidates for positions in the biological sciences. We are also now in a position to have sponsors for individual newsgroups as you will have noticed if you have visited http://www.bio.net/ and clicked on "Access the BIOSCI/bionet newsgroups" recently. So, how can you help?? ---------------------- As noted above it can take a lot of time to contact potential sponsors if I have to do it all myself. Our request is quite simple. You can do two important things which will take very little time for you individually. First, please use our WWW system at http://www.bio.net/ to access the archives. You can now post or reply to messages via your Web browser. Your usage helps attract sponsors. If you contact any of our sponsors, please be sure to thank them for supporting BIOSCI. It is critical for them to get this feedback if they are to continue their sponsorship for the long term. Second, if you work for a company or organization that provides products or services of interest to the biology community, please pass this message on to your marketing or marketing communications department or other appropriate group. Please ask them to help support BIOSCI by sponsoring our Web site and explain the uses and benefits of the system to the biology community. If they are interested, they can then contact us for further information at our tech support address, biosci-help@net.bio.net. Our hope is to quickly raise several large corporate/institutional sponsors on our heavily-used WWW locations (some stats appended below), and then end this sponsorship campaign so that our resources can continue to be used for service provision, not fundraising. Many of our specialty newsgroup WWW archives are still used by small communities of scientists (and they haven't been heavily promoted yet). While these may be valuable niche markets to some advertisers, it will generate more labor and overhead having to find these sponsors, fairly price the locations, and deal with lots of smaller sponsorships than fewer mid-to large sponsors. We are striving to keep our operation as lean and efficient as possible since we are not trying to make careers out of running BIOSCI. We are trying if at all possible to avoid the administrative overhead entailed with processing lots of small payments to reach our fundraising goals. I'd like to thank all of you for your help in advance. In helping us, you are also helping yourselves, not only in keeping this resource available for all of the both large and small research communities that we serve, but also by alleviating the need for us to go back and compete with researchers for tight grant dollars! We promised NSF when we were awarded the BIOSCI grant that we would carry out this mission to make the service self-supporting. With your help, we will succeed in continuing BIOSCI's work into its second decade. Thank you very much! Sincerely, Dave Kristofferson BIOSCI/bionet Manager biosci-help@net.bio.net A list of our prime WWW sponsorship locations follow. Please contact us for further details. ---------------------------------------------------------------------- The overall BIOSCI WWW pages are currently visited by users from close to 5500 unique computer hosts per week. Web servers only log the Internet computer/host name and frequently more than one individual can connect to us from a particular host. Main home page, http://www.bio.net, visited recently by about 2100 unique hosts per week Main Newsgroups archives page, http://www.bio.net/archives.html, visited recently by about 1200 Unique hosts per week BIO-JOURNALS archive page, http://www.bio.net/BIO-JOURNALS.html, visited recently by about 1000 unique hosts per week. EMPLOYMENT archive pages: http://www.bio.net:80/hypermail/EMPLOYMENT/ and monthly header pages, visited recently by about 800 unique hosts per week. Address database search page, http://www.bio.net/addrsearch.html, visited recently by about 450 unique hosts per week. Methods newsgroup archive pages, http://www.bio.net:80/hypermail/METHDS- REAGNTS/ and monthly header pages, visited recently by about 350 unique hosts per week. Ads can also be displayed on various combinations of other BIOSCI/bionet newsgroups. Please contact us at biosci-help@net.bio.net for details. ---------------------------------------------------------------------- From owner-gene-linkage@net.bio.net Sun Jun 16 23:00:00 1996 Path: biosci!PO-BOX.MCGILL.CA!imurra From: imurra@PO-BOX.MCGILL.CA Newsgroups: bionet.molbio.gene-linkage Subject: Genetics of obesity Date: 17 Jun 1996 15:48:28 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 10 Sender: daemon@net.bio.net Distribution: world Message-ID: <199606172246.SAA11273@sirocco.CC.McGill.CA> NNTP-Posting-Host: net.bio.net Hello, I am studying the genetics of obesity. Does anyone know of a method to selectively enrich cDNA for signal sequences for extracellular/membrane secretion? Thanks for your help, I can be e-mailed at: imurra@po-box.mcgill.ca From owner-gene-linkage@net.bio.net Sun Jun 16 23:00:00 1996 Path: biosci!bcm.tmc.edu!pendragon!news.msfc.nasa.gov!newsfeed.internetmci.com!uwm.edu!caen!reeve.research.aa.wl.com!dom006.dom.aa.wl.com!user From: pumiglk@aa.wl.com (Kevin Pumiglia) Newsgroups: bionet.molbio.gene-linkage Subject: cDNA to Chromosomal Location Date: 17 Jun 1996 19:57:19 GMT Organization: U of Michigan/Parke-Davis Lines: 12 Message-ID: NNTP-Posting-Host: dom006.dom.aa.wl.com Hello Fellow Netters: I am looking for information on the fastest way to get from a cDNA to the chromosomal location. Is FISH the best way? Radiation hybrid mapping? What are the requirements for these methods? ANY information that would point me in the right direction is appreciated! Please respond to my e-mail address: printej@aa.wl.com Thanks! John From owner-gene-linkage@net.bio.net Sun Jun 16 23:00:00 1996 Path: biosci!GEMINI.OSCS.MONTANA.EDU!uchih From: uchih@GEMINI.OSCS.MONTANA.EDU (Ina Hoeschele) Newsgroups: bionet.molbio.gene-linkage Subject: (none) Date: 17 Jun 1996 16:14:30 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 67 Sender: daemon@net.bio.net Distribution: world Message-ID: <9606172310.AA02135@gemini.oscs.montana.edu> NNTP-Posting-Host: net.bio.net ***** Postdoctoral Position available ********************************* ***** Desired Start Date: September 1, 1996 (August 1 - October 1) **** ******************* Area of Research: ******************************* ***** Statistical Gene Mapping and Markov Chain Monte Carlo *********** ******************* Location: *************************************** ******** Department of Dairy Science ********************************** ** Virginia Polytechnic Institute and State University **************** I am offering a postdoctoral position with funding available for up to two years. Two previous postdoctoral associates have worked on this project with great success and productivity (3-5 papers each). The research is funded by the National Science Foundation and the US Department of Agriculture. The successful candidate will contribute in some of the following areas: (i) Generalization of software developed for Bayesian and Residual Maximum Likelihood statistical gene mapping to pedigree structures other than granddaughter designs. (ii) Continuation of work on fitting several linked QTLs per chromosome. (iii) Further optimization of linkage analysis software, including parallelization. (iv) Analysis of large genetic marker data sets with above methods and with simpler methods, including nonparametric approaches. (v) Further developments of efficient Markov chain Monte Carlo (including Gibbs sampling) algorithms for gene mapping, models including mapped genes and (non)linear models. (vi) Further developments of tests for the nature of QTLs (single biallelic or multiallelic, polygenic) (vii) Linkage analysis with multiple traits and categorical traits. The successful candidate will be given the opportunity to teach and collaborate on other projects, if desired. He/she will work in a team of two PhD students and two postdoctorals, and probably one or two visiting scientists. The candidate must be (i) well trained in Statistics and Genetics and hold a PhD degree in either field, and (ii) familiar with Fortran programming and Unix environments. The ideal candidate is also (iii) somewhat familiar with major gene and linkage analyses (iv) eager to succeed and exercise initiative (v) reliable and a good team member Please send applications including Curriculum Vitae, list of publications, and three references to email: inah@vt.edu fax: (USA) 406 994 1895 c/o Ina Hoeschele (before Aug.10) (USA) 540 231 5014 c/o Ina Hoeschele (after Aug.10) Feel free to contact me by email first if you like to obtain more information about this position. Virginia Polytechnic Institute and State University provides a productive research environment with 11 animal geneticists (a mix of animal breeders, statistical geneticists and molecular geneticists) and a large Statistics department (offering also classes in statistical genetics and biostatistics), providing the possibility for interaction and auditing of classes. There is also interaction with a Human Genetics group in Richmond, VA, including Drs. Charles MacLean and Mike Neale. Finally, the computing facilities are excellent (departmental high-end, multi-processor workstation, computing center workstations, symmetric multi-processor and SP2 systems, and supercomputing access at the Cornell Theory Center). Ina Hoeschele Associate Professor of Quantitative Genetics From owner-gene-linkage@net.bio.net Sun Jun 16 23:00:00 1996 Path: biosci!HOMER.LOUISVILLE.EDU!dlrobi02 From: dlrobi02@HOMER.LOUISVILLE.EDU ("David L. Robinson") Newsgroups: bionet.molbio.gene-linkage Subject: teaching electrophoresis to freshmen Date: 17 Jun 1996 16:24:32 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 48 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net I am currently developing the laboratory component of a freshman, introductory biology class (for majors) that I teach in the fall. I want to demonstrate electrophoresis in lab, and am trying to figure out the most effective way to do it. Does anyone have any good ideas? I know I could do a demonstration SDS-protein gel showing the protein profiles of different species/tissues, or I could do lambda restriction digests and run a DNA gel, but: 1) I only have 3 hours per lab period for each group of students, 2) I teach multiple sections so this would be really a strain in terms of time and expense, 3) I'd rather not have a bunch of 18-year-olds playing around with things like acrylamide, ethidium bromide, etc. 4) I could just as easily show publication-quality photos of protein or DNA gels that are already in the literature or textbooks....what I really want them to appreciate is the *concept* of electrophoresis.....that you can separate molecules based on their size, charge and shape using an electric field. Once they understand that then they can start to deal with actual protein/DNA/RNA gels. Last year, after I had them do paper chromatography exercises in separating chlorophyll and then amino acids I was able to just say that electrophoresis was "sort of like that except.....la la la". But I am not sure paper chromatography is conceptually a real good analogy for electrophoresis! Plus, I would like them to at least *see* some of the basic equipment that is used in cellular/molecular biology even if they don't get to actually use it themselves. Now my idea is to pour an agarose gel for them, and load a well with a single, dark solution that would be a mixture of different dyes and then apply current. The dyes would move at different rates and separate out. In my imagination they would see lots of bands of red, blue, green, etc that had been separated by electric force. That would be the end of it...without any other steps I would have demonstrated the basic process of electrophoresis. Comments????? Does anyone have any good ideas for what dyes would be good for this? I can use bromophenol blue and xylene cyanole as they are different in color and mobility in an agarose system.....what other dyes of different color and mobility can I add to this mixture? Thanks for any advice. Dave Lowell Robinson dlrobi02@homer.louisville.edu Biology Department Bellarmine College Louisville, KY From owner-gene-linkage@net.bio.net Mon Jun 17 23:00:00 1996 Path: biosci!GEMINI.OSCS.MONTANA.EDU!uchih From: uchih@GEMINI.OSCS.MONTANA.EDU (Ina Hoeschele) Newsgroups: bionet.molbio.gene-linkage Subject: (none) Date: 18 Jun 1996 11:17:12 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 67 Sender: daemon@net.bio.net Distribution: world Message-ID: <9606181810.AA29373@gemini.oscs.montana.edu> NNTP-Posting-Host: net.bio.net ***** Postdoctoral Position available ********************************* ***** Desired Start Date: September 1, 1996 (August 1 - October 1) **** ******************* Area of Research: ******************************* ***** Statistical Gene Mapping and Markov Chain Monte Carlo *********** ******************* Location: *************************************** ******** Department of Dairy Science ********************************** ** Virginia Polytechnic Institute and State University **************** I am offering a postdoctoral position with funding available for up to two years. Two previous postdoctoral associates have worked on this project with great success and productivity (3-5 papers each). The research is funded by the National Science Foundation and the US Department of Agriculture. The successful candidate will contribute in some of the following areas: (i) Generalization of software developed for Bayesian and Residual Maximum Likelihood statistical gene mapping to pedigree structures other than granddaughter designs. (ii) Continuation of work on fitting several linked QTLs per chromosome. (iii) Further optimization of linkage analysis software, including parallelization. (iv) Analysis of large genetic marker data sets with above methods and with simpler methods, including nonparametric approaches. (v) Further developments of efficient Markov chain Monte Carlo (including Gibbs sampling) algorithms for gene mapping, models including mapped genes and (non)linear models. (vi) Further developments of tests for the nature of QTLs (single biallelic or multiallelic, polygenic) (vii) Linkage analysis with multiple traits and categorical traits. The successful candidate will be given the opportunity to teach and collaborate on other projects, if desired. He/she will work in a team of two PhD students and two postdoctorals, and probably one or two visiting scientists. The candidate must be (i) well trained in Statistics and Genetics and hold a PhD degree in either field, and (ii) familiar with Fortran programming and Unix environments. The ideal candidate is also (iii) somewhat familiar with major gene and linkage analyses (iv) eager to succeed and exercise initiative (v) reliable and a good team member Please send applications including Curriculum Vitae, list of publications, and three references to email: inah@vt.edu fax: (USA) 406 994 1895 c/o Ina Hoeschele (before Aug.10) (USA) 540 231 5014 c/o Ina Hoeschele (after Aug.10) Feel free to contact me by email first if you like to obtain more information about this position. Virginia Polytechnic Institute and State University provides a productive research environment with 11 animal geneticists (a mix of animal breeders, statistical geneticists and molecular geneticists) and a large Statistics department (offering also classes in statistical genetics and biostatistics), providing the possibility for interaction and auditing of classes. There is also interaction with a Human Genetics group in Richmond, VA, including Drs. Charles MacLean and Mike Neale. Finally, the computing facilities are excellent (departmental high-end, multi-processor workstation, computing center workstations, symmetric multi-processor and SP2 systems, and supercomputing access at the Cornell Theory Center). Ina Hoeschele Associate Professor of Quantitative Genetics From owner-gene-linkage@net.bio.net Mon Jun 17 23:00:00 1996 Path: biosci!bcm.tmc.edu!pendragon!news.msfc.nasa.gov!elroy.jpl.nasa.gov!swrinde!newsfeed.internetmci.com!torn!webster.srv.gc.ca!news.agr.ca!news@news.agr.ca From: "Nicholas A. Tinker" Newsgroups: bionet.molbio.gene-linkage Subject: Mapmaker Postscrip files Date: Tue, 18 Jun 1996 14:45:52 -0400 Organization: E.C.O.R.C., Agric. and Agrifood Canada Lines: 15 Message-ID: <31C6F960.2E1C@em.agr.ca> References: NNTP-Posting-Host: agc6.agr.ca Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 2.01 (Win95; I) Hello, Are there any Mapmaker users out there who know how to import postscript files produced by Mapmaker into a drawing package? I would like to be able to use Freelance, but freelance will only read "encapsulated postcript files". What's the dif? Nick Tinker (tinkerna@em.agr.ca) --------------------------------------- Any opinions expressed here are my own; they may not represent the opinions of Agriculture and Agri-food Canada From owner-gene-linkage@net.bio.net Mon Jun 17 23:00:00 1996 Path: biosci!EM.AGR.CA!GHumphreys From: GHumphreys@EM.AGR.CA (Gavin Humphreys) Newsgroups: bionet.molbio.gene-linkage Subject: An original mapping population Date: 18 Jun 1996 14:30:40 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 15 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Hello: I would like to do QTL mapping for protein content in wheat. However, the mapping population that is available,is a double haploid (DH) population of a donor x F1 (ie C X(AxB)). Hence, 3 possible alleles will be present in the dh population. As far as I am aware Mapmaker will only allow me to enter two alleles (ie. A or B). I was wondering if anyone knows of programs that could be used to handle this kind of RFLP data. I presume that crops such as alfalfa must have to deal with this sort of data. Thanks, Gavin PS Please send replies directly to me since I do not subscribe to this group. From owner-gene-linkage@net.bio.net Tue Jun 18 23:00:00 1996 Path: biosci!rutgers!uwm.edu!vixen.cso.uiuc.edu!newsfeed.internetmci.com!torn!webster.srv.gc.ca!news.agr.ca!news@news.agr.ca From: "Nicholas A. Tinker" Newsgroups: bionet.molbio.gene-linkage Subject: Drawing linkage maps Date: Wed, 19 Jun 1996 16:24:15 -0400 Organization: E.C.O.R.C., Agric. and Agrifood Canada Lines: 11 Message-ID: <31C861EF.3B8A@em.agr.ca> References: <31C6F960.2E1C@em.agr.ca> NNTP-Posting-Host: agc6.agr.ca Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 2.01 (Win95; I) Hello, I had many useful replies to my question about exporting Mapmaker postscript files to some other format. The most useful sugestions were that "Ghostscript" would export EPS format, and that CorelDraw would import both PS and EPS. Unfortunately, after a day of trying, neither solution works. Maybe it's time to look for a new way of drawing chromosome linkage maps........ any sugestions? From owner-gene-linkage@net.bio.net Wed Jun 19 23:00:00 1996 Path: biosci!CS.Arizona.EDU!news.Arizona.EDU!hamblin.math.byu.edu!acs2.byu.edu!news.cuny.edu!news.sprintlink.net!news-stk-200.sprintlink.net!news.sprintlink.net!news-stk-11.sprintlink.net!news.texas.net!nntp.primenet.com!news.cais.net!world1.bawave.com!newsfeed.internetmci.com!uwm.edu!cs.utexas.edu!geraldo.cc.utexas.edu!netnews.uthscsa.edu!usenet From: humberto@momo.uthscsa.edu (Humberto Ortiz Zuazaga) Newsgroups: bionet.molbio.gene-linkage Subject: Re: Drawing linkage maps Date: 20 Jun 1996 10:07:47 -0500 Organization: University of Texas Health Science Center at San Antonio Lines: 36 Sender: humberto@momo.uthscsa.edu Message-ID: References: <31C6F960.2E1C@em.agr.ca> <31C861EF.3B8A@em.agr.ca> NNTP-Posting-Host: momo.uthscsa.edu In-reply-to: "Nicholas A. Tinker"'s message of Wed, 19 Jun 1996 16:24:15 -0400 X-Newsreader: Gnus v5.1 >>>>> "NAT" == "Nicholas A Tinker" writes: NAT> Hello, I had many useful replies to my question about NAT> exporting Mapmaker postscript files to some other format. NAT> Maybe it's time to look for a new way of drawing chromosome NAT> linkage maps........ NAT> any sugestions? I've written a small bioTk program for drawing linkage and radiation hybrid maps. It can export a map as encapsulated postscript (it just uses tcl to dump the canvas). We've imported the maps into Word for Windows documents with no problems. You can get a beta version of my program from: We've also submitted an abstract on this program to ASHG'96. I've gotten this program to run on PC's with tcl/tk 4.1, but it requires a little tinkering with tkmap and some modifications to bioTk (bioTk tries to execute "ls" to get a file listing for it's filebox). I don't know if I can distribute a single package containing all my modifications, but I'll try to put diffs for Windows users on my page. bioTk made writing this program a cinch, as a matter of fact, I had the first prototype for this program running in a couple of minutes, with my boss watching over my shoulder. -- Humberto Ortiz-Zuazaga Cellular & Structural Biology humberto@momo.uthscsa.edu http://momo.uthscsa.edu/~humberto/ From owner-gene-linkage@net.bio.net Thu Jun 20 23:00:00 1996 Newsgroups: bionet.molbio.gene-linkage Path: biosci!daresbury!lyra.csx.cam.ac.uk!hgmp.mrc.ac.uk!ebi.ac.uk!uranus.ebi.ac.uk!tome From: tome@uranus.ebi.ac.uk (Patricia Rodriguez-Tome) Subject: Re: Drawing linkage maps Sender: news@ebi.ac.uk (Petteri Jokinen) Message-ID: Date: Thu, 20 Jun 1996 17:12:57 GMT Lines: 48 Reply-To: tome@ebi.ac.uk References: <31C6F960.2E1C@em.agr.ca> <31C861EF.3B8A@em.agr.ca> Organization: European Bioinformatics Institute (EMBL) - UK X-Newsreader: mxrn 6.18-31 In article <31C861EF.3B8A@em.agr.ca>, "Nicholas A. Tinker" writes: >Hello, >I had many useful replies to my question about exporting Mapmaker >postscript files to some other format. The most useful sugestions were >>that "Ghostscript" would export EPS format, and that CorelDraw would >import both PS and EPS. Unfortunately, after a day of trying, neither >>solution works. > >Maybe it's time to look for a new way of drawing chromosome linkage >maps........ > >any sugestions? > Hello, CorelDraw and others will "import" Ps or EPS files (as will xfig on unix) but you wont be able to modify (only resize) them. Sometimes you won't even see them on the screen while they will appear in the document. That is because their own format (ie the default when they read/write) is not PS. We had the same problem when I was working at genethon. We ended up writing a program where the output was Poscript but following the format for AdobeIllustrator (because that format is at Adobe site ) so we were then able to import them in Illustrator (with some problem - where was the bug;-) But it worked and the files could be modified. that is the program that was used for the Genethon genetic map (see Nature Genetics) So I suppose the solution is writing the output in a Postscript format a program can read and modify. Maybe there are filters out there? I don't know any but the ftp.adobe.com site seems a good place to look at. go into the pub directory Cheers PatRT -- ======================================================================= Dr. Patricia Rodriguez-Tome | URL: http://www.ebi.ac.uk The EMBL Outstation, Hinxton - The European Bioinformatics Institute Hinxton Hall, Hinxton | Tel: +44 (0)1223 494 409 Cambridge CB10 1RQ, UK | Fax: +44 (0)1223 494 468 ======================================================================== From owner-gene-linkage@net.bio.net Tue Jun 25 23:00:00 1996 Newsgroups: bionet.molbio.gene-linkage Path: biosci!CS.Arizona.EDU!news.Arizona.EDU!hamblin.math.byu.edu!sol.ctr.columbia.edu!spool.mu.edu!uwm.edu!cs.utexas.edu!howland.reston.ans.net!math.ohio-state.edu!jussieu.fr!univ-lyon1.fr!in2p3.fr!swidir.switch.ch!swsbe6.switch.ch!news.belnet.be!news.vub.ac.be!hnets.uia.ac.be!news From: Peter Van Osta Subject: Automatic genotyping software X-Nntp-Posting-Host: neurogen20.uia.ac.be Content-Type: text/plain; charset=us-ascii Message-ID: <31D12232.6208AC23@uia.ua.ac.be> Sender: news@uia.ua.ac.be (News database) Content-Transfer-Encoding: 7bit Organization: Laboratory of Neurogenetics University of Anwerp (UIA) Mime-Version: 1.0 Date: Wed, 26 Jun 1996 11:42:42 GMT X-Mailer: Mozilla 2.0 (X11; I; Linux 2.0.0 i586) Lines: 42 Hello, We are using ABI-377 (and ABI-373) sequencers with ABi-software to do genome searches. Although there is a program called genotyper available from ABI (running on Mac) I am looking for a program that would accept ABI-data from the Mac and that could do the genotyping on Unix (Linux 2.0.0 / Slakware 3.0). Our Macs are linked to the Linuxbox (ehernet) and I am using Netatalk to tranfer data from/to the Linuxbox, so exchanging the data is not a problem. Linux on PC provides with a powerful but cheap platform to do linkage-analysis, but I want to improve the dataflow to the linkage-programs by automating the data-transfer to the linkage-software. Peter Van Osta, MD please email. -- Neurogenetics and Protein Chemistry Department of Biochemistry University of Antwerp (UIA), building T Universiteitsplein 1 B-2610 Antwerpen Belgium tel.: +32 3 820 23 23 (am, GMT +1) +32 3 820 23 22 (pm) fax.: +32 3 820 25 41 email: pvosta@uia.ua.ac.be WWW: http://alt-www.uia.ac.be/u/pvosta/welcome.html From owner-gene-linkage@net.bio.net Thu Jun 27 23:00:00 1996 Path: biosci!bcm.tmc.edu!cs.utexas.edu!usc!chi-news.cic.net!news.compuserve.com!news.production.compuserve.com!news From: Pierre Dion <102605.2065@CompuServe.COM> Newsgroups: aus.mbio,bionet.molbio.bio-matrix,bionet.molbio.genbank,bionet.molbio.gene-linkage,sci.research.careers Subject: Molecular/Cellular RESEARCH-TORONTO Date: 28 Jun 1996 15:40:42 GMT Organization: Dion Management Consulting Group Lines: 24 Message-ID: <4r0udq$4dt$1@mhade.production.compuserve.com> Xref: biosci bionet.molbio.bio-matrix:740 bionet.molbio.genbank:2319 bionet.molbio.gene-linkage:1100 sci.research.careers:11051 We have recently been mandated by a prominent Canadian biotechnological company to recruit a person to head their molecular and cellular research. Our client's mission is focused upon discovering and developing innovative therapeutics using modern molecular and chemical technologies. Significant disease targets are identified through advanced biological techniques. Strategic alliances are an integral part of corporate strategy for moving in-house technologies to commercialization. The incumbent will report to the senior Vice-President, Research and Clinical Development, and will directly supervise five to six people and indirectly between twenty-five to thirty-five people. We are looking for people with a Ph.D. in Molecular Biology/Biochemistry and at least 8 years research experience in an industrial environment following postdoctoral training in relevant experimental areas in a multidisciplinary environment. This position is located in Toronto with an attractive compensation package. If you are interested in submitting your resume or obtaining more information about this position, please contact Marlene Harris at 800 261-3204. -- Dion From owner-gene-linkage@net.bio.net Sat Jun 29 23:00:00 1996 Path: biosci!GEMINI.OSCS.MONTANA.EDU!uchih From: uchih@GEMINI.OSCS.MONTANA.EDU (Ina Hoeschele) Newsgroups: bionet.molbio.gene-linkage Subject: (none) Date: 30 Jun 1996 13:14:19 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 73 Sender: daemon@net.bio.net Distribution: world Message-ID: <9606291426.AA03230@gemini.oscs.montana.edu> NNTP-Posting-Host: net.bio.net !!! One more chance !!! !!! Interesting project and funding for 1 or 2 years available !!! !!! Location: Virginia Polytechnic Institute and State University !!! !!! Blacksburg, Virginia !!! ***** Postdoctoral Position available ********************************* ***** Desired Start Date: September 1, 1996 (September - December) **** ******************* Area of Research: ******************************* ***** Statistical Gene Mapping and Markov Chain Monte Carlo *********** ******************* Location: *************************************** ******** Department of Dairy Science ********************************** ** Virginia Polytechnic Institute and State University **************** I am offering a postdoctoral position with funding available for up to two years. Two previous postdoctoral associates have worked on this project with great success and productivity (3-5 papers each). The research is funded by the National Science Foundation and the US Department of Agriculture. The successful candidate will contribute in some of the following areas: (i) Generalization of software developed for Bayesian and Residual Maximum Likelihood statistical gene mapping to pedigree structures other than granddaughter designs. (ii) Continuation of work on fitting several linked QTLs per chromosome. (iii) Further optimization of linkage analysis software, including parallelization. (iv) Analysis of large genetic marker data sets with above methods and with simpler methods, including nonparametric approaches. (v) Further developments of efficient Markov chain Monte Carlo (including Gibbs sampling) algorithms for gene mapping, models including mapped genes and (non)linear models. (vi) Further developments of tests for the nature of QTLs (single biallelic or multiallelic, polygenic) (vii) Linkage analysis with multiple traits and categorical traits. The successful candidate will be given the opportunity to teach and collaborate on other projects, if desired. He/she will work in a team of two PhD students and two postdoctorals, and probably one or two visiting scientists. The candidate must be (i) well trained in Statistics and Genetics and hold a PhD degree in either field, and (ii) familiar with Fortran programming and Unix environments. The ideal candidate is also (iii) somewhat familiar with major gene and linkage analyses (iv) eager to succeed and exercise initiative (v) reliable and a good team member Please send applications including Curriculum Vitae, list of publications, and three references to email: inah@vt.edu fax: (USA) 406 994 1895 c/o Ina Hoeschele (before Aug.10) (USA) 540 231 5014 c/o Ina Hoeschele (after Aug.10) Feel free to contact me by email first if you like to obtain more information about this position. Virginia Polytechnic Institute and State University provides a productive research environment with 11 animal geneticists (a mix of animal breeders, statistical geneticists and molecular geneticists) and a large Statistics department (offering also classes in statistical genetics and biostatistics), providing the possibility for interaction and auditing of classes. There is also interaction with a Human Genetics group in Richmond, VA, including Drs. Charles MacLean and Mike Neale. Finally, the computing facilities are excellent (departmental high-end, multi-processor workstation, computing center workstations, symmetric multi-processor and SP2 systems, and supercomputing access at the Cornell Theory Center). Ina Hoeschele Associate Professor of Quantitative Genetics From owner-gene-linkage@net.bio.net Sun Jun 30 23:00:00 1996 Path: biosci!bcm.tmc.edu!pendragon!news.msfc.nasa.gov!newsfeed.internetmci.com!howland.reston.ans.net!vixen.cso.uiuc.edu!cdc2.cdc.net!newsfeed.concentric.net!news.sojourn.com!news.eecs.umich.edu!newshub.tc.umn.edu!newsstand.tc.umn.edu!lenti From: dean@lenti.med.umn.edu (Dean Flanders) Newsgroups: bionet.molbio.gene-linkage Subject: BIONET.MOLBIO.GENE-LINKAGE.FAQ Date: 1 Jul 1996 05:00:24 GMT Organization: University of MN, Medical School Lines: 987 Message-ID: <4r7m18$nmo@epx.cis.umn.edu> NNTP-Posting-Host: lenti.med.umn.edu Originator: dean@lenti.med.umn.edu BIONET.MOLBIO.GENE-LINKAGE FREQUENTLY ASKED QUESTIONS (FAQ) AS OF 1996/04/29 1.0) FAQ ADMINISTRATIVE INFORMATION [1995/05/18] 1.1) Where can I obtain and/or access the bionet.molbio.gene-linkage FAQ? [1995/03/01] 1.2) Who created the bionet.molbio.gene-linkage FAQ? [1995/03/01] 1.3) How can I help improve this FAQ? [1995/03/01] 1.4) Contributors to this FAQ. [1995/09/09] 1.5) When was the FAQ last updated? [1996/04/28] 2.0) INFORMATION RESOURCES 2.1) What anonymous FTP sites have programs/utilities useful for linkage analysis? [1995/03/01] 2.2) What books are helpful when learning about linkage analysis? [1995/03/01] 2.3) What WWW sites have useful linkage information? [1996/01/02] 2.4) What gopher sites have useful linkage information? [1995/03/01] 2.5) What "linkage centers" make information and assistance available to researchers? [1995/12/11] 2.6) What journals are useful for linkage analysis? [1995/06/02] 2.7) What courses are offered in linkage analysis? [1995/09/09] 3.0) GENE-LINKAGE SOFTWARE OVERVIEW 3.1) What database management programs do people use for linkage data? [1995/05/31] 3.2) What programs are available for pedigree drawing? [1995/04/01] 3.3) What linkage analysis helper programs are available? [1996/04/29] 3.4) Why are some programs used primarily for chromosome mapping, while others are used for disease mapping? [1995/03/01] 3.5) What programs are used for physical mapping? [1995/11/30] 3.6) What programs are used for disease gene mapping? [1995/09/07] 3.7) What programs are available for running genetic simulations? [1995/11/30] 3.8) What programs are available to help detect errors in linkage data? [1995/11/30] 3.9) What programs help me recode genetic markers? [1995/03/01] 4.0) LINKAGE PACKAGE SPECIFIC INFORMATION 4.1) How do I get my CEPH data into CRI-MAP format? [1995/03/01] 4.2) How do you calculate MAXHAP? [1995/09/09] 4.3) When should you use binary coding instead of numeric allele coding? [1995/03/01] 4.4) What do you do when allele frequencies do not add up to 1; for example, when alleles are not present in a pedigree under study? [1995/03/01] 4.5) I use LINKAGE and/or FASTLINK. Which references should I include in my papers? [1995/03/01] 4.6) What is recoding of alleles all about anyway? [1995/03/01] 4.7) What do you do when you get thetas greater than 0.5 when using linkage? [1996/22/01] 5.0) COMPUTER ADMINISTRATION AND OPTIMIZATION 5.1) How w can I increase the speed of the LINKAGE/FASTLINK package on my workstation? [1995/05/18] 6.0) MOLECULAR BIOLOGY ISSUES IN LINKAGE ANALYSIS 6.1) What screening sets are available for linkage analysis? [1995/09/14] 1.0) FAQ ADMINISTRATIVE INFORMATION 1.1) Where can I obtain the bionet.gene-linkage FAQ? [1995/03/01] It is available by anonymous FTP from lenti.med.umn.edu in /pub/linkage. The best way to view the FAQ is via the WWW, from http://lenti.med.umn.edu/linkage/linkage.html. The FAQ is also available via gopher at lenti.med.umn.edu in /Biologically Related Information/Linkage Analysis. The FAQ will also be posted in the USENET groups bionet.molbio.gene-linkage and news.answers the 1st and 15th of each month. 1.2) Who created the bionet.molbio.gene-linkage FAQ? [1995/03/01] Darrell Root (rootd@ohsu.edu) originally started the bionet.molbio.gene-linkage FAQ in May of 1994 in an attempt to share information and experiences that may be of use to other people involved in linkage analysis. I am Dean Flanders (dean@lenti.med.umn.edu), the current maintainer of the FAQ, and began my tenure in December of 1994. The FAQ will never serve as a short course in linkage analysis, but instead it will ideally be a place to help beginners get started in the area and to help experts not make the same mistakes as others. All of the information in this FAQ by no means comes completely from Darrell or me, but from a large number of people that work in the area of linkage analysis. Their names are listed at the end of this section of the FAQ. 1.3) How can I help improve this FAQ? [1995/03/01] Feel free to send any information that you think would be beneficial for other people who are just beginning in linkage or have been doing linkage for years to linkage@lenti.med.umn.edu. Also, if there is information you would like to see or errors in this FAQ please let us know by sending email to linkage@lenti.med.umn.edu. If you would like to see something changed or added to the FAQ please to send it in a format that can be quickly incorporated into the FAQ, such as correcting the errors in the section of the FAQ and emailing it back to the FAQ maintainer. 1.4) Contributors to this FAQ. [1995/09/09] David Adler, John Attwood, Michael Boehnke, Marcia Brott, Don Bowden, Michael Braverman, Lucien Bachner, Young B Choi, Kevin Crawford, Dave Curtis, Peter Doris, Bennett Dyke, David Featherstone, Dean Flanders, Jonathan Haines, Rob Harper, Pierre Janssens, David Kikuchi, Wentian Li, Tim Little, Tara Matise, Eli Meir, Mike Miller, Jurg Ott, Darrell Root, Alex Schaffer, Robert Stodola, Frank Visser, Dan Weeks, Ellen Wijsman, Scott Wildenberg, Matthias Wjst, and Kim Worley. 1.5) When was the FAQ last updated?[1996/04/29] The last update of the FAQ was on 1996/04/29. All sections should indicate what month and year they were last updated. In addition one can go to the list of updates that are maintained at http://lenti.med.umn.edu/linkage/gefaqup.html. This is a list in chronological order of updates with direct links to the updates in the FAQ. 2.0) INFORMATION RESOURCES 2.1) What anonymous-FTP sites have programs/utilities useful for linkage analysis? [1995/03/01] At present there is no one site that serves as a repository for all linkage software. So the best way of finding FTP site information is to read the software package information below, which should provide all of the necessary FTP information. 2.2) What books are helpful when learning about linkage analysis? [1995/03/01] Bishop, M. J. "Guide to Human Genome Computing." Academic Press, 1994. Davies, K. E. "Human Genetic Diseases - A Practical Approach." IRL Press, Oxford England and Washington, D.C., 1986. Dracopoli, N. C., Haines, J. L., Korf, B. R., Moir, D.T., Morton, C. C., Seidman, C. E., Seidman, J. G., Smith, D. R. "Current Protocols in Human Genetics." John Wiley and Sons, Inc., USA, 1994. Khoury, M. J., Beaty, T. H., and Cohen, B. H. "Fundamentals of Genetic Epidemiology." Oxford University Press, 1993. Ott, J. "Analysis of Human Genetic Linkage." Johns Hopkins University Press, 1991. Terwilliger, J. D. and Ott, J. "Handbook of Human Genetic Linkage," Johns Hopkins University Press, 1994. Thompson, E. A. "Pedigree Analysis in Human Genetics." Johns Hopkins University Press, Baltimore and London, 1986. 2.3) What WWW sites have useful linkage information? [1996/01/02] This is in no way an attempt to list the explosion of WWW sites of biological interest on the Internet, but it is a listing of some of the major ones and ones of particular interest in linkage analysis. http://www.yahoo.com/Science/Biology/Genetics/, this is a list of sites related to genetics that is kept very up to date. http://www.gdb.org/Dan/DOE/intro.html, this is a short course of sorts that gives some very basic information on how to go about gene mapping. http://lenti.med.umn.edu/linkage/linkage.html, which is serving as linkage analysis home page, will have links to all of the WWW sites listed as well as gopher servers and a hypertext version of the FAQ. http://www.genethon.fr, the Genethon Center, Genethon's home page. http://www.chlc.org, the Cooperative Human Linkage Center, CHLC's home page. http://gdbwww.gdb.org has a version of GDB available and access to OMIM. http://www.pathology.washington.edu has human and mouse standard idiograms. The idiograms are useful for making illustrations for gene mapping and for constructing abnormal chromosomes. The PostScript idiograms can be manipulated band by band with illustration software such as Adobe Illustrator, Aldus FreeHand, Canvas, and Altsys Virtuoso. http://www.gene.ucl.ac.uk/~john/programs.html contains software by John Attwood. http://www.gene.ucl.ac.uk/packages/dcurtis/ contains software by Dave Curtis. http://linkage.cpmc.columbia.edu has a lot of useful information on linkage analysis; in particular it offers information on software, the course offered by J. Ott, and the Linkage Newsletter. 2.4) What gopher sites have useful linkage information? [1995/03/01] There is one that will be maintained with links to other gophers of interest in linkage analysis, as well as links to other gopher servers of biologically related information. It is at lenti.med.umn.edu, and the path to it is Biologically Related Information/Genetic Linkage Analysis. 2.5) What "linkage centers" make information and assistance available to researchers? [1995/11/11] One such center is the Cooperative Human Linkage Center (CHLC). The goal of this center is to generate a high resolution map of the human genome and rapidly distribute this information to the genome community. They are in the process of identifying more human markers and developing high resolution framework maps. One can obtain information about CHLC from via gopher from gopher.chlc.org , http://www.chlc.org , ftp://ftp.chlc.org , info-server@chlc.org, or help@chclc.org. Among other things, CHLC provides primer selection and linkage analysis via email. Information on those services can be found by sending email to: primer- server@chlc.org and linkage-server@chlc.org. David Featherston (davidf@caos.kun.nl) from the Dutch EMBnet Node is starting a linkage analysis service: software availability, support/advice initially, possibly training, and perhaps consultancy. At present they have MapMaker/EXP 3.0b, MapMaker/QTL 1.1, Lathrop and Lalouel's LINKAGE package, and Schaffer's FASTLINK package. This means that if users have Genomics Package accounts at the CAOS/CAMM Center, they can use these programs on their fast computers to analyze their data sets. Please contact David Featherston if you are interested in more information about such an account. A major European center is the Human Genome Mapping Project Resource Centre in Hinxton, England. It is funded by the Medical Research Council, and has a broad range of software and databases available, mainly focused on the Human Genome Project. In the area of Linkage analysis it has the following programs available: FASTLINK, CRIMAP, MAP MAPMAKER, HOMOZ, PEDPACK, APM, SIMLINK, FASTMAP, COMDS, DOLINK & QDB, HANDLINK, GAS and Jurg Ott's collection of programs. The aim is to have all major (Unix-based) gene linkage packages available for our users. The Center also gives courses on linkage analysis. More information about the Centre can be obtained from it's home- page: http://www.hgmp.mrc.ac.uk/. If you want to register as user, send e-mail to admin@hgmp.mrc.ac.uk for a registration form. For more information about the gene-linkage services you can contact Frank Visser (fvisser@hgmp.mrc.ac.uk). INFOBIOGEN: This is the French GDB node that offers also a linkage server and assistance in the process of linkage analysis. It uses LINKAGE, FASTLINK and other programs running on a Sparc Center 2000E with 1 giga RAM, 4 Gig of swap, and 6 CPU's. For furhter information contact Lucien Bachner at bachner@infobiogen.fr or look at the following web site http://www.infobiogen.fr/. 2.6) What journals are useful for linkage analysis? [1995/06/02] American Journal of Human Genetics, Annals of Human Genetics, Computer Applications in Biosciences (CABIOS), Genomics, Genetic Epidemiology, Human Genome News (available by gopher from gopher.gdb.org), Human Genome Project Journal, Human Heredity, Journal of Computational Biology, Nature Genetics. 2.7) What courses are offered on linkage analysis? [1995/09/09] There are three primary courses offered throughout the yeart on human linkage analysis. One is a four day course offered once per year by Drs. Margaret Pericak-Vance and Jonathan Haines. The next course will be offered in late April, 1996 in Boston. The focus of the course is on the overall design of a human disease gene mapping study, with particular emphasis on the problems of common/complex disorders. The course covers clinical classification, pedigree ascertainment, collection, and follow-up, basic linkage techniques, linkaghe and association analysis for complex disorders, laboratroy technqiues for genotyping, and gene characterization. The courseemphasizes the global decision-making process, rather than details of specific techniques. For more information write to Genetic Methods Course; c/o Dr. Margaret Pericak- Vance; Division of Neurology, Box 2900; Duke University Medical Center; Durham, NC 27710, or you can send e-mail to genclass@genemap.mc.duke.edu. The remaining two courses are both offered by Jurg Ott on the software used for human linkage. One is a beginner's course, and the other an advanced course for those familiar with the linkage analysis software. These courses are offered several times throughout the year and you can get more information by contacting Katherine Montague/Jurg Ott; Columbia University, Unit 58; 722 West 168th Street; New York, NY 10032. In addition you can fax to (212)568- 2750 or call (212)960 2507 or email km165@columbia.edu for more information. A new beginner's level linkage course will be offered in French October 24-25 1995 by INFOBIOGEN, in Villejuif south suburb of Paris. It's free for all academic institutions. For furhter information contact Lucien Bachner at bachner@infobiogen.fr or linkage@infobiogen.fr. 3.0) GENE-LINKAGE SOFTWARE OVERVIEW 3.1) What database management programs do people use for linkage data? [1995/05/31] One must be aware that some pedigree drawing software can also serve as databases for data as well as drawing pedigrees, see the next question in the FAQ for a description of those packages. CEPH DBMS: The CEPH DataBase Management System is specifically designed for chromosome mapping with CEPH style pedigrees. It can output data in ped.out format for the LINKAGE package. This program can now be picked up via anonymous FTP from ftp.cephb.fr in pub/ceph_genotype_db. DOLINK: This DOS custom database program by D. Curtis manages genetic data and sets up input files for linkage analysis. It is available from ftp.gene.ucl.ac.uk. The DOS and Windows versions of DOLINK program help manage genetic data and setup analysis. It is available with the C++ source allowing compilation on Unix host running X and possibly a Macintosh. File Express: This is a DOS shareware database which can be used to hold data for DOLINK (largely superseded by QDB). It is available as fe51-a/b/c.zip via FTP from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. LABMAN and LINKMAN: These are linkage analysis databases for holding linkage data and exporting it in various formats for linkage analysis. They are available via anonymous FTP from lenti.med.umn.edu in /pub/linkage/labman. These databases were developed by P. Adams of Columbia University. LYNKSYS: This custom-made database program was written by J. Attwood and S. Bryant. Although they continue to use it, J. Attwood suggests using DOLINK instead. LINKSYS is not currently available at any FTP sites. Map Manager: It is a program for the Macintosh which helps analyze the results of genetic mapping experiments using backcrosses, intercrosses, or recombinant inbred strains. In addition it also has tools for statistical analysis of experiments. The program was created by K. F. Manly at the Roswell Cancer Institute and is available via FTP from mcbio.med.buffalo.edu in /pub/MapMgr. QDB: This is a database program available as DOS and Windows versions and with C++ source allowing compilation for X and possibly Macintosh. It is available as qdb16a.zip via FTP from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. 3.2) What programs are available for pedigree drawing? [1995/04/01] One of the tricks of managing individuals in a mapping study is trying to get the database you are using to export your family data in a format acceptable for input into pedigree drawing programs. The marriage between these two can be of great assistance. However, some pedigree drawing programs have databases as a part of the package. CYRILLIC: This is a pedigree editor for Windows with facilities for including marker data which you can then have it output the input files for LINKAGE. It is Windows-based, so input of the pedigree is very efficient. You also have a data form associated with each individual where you can store names and other pertinent data. It also has the ability to interface with most standard PC databases. This program is not public domain and is available from Cherwell Scientific Publishing. If you would like more information send email to csp@sable.ox.ac.uk and they would be very happy to send you a demo of the program. Version 2 of Cyrillic should be coming out late summer of 1995. FTREE: This is a DOS pedigree program written by R. Go at the University of Alabama. GENETREE: GeneTree 1.0 is a DOS package which provides a convenient way to draw family tree diagrams suitable for genetics or genealogy. The package consists of the GeneTree program, which draws pedigree diagrams using a command language; and SC, using a menu driven program that facilitates creation of GeneTree commands. GeneTree and SC are made available with program manuals, examples of family tree diagrams, and a GeneTree Quick Reference Guide. GeneTree is written in C. Note that it is a DRAWING program and does not compute genetic parameters. The GeneTree program is available from wijsman@max.u.washington.edu at a price of $125 (because of licensing fees from a private company which wrote one of the drivers used in the program). KINDRED: This new DOS database program, distributed by Epicenter Software, is specifically designed for linkage analysis. A free demo is available by calling (818)-304-9487. In addition to database duties, this program will draw pedigrees, haplotype marker data, and can output data in LINKAGE format. PEDPAK: This package is designed to handle large datasets for animals. The package was written and distributed by Alan Thomas, who is in Bath, England. The software is not public domain and must be purchased. Pedigree/Draw: It is a Macintosh based program, written by B. Dyke, P. Mamelka, and J. MacCluer. It is available from bdyke@darwin.sfbr.org or Pedigree/Draw; Department of Genetics; Southwest Foundation for Biomedical Research; PO. Box 28147; San Antonio, TX 78228-0147. An upgrade from a previous version is $10, the current version is 4.4. Documentation costs $10 printed and the full package including documentation costs $45. There is a script which converts linkage format to Pedigree/Draw available via anonymous FTP at ftp.ee.pdx.edu in /pub/users/cat/rootd/convert.new. PEDRAW: This program is a pedigree drawing program written by D. Curtis for DOS and available via FTP from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. The most current version is called pedraw16.zip. A companion program to PEDRAW is PEDHELP, it is a pop-up help for PEDRAW. PAP: The Pedigree Analysis Package (PAP) is a set of FORTRAN 77 programs for computing likelihoods and simulating phenotypes of genetic models on pedigrees. It is available via gopher from corona.med.utah.edu in Publicly Accessible Software, probes(sts), etc./software/pap. 3.3) What linkage analysis helper programs are available? [1996/04/29] CEPH2CRI: This program converts to output from the CEPH DBMS into the format useable in CRI- MAP. It can be found at ftp.gene.ucl.ac.uk in /pub/packages/linkage_utils. EASISTAT: This is a DOS statistics package, it contains EASIGRAF which draws graphs of lod scores from the output of FASTMAP. The lod scores first need to be run through the TABLE utility, which is included in the DOLINK and FASTMAP packages. It is available as estat21.zip via anonymous FTP from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. FIRSTORD: A demonstration of a method for preliminary ordering of loci based on two-point lod scores. It is available as DOS executable and C source called first11.zip from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. LINKMEND: A program for converting LINKAGE-format files to MENDEL-format files. It is available by anonymous FTP from watson.hgen.pitt.edu as linkmend.tar.Z. MAP: A program to convert LINKMAP output into a table of multipoint lod scores. It is available by anonymous FTP from watson.hgen.pitt.edu as map.tar.Z. PEDPREP: A program for converting a MENDEL-format pedigree file ('pedm.dat') to a Pedigree/Draw file for graphical display on a Macintosh. It is available by anonymous FTP from watson.hgen.pitt.edu as pedprep.tar.Z. RECODE: A program for recoding character or sized-allele data into numbered-allele data. It is available by anonymous FTP from watson.hgen.pitt.edu as recode.tar.Z. 3.4) Why are some programs used primarily for human chromosome mapping, while others are used for human disease mapping? [1995/03/01] Any family can be used for chromosome mapping, so CEPH has picked a particular family "shape" and generated a large database with these families. Programs designed for chromosome mapping can be optimized for using these families, reducing the time needed for calculations. Only families afflicted with a disease can be used for disease gene mapping. As a result, programs designed for disease gene mapping need to be able to deal with arbitrary pedigrees. In addition, these programs need to be able to handle incomplete penetrance. 3.5) What programs are used for physical mapping? [1995/11/30] CLINKAGE: This is the special version of the LINKAGE programs for 3-generation CEPH pedigrees and codominant markers. The PC and VAX versions are available by FTP from linkage.cpmc.columbia.edu. The Unix version is available from corona.med.utah.edu. CHROMLOOK: This is a program for generating haplotypes of marker data in nuclear pedigrees with all individuals genotyped. It identified both the maternal and paternal recombination events, and provides the resulting haplotypes and recombinants in an easy-to-read format. It should be available via FTP server sometime this summer. It was written by Jonathan Haines and he can be contacted at haines@helix.mgh.harvard.edu. CINTMAX: This program is an extensively modified version of CILINK. It uses map functions to model the transmission of gametes from parent to child. Some of these map functions are multilocus feasible, and so can be used with more than 3 loci at a time. It is available by anonymous FTP from watson.hgen.pitt.edu as cintmax.tar.Z. CRI-MAP: This program has been used for chromosome mapping for years. It has options which can generate maps, calculate order probabilities, and printout recombination data. It works on .gen files with data from CEPH style families. It is written in K& R type C code, and the author Phil Green has successfully ran it on Unix, DOS, VMS, and Macintosh systems. It is not available via anonymous FTP. Phil Green distributes CRI-MAP freely ONLY to academics/academic institutions. Contact him at: Phil Green; Molecular Biotechnology Dept., FJ-20; Fluke Hall on Mason Rd.; Univ. of Washington; Seattle, WA 98195; USA; Phone (206) 685-4341; Fax (206) 685-7344; or email phg@u.washington.edu. FASTMAP: This program produces quick approximation to multipoint lod score, available as a DOS executable and C source as fstmap11.zip from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. MULTIMAP: This LISP based expert system uses an customized version of CRI-MAP to create a chromosome map. It is available via anonymous FTP from chimera.gene.cwru.edu. The authors T. Matise, M. Perlin, and A. Chakravarti continue to improve the code, add new functions, and provide excellent support. When used with the CRI-MAP chrompic option (to find double-recombinations to identify possible errors), it is incredibly useful. This is Unix-only (supported for DEC-Ultrix, HP9000, and Suns). The customized CRI-MAP version (called LISPCRI) is distributed at the FTP site, but was not meant to be used independently of MULTIMAP. MAPMAKER: Dr. Eric Lander; Whitehead Institute; 9 Cambridge Center; Cambridge, MA 02142; mapm%mitwibr@mitvma.mit.edu. MAPMAKER is available via FTP at genome.wi.mit.edu in /pub/mapmaker3. RHMAP: It is a set of three FORTRAN 77 programs that provide the means for a complete statistical analysis of RH mapping data. RH2PT is a program for data description and two-point analysis. It provides estimates of locus-specific retention probabilities and pairwise breakage probabilities, two-point lod scores for linkage of the various marker pairs, and linkage groups. RHMAP is now also available at the following URL http://www.sph.umich.edu/group/statgen/software. If you would like email notification of updates please send email to boehnke@umich.edu. 3.6) What programs are used for disease gene mapping? [1995/09/07] APM: The Affected Pedigree Member Method distribution contains the new APM programs, a new file conversion utility, and a histogram/statistics generator. To build the entire distribution, you need C, Pascal, and FORTRAN compilers, and a make utility is also helpful. The programs which are built include: APM, a program to calculate the single locus statistic over one or several marker loci; SIM, a program to simulate pedigrees and, using output files of APM, test for asymptotic normality of the null distribution; APMMULT, a program to generate the multilocus statistic; SIMMULT, a program like SIM but which simulates recombination and uses the output of APMMULT; CHAPM, a program to convert LINKAGE files to APM files, or APM files of one format to APM files of another format; and HIST, a program to compute various statistical figures, plot a histogram, and compute empirical p-values. The APMember package by D. Weeks is available via anonymous FTP from watson.hgen.pitt.edu. Additionally, there are pre-compiled executables of the APM programs for Sun-OS and Sun-Solaris available as newapm.sunos.tar.Z newapm.solaris.tar.Z. CLUMP: A Monte Carlo method for assessing significance of a case-control association study with a multi-allelic marker, available as DOS executable and C source. It is available as clump.zip via anonymous FTP from ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. ESPA: This is a program used for extended sib pair analysis. It comes in a DOS version and can only look at markers containing 5 alleles. It was written by Lodeijk Sandkuijl and can be obtained by writing to him at Voorstraat 27; Delft 2611 JK; THE NETHERLANDS. ERPA: A program for carrying out nonparametric linkage analysis, available as DOS executable and C source. It is called erpa12.zip via anonymous FTP at ftp.gene.ucl.ac.uk in /pub/packages/dcurtis. FASTLINK: This is a much faster implementation of the main programs in LINKAGE (LODSCORE, ILINK, MLINK, LINKMAP) in C. The code is faster due to the use of new and better algorithms for the time intensive parts of the computation. FASTLINK is distributed by A. A. Schaffer from the FTP site softlib.cs.rice.edu (cd pub/fastlink). Version 1 of FASTLINK was instigated by R. W. Cottingham Jr. with implementation done by R. M. Idury and A. A. Schaffer. Version 2 of FASTLINK includes further improvements implemented by A. A. Schaffer, S. K. Gupta, and K. Shriram, with guidance from R. W. Cottingham Jr. Version 2 includes the capability to recover gracefully from a crash of the computer on which FASTLINK is running. FASTLINK was initially intended for UNIX machines, but the distribution now includes instructions for porting to VMS as well as a version for DOS. FASTLINK allows you to compile in "fast" or "slow" mode (the slow version of FASTLINK is still much faster than the old LINKAGE programs). The "fast" version uses lots of memory, but uses the extra memory to contain some of the intermediate results which are repetitively recalculated in the "slow" version (and the old linkage package). Best speed can be obtained by setting up 300 megs of virtual memory on a Unix workstation and using the "fast" version. Schaffer maintains a mailing list of fastlink users (fastlink-list@cs.rice.edu) to answer queries and keep users up to date. Schaffer, Gupta, and other colleagues at Rice University have implemented parallel versions of FASTLINK for either a shared-memory multiprocessor or a network of UNIX workstations. This version is now available as FASTLINK 2.3P at the above mentioned FTP site. Write to schaffer@cs.rice.edu for more information. GAS: It provides facilities for reading, writing, sectioning and performing statistical analyses on phenotypic and genotypic data and one of its features is sib pair analysis. It has been developed within the Department of Medicine at Oxford University and is available via FTP from well.ox.ac.uk in the directory pub/genetics/gas. GREGOR: It is a piece of DOS based software for producing simulated genetic data. It does not perform linkage analysis, but it may be useful for testing methods or assumptions about linkage analysis. GREGOR is operated by a series of hierarchical menus that permit the user to define hypothetical genetic scenarios (gene positions and effects) and produce simulated data-sets for a variety of population structures. GREGOR is available by FTP from the site sifon.cc.mcgill.ca in pub/McGill-Contrib. Questions should be directed to the authors tinker@agradm.lan.mcgill.ca or mather@agradm.lan.mcgill.ca. LINKAGE: This package of programs was developed by M. Lathrop with help from J. M. Lalouel, C. Jlier, and J. Ott. The LINKAGE package consists of several analysis and several utility programs. Versions are available for DOS, OS2, VAX, and Unix platforms. Here are some of the analysis programs: MLINK: 2-point lod-score calculations at fixed recombination distances; LINKMAP: multipoint lod score calculations at fixed distances; ILINK: calculates the recombination distance with the highest lod-score. Unix versions are available via gopher from corona.med.utah.edu in Publicly Accessible Software, probes(sts), etc./software/linkage, DOS and VMS versions are available from linkage.cpmc.columbia.edu, or on floppy disks, when you write to: Katherine Montague/Jurg Ott; Columbia University, Unit 58; 722 West 168th Street; New York, NY 10032. Send pre-formatted DOS disks if you request linkage by mail. You can send email to km165@columbia.edu if you need more information regarding mail requests for the LINKAGE package. LIPED: This DOS program written by J. Ott calculates probabilities for linkage between disease markers and genetic markers. Its input file differentiates between phenotypes and genotypes. As a result, this program is easiest to use when your data is from "old-style" genetic-markers (such as blood phenotype data). This was one of the first programs to do linkage analysis calculations, the LINKAGE package is more commonly used now. MIM: Multipoint IBD Method: mimintro.txt, mimsetup.txt, mim.txt, changes.txt, testa.dat, and testa.out. SAGE: Statistical Analysis Package for Genetic Epidemiology is composed of 18 programs: AGEON: Estimating the Distribution of Age-of-Onset, ASSOC: marker-trait Associations in Pedigree Data, BCROSS: Genetic Hypothesis for Quantitative Data on Inbred strains, their F1 and Backcross(es), CLUSTR: Power Transformation to Obtain Normality and Homoscedasticity from Clustered Data, FCOR: Family Correlations, FSP: Family Structure Program, LODLINK: Lod Score Linkage Analysis, MAPLOC: Mapping a Disease Related Trait Relative to a Set of Linked markers, MAXFUN: Function maximization Subroutine, REGC,REGD,REGTL,REGTN: Segregation Analysis Programs, RELATE: Relationship to Proband, SIBPAL: Sib-Pair Linkage Analysis, and DBSORT, RENUM, SPLIT: Toolkit Programs. Author Dr. R.C. Elston, address Department of Biometry and Genetics; Louisiana State University Medical Center; 1901 Perdido Street; New Orleans, Louisiana 70112, USA. The email contact address is sage@haldne.biogen.lsumc.edu. It is available for the following operating systems: VAX, SunOS 4.1.x, Apple Macintosh II, and DOS. This program is not shareware and must be bought. X-LINKED APM: X-linked version of the APM programs (single-marker), see APM above for more information on APM. It is available by anonymous FTP from watson.hgen.pitt.edu as xlinkapm.tar.Z. Also, xlinkapm.readm is available there, which is a readme about the X-linked version of the APM programs. 3.7) What programs are available for running linkage simulations? [1995/11/30] FASTSLINK: This is program is just like SLINK (see SLINK below), but it utilizes the enhancements incorporated into FASTLINK. It is available via anonymous FTP from watson.hgen.pitt.edu. SIMAPM: Is the SLINK based simulation program for the APM package. This represents a hacked together package which only runs under a Unix system. You will need FORTRAN, Pascal, and C compilers to use this package. It is available via anonymous FTP from watson.hgen.pitt.edu SIMLINK: This FORTRAN program developed by L. Ploughman and M. Boehnke simulates linkage analysis on a family, and gives you an estimate the probability, or power, of detecting linkage in a given family. It allows the researcher to determine whether a family has sufficient informativeness to detect linkage. SIMLINK requires large quantities of memory. It was written for DOS, but has been ported to many platforms. It is available from: Michael Boehnke; Department of Biostatistics; School of Public Health; University of Michigan; Ann Arbor, MI 48109-2029. No postage-money or blank disks are necessary to get SIMLINK sent to you. SIMLINK may be available via anonymous FTP soon. For further information send email to boehnke@umich.edu. SIMLINK is now also available at the following URL http://www.sph.umich.edu/group/statgen/software. If you would like email notification of updates please send email to boehnke@umich.edu. SLINK: It is a Pascal program developed by D. Weeks, M. Lathrop, and J. Ott. It is similar to SIMLINK. It is more general than SIMLINK in that it allows for partial marker typing at the locus to be generated, but it runs slower than SIMLINK. It is available from linkage.cpmc.columbia.edu and watson.hgen.pitt.edu or on floppies (use the same address as for LINKAGE). 3.8) What programs are available to help detect errors in linkage data? [1995/11/30] Typically the linkage packages in and of themselves will detect errors in linkage data that are obvious, such as impossible phenotypes and genotypes, and obvious errors in pedigrees. Typically the programs will just grind to halt and allow you to fix the error, and try again until you finally succeed. However, errors that "make sense" to linkage programs will not be detected. GENO: It is a genotype entry/edit tool that will allow you to easily enter and manipulate genotyping data. You can also check the quality of your data with the built-in Mendelian inheritance checker. The author the of program is Matt Stephenson and can be reaced at stephenm@bioimage.mfldclin.edu. The program is available via FTP from dgabby.mfldclin.edu in /pub/geno. GENOCHECK: It is an error checking program designed to identify individuals and loci that are likely to contain errors. the statistical method was designed to identify typing error, but is general enough to pinpoint any unlikely genotype still consistent with Mendelian inheritance. The author is Dr. Margaret Gelder Ehm the ftp site is at softlib.cs.rice.edu and it is in /pub/GenoCheck. It is written for Unix. 3.9) What programs help me recode genetic markers? [1995/03/01] DOLINK can downcode alleles automatically. However, the main use of DOLINK is to prepare files for LINKAGE from a database. In addition P. Adams package LABMAN and LINKMAN have features for the recoding of alleles. 4.0) LINKAGE PACKAGE SPECIFIC INFORMATION 4.1) How do I get my CEPH data into CRI-MAP format? [1995/03/01] You can output the file in linkage format and use link2gen in CRI-MAP. The disadvantage here is that your marker names are separated from your data and it's easy to make a mistake and get them mixed up. You can output the file in ped.out format and use CEPH2CRI mentioned above in the FAQ to do the conversion as well. 4.2) How do you calculate MAXHAP? [1995/09/09] MAXHAP is the maximum possible number of haplotypes in your analysis. You multiply together the number of alleles at each locus used in a particular run; not all loci in your dataset, just the loci you are using in that particular calculation. Remember that the affection status counts as two alleles, regardless of the number of liability classes. For example, if a dataset has the following information: the liability classes, marker A has 3 alleles, marker B has 4 alleles, and marker C has 5 alleles and your run includes a LINKMAP run between affection status, marker A, and marker B, then your MAXHAP must be at least 2*3*4=24. FASTLINK 2.3P includes an auxiliary program called ofm (optimize for maxhap) which can be used to automatically recompile the desired program with the ideal value of maxhap under the following assumptions: using UNIX or VMS (not DOS), running ILINK or LINKMAP or MLINK (not LODSCORE), the main script is produced by the LINKAGE auxiliary program LCP), and the locus file is produced by the LINKAGE auxiliary program PREPLINK; see README.ofm in the FASTLINK distribution. 4.3) When should you use binary coding instead of numeric allele coding? [1995/03/01] Usually there is no advantage to coding disease loci as either binary or numeric using liability classes. Generally, binary coding is more complex in that we humans often have a hard time thinking that way. Some of the codominant phenotypes lend themselves to binary coding; for example, ABO blood types: A (101), B (011), O (001), AB (111), and unknown (000). Since you cannot distinguish AO from AA at the phenotype level you code both genotypes as (101), presence of A and O. In reality O represents absence of both A and B. However, do not code using (000), since it would be an unknown. Use of binary codes has decreased since DNA markers have come into use since they allow one to type an individual with respect to genotype. You can use binary codes if you have phenotypic data which does not allow for the discrimination of the underlying genotype exactly, and one can code it as the presence with 1 or absence with 0 of factors such as the A and B antigens. Binary codes allow the representing loci with codominant and dominant mode of inheritance, while allele number notation is good only for codominant loci. Few people use binary factor notation. They either use allele numbers for codominant loci, or affection status notation for dominant loci. The main reason why binary factor notation is still currently used is that CEPH's database is in that notation. 4.4) What do you do when allele frequencies not add up to 1, for example, when alleles are not present in a pedigree under study? [1995/03/01] The best approach is to specify n+1 alleles, where there are n alleles actually observed in the pedigree. Use the correct allele frequencies for the n alleles, and for the n+1 allele, use 1 minus the sum of the frequencies of the observed alleles. 4.5) I use LINKAGE and/or FASTLINK, what references should I cite in my papers? [1995/03/01] FASTLINK users should cite: Cottingham, R. W. Jr., Idury, R. M., and Schaffer, A. A. "Faster Sequential Linkage Computations." American Journal of Human Genetics. 53:252-263, 1993. Schaffer, A. A. , Gupta, S. K., Shriram, K., and Cottingham, R. W. Jr. "Avoiding Recomputation in Linkage Analysis". Human Heredity. 44(4):225-37, 1994 Jul-Aug. In addition, all FASTLINK and LINKAGE users should also cite the LINKAGE papers: Lathrop, G.M., Lalouel, J.M., Julier, C. , and Ott, J. "Strategies for Multilocus Analysis in Humans." PNAS. 81:3443-3446, 1984. Lathrop, G.M. and Lalouel, J.M., "Easy Calculations of LOD Scores and Genetic Risks on Small Computers." American Journal of Human Genetics. 36:460-465, 1984. Lathrop, G.M., Lalouel, J.M., and R. L. White. "Construction of Human Linkage Maps: Likelihood Calculations for Multilocus Analysis." Genetic Epidemiology. 3:39-52, 1986. 4.6) What is recoding of alleles all about anyway? [1995/03/01] One of the problems with highly polymorphic markers is that they can increase the computational requirements of the computers by several orders of magnitude due to the large number of alleles present. This can put the computation of some lod scores out of reach for DOS computers and take many days on higher end systems. So it is important to use methods that reduce the number of alleles, and recoding will reduce the number of alleles in your calculations. The method of recoding of alleles described by J. Ott in the Annals of Human Genetics, 42:255-257 (1978) works very well, but can only be done when the mode of inheritance of the disease is known. An article inspired by Ott's original work written M. Braverman in Computers and Biomedical Research, 18:24-36 (1985) extends the recoding of alleles in two ways: 1) it allows for pedigrees of arbitrary structure, and 2) it allows for missing/partially known marker phenotypes. It is usually possible to recode marker alleles to some extent even if the mode of inheritance of the disease is not known since what is still desired with respect to the marker is a labeling which preserves the available information about the source of each marker allele. It is important, however, where the full ancestry of alleles cannot be traced in a pedigree, that the recoded alleles maintain the allele frequencies appropriate to the original alleles. In a complex disorder, this may not be possible. Another method is if the marker in question has 14 alleles in the general population, but only 9 alleles in the study population, it is possible to collapse the functional number of alleles to 9 or 10. Usually, adjust the allele frequencies to sum to 1 by dividing each allele frequency by the sum of the (observed) allele frequencies. For the latter all the allele frequencies remain the same, but the unobserved ones are collapsed into a single allele (and frequency). If there are 9 observed alleles (but there are 14 in the population), then rescaling the frequencies of the observed 9 alleles will also not produce quite correct results. Consider the unlikely example of a huge pedigree with only the most recent generation observed in which the observed 9 alleles all have very low and equal frequency. If there are distantly separated relatives who are affected there is some reasonable support for linkage since the alleles are rare. But if we rescale frequencies to 1/9 per alleles, then sharing of alleles isn't so unlikely. Coding the marker with 10 alleles produces correct results as it will produce the same lod scores as would coding the marker with 14 alleles. 4.7) What do you do when you get thetas greater than 0.5 when using LINKAGE? [1996/22/01] This seems to occur when the GEMINI optimization procedure prefers to go for a local optimum of a theta greater than 0.5 as a result of the starting theta values being to high in a LINKAGE run using ILINK or LODSCORE. This can easily be fixed by modifying the starting theta direclty with LCP or editing the LCP generated script. One can also modify the starting value with PREPLINK or by editing the data file containing allele and disease frequencies. This can be an iterative process and one should change theta values by an order of magnitude until reasonable thetas are obtained. One must also be careful of having intial thetas too low, this can also cause problems in the form of erroneous values. One can also run MLINK to examine what is happening at different thetas to determine the best starting theta. 5.0) COMPUTER ADMINISTRATION AND OPTIMIZATION 5.1) How can I increase the speed of the LINKAGE/FASTLINK package on my workstation? [1995/05/18] 1. Use FASTLINK, which is the C version of the LINKAGE package with a few algorithmic improvements. It can increase the speed of your calculations by an order of magnitude. 2. Setting up lots of paging space, which uses the hard drive as virtual memory (300 megs is usually plenty). Note that paging space is the same as swap space. Then use the "fast" versions of FASTLINK. 3. Use GCC, which is the GNU/Free Software Foundation C compiler, to compile FASTLINK. GCC produces machine language that is about 10% faster than Sun's C compiler. 4. Install the generic small kernel instead of the generic kernel. The generic kernel has device files for almost everything, and can slow the system down. The generic small kernel is configured for a system without many devices and without many users. Installing a generic small kernel is an option during system installation on Sun workstations. 5. Reconfigure your kernel so it has only devices you need. This should give you a small improvement in overall system speed, but if you are already running the generic-small kernel, additional improvement may be so small that it's not worth the trouble. If the generic small kernel is insufficient for your system this step is a must. The generic kernel will slow down your workstation significantly and most of the device support is unnecessary. 6. Don't run your linkage analyses in the background, because running programs in the background gives them a lower priority. Either do the runs in the foreground or you can use the root password to nice the pedin process by -3 to compensate (negative nice values give a higher priority). If you need to log out, you can use the screen command and "detach" a session so you can log out without programs terminating. Later you can log back in and "reattach" the session, which continued to run while you were logged out. The screen command is available at prep.ai.mit.edu and is also on the O'Reilly Unix Power Tools CD- ROM. According to the Sun documentation, nicing below -10 can interfere with the operating system and actually reduce the process' speed. Running them at the standard default level of 0 is usually sufficient. Some people recommend to run a background job to using nice +19 (!). In this way, the job will not interfere with other normal processes like login. 7. Runs with 100% penetrance can run faster than runs with incomplete penetrance. Of course, if you have an unaffected obligate carrier, this won't work. In addition, incomplete penetrance runs may be necessary for your research to be "good". 8. Change the block size of your file system. One can increase performance of a file system by increasing the block size, thus decreasing the number of read-write operations. A block device, such as a hard disk, usually accesses a block of data simultaneously. Thus, if one is expecting to use large files, having large blocks will be an advantage. However, one usually trades the number of bytes lost to partial files since one has to increase the fragment size to a number larger than 1024, for example 2048. That is, each file or part of a file occupies 2048 bytes, a file of 100 bytes will still occupy 2048 bytes. Therefore, bigger blocks give faster bigger blocks with bigger fragments and more lost space. 9. It has been noted that you can increase the speed of programs which create/access large files in the /tmp directory by creating a tmpfs file system. 10. Of course, buying more RAM will increase your speed. It's been said that increasing RAM from 16 to 32 megs will result in a large increase in speed and increasing RAM from 32-64 megs will result in a significant increase. However, increasing beyond 64 megs is not particularly helpful. 6.0) MOLECULAR BIOLOGY ISSUES IN LINKAGE ANALYSIS 6.1) What screening sets are available for linkage analysis? [1995/09/14] For humans there are the Weber lab screening sets: 3, 3A, 4, 4A, 5, 5A, and 6 . Primers for the markers within these sets are available from Research Genetics, both in unlabeled and fluorescent dye-conjugated forms. The information on these screening sets can be downloaded via FTP from dgabby.mfldclin.edu, they are in /pub. EOF From owner-gene-linkage@net.bio.net Sun Jun 30 23:00:00 1996 Path: biosci!agate!newsgate.duke.edu!solaris.cc.vt.edu!homer.alpha.net!uwm.edu!cs.utexas.edu!swrinde!newsfeed.internetmci.com!news2.cais.net!news.cais.net!nntp.primenet.com!uunet!in2.uu.net!newstf01.news.aol.com!newsbf02.news.aol.com!not-for-mail From: cpnintt@aol.com (CPN INTt) Newsgroups: bionet.molbio.gene-linkage Subject: Fungal Genetics - Grant Available Date: 1 Jul 1996 00:45:00 -0400 Organization: America Online, Inc. (1-800-827-6364) Lines: 11 Sender: root@newsbf02.news.aol.com Message-ID: <4r7l4c$ddm@newsbf02.news.aol.com> Reply-To: cpnintt@aol.com (CPN INTt) NNTP-Posting-Host: newsbf02.mail.aol.com We are looking for individuals or research groups who have experience working with fungal genes where you have cloned and expressed fungal genes into industrial hosts ( ie; Aspergillus Sp. ). If you have such experience please feel free to contact us at your earliest convenience. rgds MAE From owner-gene-linkage@net.bio.net Sun Jun 30 23:00:00 1996 Path: biosci!bcm.tmc.edu!cs.utexas.edu!chi-news.cic.net!news.cais.net!van-bc!van.istar!ott.istar!istar.net!news.nstn.ca!coranto.ucs.mun.ca!news.compusult.nf.ca!ts00-p18.remote.nfld.com!redsky From: redsky@public.compusult.nf.ca (Richard A. Vaillancourt) Newsgroups: bionet.molbio.gene-linkage Subject: C1 Esterase Deficiency Date: Mon, 1 Jul 1996 10:28:04 NST Organization: Compusult Limited - Public Access Unix Lines: 11 Message-ID: NNTP-Posting-Host: ts00-p18.remote.nfld.com X-Newsreader: Trumpet for Windows [Version 1.0 Rev B final beta #4] I'm told this is a rare genetic blood enzyme disorder. My first blood work came in as below normal (which triggered the diagnosis) and the second time it came in just above normal. My doctor now seems to have lost interest in my case so I am resorting to the internet for information on the condition and any leads on doctors who maight have special knowledge of or an interest in this condition. In the meantime, I am left with a problem digesting much food (sometime it's as though my chest wall/esphagus just freezes up or becomes paralyzed) , low weight, a white blood cell count that is often below normal, multiple 'supposed' allergies, fatigue, etcetera, etcetera. Amy info would be appreciated. My e-mail address is redsky@nfld.com.