From owner-recombination@net.bio.net Tue Jul 02 23:00:00 1996 Path: biosci!rutgers!sgigate.sgi.com!news1.best.com!nntp.primenet.com!news.cais.net!newsfeed.internetmci.com!swrinde!hookup!news.nstn.ca!newsflash.concordia.ca!news.mcgill.ca!news From: dellaire@odyssee.net (G. Dellaire) Newsgroups: bionet.molbio.recombination Subject: Re:DSB in YEAST Date: 3 Jul 1996 12:58:36 GMT Organization: McGill University Computing Centre Lines: 103 Message-ID: <4rdqps$drh@sifon.cc.mcgill.ca> NNTP-Posting-Host: c-15.das.mcgill.ca X-Newsreader: SPRY News 3.03 (SPRY, Inc.) ---------- > From: Graham Dellaire > To: houston.peter@mail.utexas.edu > Cc: recom@net.bio.net > Subject: RE: Yeast DSB pathway > Date: Tuesday, July 02, 1996 8:35 AM > > > > > > > Peter Houston > > Dept. of > > Chemistry and Biochemistry > > The University > of > > Texas at Austin > > Austin, TX > 78712 > > (512)471-7299 > > > > > > Hello Peter, > > > Associates: > > > > I am a member of Tom Kodadek's group investigating homologous > recombination > > in yeast. Specifically, I am using rad51 protein affinity > chromatography > > to isolate potential members of the DNA double strand break repair > > machinery. I have been anaylizing the elutions from the column with > > antibodies and so far I have pulled out the rad51 and rad54 proteins. I > > feel that this is an exciting result in light of recent identification > of a > > rad54 dependent pathway for double strand break repair in tightly > packaged > > regions of the genome. > By this I assume you are referring to heterochromatin in general or was this more localized, say at the centromere? Interesting .... do you have a reference? I wonder if this is true....i.e. rad54 being involved in recombination at heterochromatin, if this is still some function of accessibility? Meaning that the requirement for rad54 may be a mechanism of increasing accessibility tightly packed DNA to the recombination "apparatus" ? It seems that rad54 is a member of the SNF2 helicase super family of proteins and SNF/Swi 1 are associated with a transcriptional regulation mechanism that uses alteration in chromatin structure to enact replication independent gene expression. Thus it follows this is what you may see here. here is a reference "DNA structure-dependent requirements for yeast RAD genes in gene conversion." Sugawara N. Ivanov EL. Fishman-Lobell J. Ray BL. Wu X. Haber JE. Source/ Nature. 373(6509):84-6, 1995 Jan 5. I work in genome accesibility myself, that is with respect to a recombination mechanism known as one end invasion (Adair et al. 1989, Belmaaza et al 1990, Aratani et al. 1992). > > >Given my recent experimental results, I would like > > to further characterize proteins being retained on my rad51 column. In > > this regard, I was wondering if anyone might supply me with antibodies > that > > you may have for proteins that may interact with the rad51 protein, or > let > > me know of other labs that may maintain such antibodies. Furthermore, I > > would appreciate any advice you might have. > > > > Can't help you with the antibodies... I work in mammalian recombination but good luck... and I am sure someone in the HUGE yeast recombination field can help you out. I hope the size of your peer group though doesn't breed too, too much competition. P.S. Just a stab but why not also try immunoprecipitation approaches, or yeast two hybrid? Also to get over the Ab requirement you might want to produce GST fusions of some of the rad proteins so that they are tagged for easy detection with commercial anti-bodies. Again good luck! G. Dellaire McGill University Experimental Medicine dellaire@odyssee.net http://www.medcor.mcgill.ca/EXPMED/expmed.html From owner-recombination@net.bio.net Wed Jul 03 23:00:00 1996 Newsgroups: bionet.molbio.recombination Path: biosci!daresbury!bioftp.unibas.ch!infobiogen.fr!jussieu.fr!esiee.fr!sgigate.sgi.com!news-res.gsl.net!news.gsl.net!EU.net!usenet2.news.uk.psi.net!uknet!usenet1.news.uk.psi.net!uknet!uknet!bcc.ac.uk!news From: Paul Wells Subject: PRACTICAL INTRODUCTION TO GENETIC ENGINEERING COURSE Message-ID: <1996Jul4.100327.22132@ucl.ac.uk> Date: Thu, 4 Jul 1996 10:03:27 GMT Organization: University College London Lines: 33 A one week practical course designed to teach the basic techniques in genetic engineering will be held from 5-9 August 1996 at the Dept. of Biochemistry and Molecular Biology University College London. A "hands on" approach will enable scientists from higher education and industry, clinicians and research workers who have had no practical experience of recombinant DNA technology to set up such techniques in their own laboratories. Techniques to be covered will include, Southern hybridisation DNA sequencing, PCR, and analysis of cloned DNA using enzyme restriction mapping. Course fee 850 pounds sterling (650 for full time postgraduate students) exclusive of accomodation. Bed and breakfast accomodation for the period of the course can be provided in a local hall of residence for 111 pounds sterling from Sunday 4th August until 10th August. Write for application forms and further details to: Dr. John Ward Department of Biochemistry & Molecular Biology University College London Gower Street London WC1E 6BT Fax: 0171 380 7193 Or e-mail either:- ward@bsm.bioc.ucl.ac.uk p.wells@ucl.ac.uk From owner-recombination@net.bio.net Wed Jul 03 23:00:00 1996 Path: biosci!daresbury!bioftp.unibas.ch!infobiogen.fr!jussieu.fr!esiee.fr!sgigate.sgi.com!news.msfc.nasa.gov!elroy.jpl.nasa.gov!swrinde!cs.utexas.edu!howland.reston.ans.net!Germany.EU.net!zib-berlin.de!fu-berlin.de!news.belwue.de!News.Uni-Marburg.DE!usenet From: "Heinz Rupp, PhD" Newsgroups: bionet.molbio.recombination Subject: VEGF165 cDNA needed Date: Thu, 04 Jul 1996 20:29:55 +0000 Organization: Molecular Cardiology Lab, Div. of Cardiology, University of Marburg, Marburg, http://cardiorepair.uni-marburg.de Lines: 6 Message-ID: <31DC29C3.409B@mailer.uni-marburg.de> NNTP-Posting-Host: pcmf03.med-forschung.uni-marburg.de Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 2.01 (WinNT; I) Hello all: We need very urgently the cDNA of VEGF165. Can anybody please help us? Thank you From owner-recombination@net.bio.net Sat Jul 06 23:00:00 1996 Path: biosci!rutgers!sgigate.sgi.com!nntp.coast.net!news.dacom.co.kr!news.postech.ac.kr!usenet.kornet.nm.kr!agate!dog.ee.lbl.gov!news.cs.utah.edu!swen.emba.uvm.edu!hbeernin From: hbeernin@med.uvm.edu (Hans Beernink) Newsgroups: bionet.molbio.recombination Subject: Re: Yeast DSB pathway Date: 3 Jul 1996 13:15:19 GMT Organization: EMBA Computer Facility, The University of Vermont Lines: 41 Distribution: world Message-ID: <4rdrp7$2ru@swen.emba.uvm.edu> References: <199606302148.QAA07094@mail.utexas.edu> NNTP-Posting-Host: protein.med.uvm.edu X-Newsreader: TIN [version 1.2 PL1] Peter Houston (houston.peter@MAIL.UTEXAS.EDU) wrote: [re: chromatin dependent DSB repair] : I : feel that this is an exciting result in light of recent identification of a : rad54 dependent pathway for double strand break repair in tightly packaged : regions of the genome. Peter- it doesn't seem very surprising (to me) that rad54 strains are deficient in DSBR, especially in regions of DNA structure, as rad54 shows high homology to helicases. The interesting prospect is that Rad52 is absolutely required, even in cases where the putative recombinase, Rad51, is not (check out Sugawara et al. 1995, Nature 373:84). This raises some interesting questions about the roles of Rad51 and Rad52- is Rad52 (and not Rad51) the "general recombinase"? Or is the Rad52 epistasis group functional in chromatin remodeling as well? It's known that Rad51 and Rad52 interact physically (two-hybrid and other suggestive genetics), so I'm a bit surprised that you aren't able to fish out Rad52- or maybe you have, but haven't identified it yet? Best regards, Hans -- _____________________________________________________________________________ "The worst monotonous drone coming from a lectern or the most eye-splitting textbook written in turgid English is nothing in comparison to the psychological Sahara that starts right in your bedroom and spurns the horizon." -Joseph Brodsky, from "In praise of Boredom" delivered as a commencement address at Dartmouth College. _____________________________________________________________________________ Hans T.H. Beernink, Department of Biochemistry, University of Vermont hbeernin@protein.med.uvm.edu FAX (802)862-8229 hbeernin@zoo.uvm.edu Tel.(802)656-8244 From owner-recombination@net.bio.net Sat Jul 06 23:00:00 1996 Path: biosci!rutgers!sgigate.sgi.com!nntp.coast.net!howland.reston.ans.net!vixen.cso.uiuc.edu!newsfeed.internetmci.com!in2.uu.net!news.abs.net!cs.umd.edu!info.usuhs.mil!usenet From: Mika Salminen Newsgroups: bionet.molbio.recombination Subject: Bootscanning for recombination Date: Sat, 06 Jul 1996 15:01:10 -0500 Organization: Henry M. Jackson Foundation Lines: 944 Message-ID: <31DEC605.4D8C@pasteur.hjf.org> Reply-To: msalminen@pasteur.hjf.org NNTP-Posting-Host: 131.158.31.254 Mime-Version: 1.0 Content-Type: multipart/mixed; boundary="------------6A85FA29F3" X-Mailer: Mozilla 3.0b5 (Macintosh; I; PPC) This is a multi-part message in MIME format. --------------6A85FA29F3 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Announcement: The software package for performing "Bootscanning" is now available from our website at http://hivgenome.hjf.org/ "Bootscanning" is a method for detecting recombination in viral sequences. We have only applied it to HIV-1, but it should work for any genes that contain sufficient phylo- genetic signal. You will need GDE and Phylip to run the package, and at the current time, we only provide SUN executables. However, the source-code is also included, so anyone who would care to compile on another system capable of running GDE and Phylip is free to do so. Below is an excerpt from some of the documentation: Bootscanning Package v. 1.0beta1 Principal Idea and Approach: Mika Salminen, msalminen@hiv.hjf.org Design and programming: Wayne Cobb, wcobb@reed.hjf.org (c) 1994-1996: Mika Salminen, Wayne Cobb, Henry M. Jackson Foundation Description: Bootscanning is a method for anaysis of viral recombination. It can be used to compare an unknown, suspected recombinant sequence, to a set of predefined potential parental sequences. It should be independent of organism, but we have only used it for HIV-1 and suspect that it only works for sufficiently variable genes. In the case of HIV-1 there are predefined genetic subtypes which have been called A-H in analyses based on the envelope and gag genes, with the notable exception that the E-subtype does not exist in gag. Viruses with E-subtype envelopes group with the A-type viruses in gag. Bootscanning relies on the alignment of a suspected recombinant sequence with a set of potential parental reference sequences (groups of sequences from the differnt subtypes, or consensus sequences created from sets of reference sequences). After optimal alignment, the alignment is broken into sequential, overlapping segments (or windows) which are fed to a program for phylogenetic analysis (any of the sequence programs of Phylip could be used, we have included menus for three methods). Bootstrapped phylogenetic trees are built for each segment and finally the bootstrap value for placing the unknown with each of the reference sequences/sequence groups is tabulated and plotted along the genome. The assumption is that the unknown will always reach high bootstrap values with it's parental subtypes in windows covering areas of that subtype in the unknown. When a recombination breakpoint is reached, the bootsrap value for one parent+the unknown will go down, and the bootsrap value for the second parent+ the unknown should go up. Therefore we should find the breakpoint in the intersection of the plotted bootscanning lines. Reference alignments of non-recombinant gag and env genes and subtype-reference sequences are included in the package. However, be aware that the B and D-subtypes are sometimes difficult to separate in gag and that the A-subtype in some regions separates to at least 2 subclusters. Therefore we have included consensus sequences A1 and A2 in the cocnsensus alignments. The package contains the following components: Menufile for GDE: "GDEmenus.Bootscan" Insert the menus in this file into your ".GDEmenus"-file. Shell-scripts (place all in /GDE/bin/): "mlbootscan.sh" Performs Maximum Likelihood Bootscanning analysis using SEQBOOT, DNADIST, FITCH and CONSENSE "njbootscan.sh" Performs Neighbor Joining Bootscanning analysis using SEQBOOT, DNADIST, NEIGHBOR and CONSENSE "parsboot.sh" Performs Neighbor Joining Bootscanning analysis using SEQBOOT, DBNAPARS and CONSENSE "analyze.sh" Shell script to run the program analyze. "genchop.sh" Shell script to run the program chop Executables (place all in /GDE/bin/): readseq Fixed sequence format converter. "PhyloMask" Creates masks to exclude gaps (menu available in GDEmenus.Bootscan). "chop" Breaks up masked alignment into individual segments which are created as sequentially numbered input files to the Phylip programs in a subdirectory of your home directory. Each window is numbered at the midpoint of the segment in the alignment. For each segmnet a corresponding outfile and treefile is created which will contain the bootstrap values and the consensus trees. The programs 'analyze' and 'report' are used to extract and tabulate the bootstrap values of specified groups of sequences (taxa or clades). Plotting the tables using the alignment as the x-axis and the bootrap value as the y-axis can be used to identify recombination points. "analyze" Extracts bootstrap values from outfiles. Use analyze.sh to run "report" Collects bootstrap values in tab-delimited table. Attached to this file is also an example of a bootscan-plot of an A/D-recombinant virus. We hope that you will be able to use the method to produce some useful data, and would certainly be happy to hear comments and critique about the package and certainly also bug-reports. We would especially be delighted to here from anyone who has managed to successfully install the package. We also acknowledge that the package is crude and simple, we have not put a lot of effort into getting it very elegant, but it works for us, and we hope that it will for other people, too. We have tried to remove any bugs that have crept up during development, but there will certainly be more. Anyone using the package will do it on their own risk, we take no responsibility for any loss of data or hardware that may result from the use of the package (hopefully there will be none!). Finally, some acknowledgements and disclaimers: This work was supported in part by cooperative agreement N. DAMD17-93-V-3004, between the United States Army Medical Research and Materiel Command and the Henry M. jackson Foundation for the Advancement of Military Medicine, and by grant No. 19191 from the Finnish Academy of Science (Mika Salminen). The views and opinions expressed herein are those of the authors and do not purport to reflect the official policy or position of the US Army or of the Department of Defense. Please refer to the following publications if using the package: Mika O. Salminen, Jean K. Carr, Donald S. Burke and Francine E. McCutchan. (1995). Identification of Breakpoints in Intergenotypic Recombinants of HIV-1 by Bootscanning. AIDS Research and Human Retroviruses, 11, 1423-25. Smith S, Overbeek R, Woese CR, Gilbert W and Gillevet P. (1994) The Genetic Data Environment: An expandable GUI for Multiple Sequence Analysis. Comp Appl Biol Sci, 10, 671-675. Felsenstein, J. (1991). 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Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 1.1N (Windows; I; 16bit) Dear sirs/madam I am wondering if anyone of you knows what happens if you change the direction of an attL-site (lambda-phage) in respect to his attR-site (on the same plasmid) ? Does the excision occur or do some knotted products arise in the recombination ? I would be deeply thankful to you if you could answer me this question or gave me any useful reference. Thanks in advance Igor Kulic From owner-recombination@net.bio.net Wed Jul 10 23:00:00 1996 Path: biosci!rutgers!csn!nntp-xfer-1.csn.net!csn!nntp-xfer-2.csn.net!tali.UCHSC.edu!essex.UCHSC.edu!binstoct From: Teresa Binstock Newsgroups: bionet.molbio.recombination Subject: Gender questions & recombination Date: Wed, 10 Jul 1996 20:01:21 -0600 Organization: University of Colorado, Health Sciences Center Lines: 41 Message-ID: References: <4ru9v4$sia@info4.rus.uni-stuttgart.de> NNTP-Posting-Host: essex.uchsc.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII In-Reply-To: <4ru9v4$sia@info4.rus.uni-stuttgart.de> I posted this response and related questions to two newsgroups: sci.med, sci.bio.misc and thought the recombo newsgroup might generate answers. Medical literature provides examples of XY females in whom SRY (the primary testis-determining gene) is intact. Similarly, there are published studies reporting a number of XX males in whom SRY is not present. Questions I'd like to see answered in these two XX-male types (with SRY, without SRY) and also in XY-females (both the SRY positive and SRY negative types) concern recombination. Generally, in terms of centiMorgans, most XX-female chromosomal segments have a higher rate of recombination than do similar segments of XY-male chromosomes -- and these sexually dimorphic recombination rates occur on autosomes as well as in portions of the X and Y where recombination occurs (ie pseudoautosomal regions in Xp and Xq and Yp and Yq). My questions are: 1. In XX-males and in XY-females, are the various rates of recombination reversed or not? 2. Are germ cells required for such determinations? ******* I've been reading T Shiroishi studies about specific gene-like elements that may be recombined into various parts of the genome and that he and colleagues credit with inducing the sexually dimorphic recombination rates in the chromosomal regions his group has studied. Any comments would be appreciated. Teresa Teresa C. Binstock, Researcher Developmental & Behavioral Neuroanatomy Denver CO USA Teresa.Binstock@uchsc.edu From owner-recombination@net.bio.net Thu Jul 11 23:00:00 1996 Path: biosci!rutgers!news.iag.net!newsfeeder.sdsu.edu!news.uoregon.edu!hunter.premier.net!newsfeed.internetmci.com!news.ac.net!news.bconnex.net!news.abs.net!cs.umd.edu!info.usuhs.mil!usenet From: Mika Salminen Newsgroups: bionet.molbio.recombination Subject: Bootscanning NOTICE! Date: Fri, 12 Jul 1996 13:52:42 -0500 Organization: Henry M. Jackson Foundation Lines: 21 Message-ID: <31E69EF9.61BB@pasteur.hjf.org> References: <31DEC605.4D8C@pasteur.hjf.org> Reply-To: msalminen@pasteur.hjf.org NNTP-Posting-Host: 131.158.31.254 Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 3.0b5 (Macintosh; I; PPC) IMPORTANT NOTICE! Due to an unfortunate mistake the unpublished sequences gag: HO34, HO49, HO42, HO17, E4002, th253, BR025 and UG037 and env: HO34, HO49, HO42 and HO17 were included in the alignments of the "Bootscanning"- package release of July 7, 1996. ( http://hivgenome.hjf.org/ ) THESE SEQUENCES ARE NOT IN THE PUBLIC DOMAIN AND ANY USE OF THEM IS PROHIBITED. PLEASE DELETE THEM FROM YOUR ALIGNMENTS! THEY MAY NOT BE REFERRED TO IN ANY PUBLICATIONS! A new archive will be put together on the server. - Mika Salminen From owner-recombination@net.bio.net Sun Jul 14 23:00:00 1996 Path: biosci!rutgers!oitnews.harvard.edu!hpngsv01.mgh.harvard.edu!helix.mgh.harvard.edu!RUBIND From: rubind@helix.mgh.harvard.edu Newsgroups: bionet.molbio.recombination Subject: whole adult zebrafish cDNA library Date: 15 Jul 1996 03:03:13 GMT Organization: Mass. General Hospital Lines: 9 Message-ID: <4sccdh$2nt@hpngsv01.mgh.harvard.edu> Reply-To: rubind@helix.mgh.harvard.edu NNTP-Posting-Host: helix.mgh.harvard.edu Does anyone know where I can obtain/purchase a cDNA library (either constructed in phage or plasmid) made from whole adult zebrafish? please send the information to: rubind@helix.mgh.harvard.edu thanks, David From owner-recombination@net.bio.net Sun Jul 14 23:00:00 1996 Path: biosci!rutgers!csn!nntp-xfer-1.csn.net!csn!nntp-xfer-2.csn.net!tali.UCHSC.edu!essex.UCHSC.edu!binstoct From: Teresa Binstock Newsgroups: bionet.molbio.recombination Subject: MHC Recombo in TAP1/2, LMP2/7 region. Date: Sun, 14 Jul 1996 19:52:22 -0600 Organization: University of Colorado, Health Sciences Center Lines: 20 Message-ID: References: <31DEC605.4D8C@pasteur.hjf.org> <31E69EF9.61BB@pasteur.hjf.org> NNTP-Posting-Host: essex.uchsc.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII In-Reply-To: <31E69EF9.61BB@pasteur.hjf.org> I've been using Medline extensively and photocopying many articles, many of which are excellent regarding allelic polymorphisms of TAP1 and TAP2 in humans. However, I would very much like to know how to find the most up-to-date data concerning male and females rates of recombination in the MHC region containing the aforementioned human genes. Thank you, Teresa Teresa C. Binstock, Researcher Developmental & Behavioral Neuroanatomy B140 Fragile X Section The Children's Hospital 1056 E. 19th Avenue Denver CO 80218 USA From owner-recombination@net.bio.net Sun Jul 14 23:00:00 1996 Path: biosci!ODYSSEE.NET!dellaire From: dellaire@ODYSSEE.NET ("Graham Dellaire") Newsgroups: bionet.molbio.recombination Subject: RE: MHC Recombo in TAP1/2, LMP2/7 region. Date: 15 Jul 1996 05:24:30 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 58 Sender: daemon@net.bio.net Distribution: world Message-ID: <199607151226.IAA14430@atlas.odyssee.net> NNTP-Posting-Host: net.bio.net ---------- > From: Teresa Binstock > To: recom@net.bio.net > Subject: MHC Recombo in TAP1/2, LMP2/7 region. > Date: Sunday, July 14, 1996 9:52 PM > > I've been using Medline extensively and photocopying many articles, many > of which are excellent regarding allelic polymorphisms of TAP1 and TAP2 > in humans. However, I would very much like to know how to find the most > up-to-date data concerning male and females rates of recombination in the > MHC region containing the aforementioned human genes. > > Thank you, > > > Teresa > Besides scouring all the online journals table of contents.... please see: http://www.medcor.mcgill.ca/EXPMED/DOCS/on-linej.html (I maintain a website here in Montreal) .... you could try to get access to Current Contents it is a little more up to date than Medline. ***************** Don't give up either often you search with some keywords one day and turn up 1 paper then you change a word or ending and get 5 papers the next. That is the problem with the clunky search engines for Medline and C and C. Ultimately, if you want the most up to date information you should be looking for conferences in the area please see: http://www.medcor.mcgill.ca/EXPMED/DOCS/res.html#Conf ..... or even contacting people in the field and asking for recent reprints. Hope this little bit of advice helps, Graham Dellaire McGill Experimental Medicine From owner-recombination@net.bio.net Wed Jul 17 23:00:00 1996 Path: biosci!internet!biosci!not-for-mail From: biohelp (BIOSCI Administrator) Newsgroups: bionet.molbio.recombination Subject: IMPORTANT - BIOSCI Fundraising Update! Date: 18 Jul 1996 02:00:08 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 154 Sender: daemon@net.bio.net Distribution: world Message-ID: <199607180900.CAA23587@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. 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Please contact us at biosci-help@net.bio.net for details. ---------------------------------------------------------------------- From owner-recombination@net.bio.net Wed Jul 17 23:00:00 1996 Path: biosci!bloom-beacon.mit.edu!news-res.gsl.net!news.gsl.net!hunter.premier.net!newsfeed.internetmci.com!netnews.nwnet.net!news.sprintlink.net!news-dc-9.sprintlink.net!news.up.net!news.mtu.edu!not-for-mail From: mjmyers@mtu.edu (Matthew J. Myers) Newsgroups: bionet.molbio.recombination Subject: test Date: 18 Jul 1996 09:53:15 -0400 Organization: Michigan Technological University Lines: 5 Message-ID: <4slfkb$gac@rock.me> NNTP-Posting-User: mjmyers@rock.me.mtu.edu X-Newsreader: TIN [version 1.2 PL2] Ctest test test check one C D C From owner-recombination@net.bio.net Mon Jul 22 23:00:00 1996 Path: biosci!ODYSSEE.NET!dellaire From: dellaire@ODYSSEE.NET ("Graham Dellaire") Newsgroups: bionet.molbio.recombination Subject: FW: Biomedical Job Listings from ExpMed (McGill University) Date: 22 Jul 1996 17:22:53 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 162 Sender: daemon@net.bio.net Distribution: world Message-ID: <199607230027.UAA18311@atlas.odyssee.net> NNTP-Posting-Host: net.bio.net ---------- > From: Graham Dellaire > To: employment@net.bio.net > Cc: recom@net.bio.net;; bioforum@net.bio.net > Subject: Biomedical Job Listings from ExpMed (McGill University) > Date: Monday, July 22, 1996 8:15 PM > > Jobs this Month at ExpMed Job listings: > http://www.medcor.mcgill.ca/EXPMED/DOCS/jobs.html > > > CANADA > > Government > > 1.Environment Professionals, OFFICE OF THE AUDITOR GENERAL > Deadline August 14/96 > > 2.Population Management Biologist (Edmonton, Alberta) > Deadline August 2/96 > > 3.Mycologist (Victoria, B.C.) > Deadline August 12/96 > > Montreal Area > > 1.McGill General > 2 Positions available in the laboratory of Dr. B. > Leyland-Jones > Posted June 25th/96 > > 2.IRCM > HEMOPOIESIS CANCER AND DEVELOPMENT GROUP > Molecular Genetics; Differentiation and Development; Oncology; > Immunology; and Gene Therapy > (post doctoral positions available) > Posted July 3rd/96 > > 1 Position available immediately in the laboratory of Dr. Guy > Sauvageau > POSITION FILLED > > 3.Lady Davis Institute > 1 Position (Ph.D.) in the laboratory of Dr. Prem Ponka > Posted April 9/96 > > 4.Royal Victoria Hospital > 1 Position (Ph.D.) in the laboratory of Dr. Geoffrey Hendy > Posted March 20/96 > > 1 Position (Ph.D.) in the laboratory of Dr. David Goltzman > Posted May 21/96 > > 5.Montreal General Hospital > 1 Position (Post-Doc) in the laboratory of Dr. Guy A. Rouleau > Posted May 4/96 > > Ontario > > 1.Positions at Waterloo University in Biology > > 2.2 tenure track Positions University of Toronto Depts. of > Biochemistry & Medical Genetics and Microbiology > DEADLINE Sept. 1/96 > > 3.3 tenure track Positions University of Toronto Dept. of Medical > Genetics and Microbiology > DEADLINE August 15/96 > > 4.Samuel Lunenfeld Post-Doctoral Fellowship > Samuel Lunenfeld Research Institute, Mount Sinai Hospital > Posted April 26th/96 > > Manitoba > > 1.Positions at the University of Manitoba in Medical Microbiology > > Alberta > > 1.Positions at the University of Alberta > Positions in Biological Sciences > > 2.Several Positions at IntelliGene Expressions, Inc. (Edmonton > Alberta) > Posted July 3rd/96 > > British Columbia > > 1.2 positions: Assistant Professor and Associate/full Professor at > the Biomedical Research Center in Vancouver (UBC) > Deadline:August 31, 1996 > > 2.1 position Catalyx Group Biopharmaceuticals > Posted June 16th/96 > > 3.1 position University of BC Dept. of Microbiology and Immunology > Research Associate > Posted July 3rd/96 > > 4.1 position University of BC Microbiology one year research position > Posted July 3rd/96 > > Outside of Canada > > 1. United States > > 1.Opportunities at the National Institutes for Health, Bethesda > Maryland > +140 postings for postdoctoral positions online, more than 30 > clinical training programs and > all listings support immediate online application. > > 2.Positions at Clontech > > 3.1 Position as Chair of Dept.'s of Biochemistry and Microbiology > University of North Texas > Posted April 4th/96 > > 4.1 Position as Chair of Pharmacology Department > Tulane University, New Orleans, Lousianna > DEADLINE July 15, 1996. > > 5.1 Position Director of Biotechnology Facility > Indiana University (Biochemistry & Molecular Biology) > Posted May 22nd/96 > > 6.1 Position Professor and Chair > Medical College of Ohio (Toledo, Ohio) > Posted May 22nd/96 > > 2. Europe > > Great Britain > > 1.Positions at Cambridge University > Dept. of Biochemistry > Dept. of Pathology > > 2.Positions at the Institute of Biomedical and Life Sciences at the > University of Glasgow, Scotland > Look under "posts available". > > 3.Positions at Imperial College in the Dept. of Biochemistry > > 4.Vacancies at the Institute of Cancer Research London > > 5.Wellcome Foundation Telnet server offering Post-Doctoral and other > listings > Log-on with the password "wisdom" > > 3. Australia > > 1.Positions at the University of Queensland > > 2.Queensland Pharmaceutical Research Institute > > From owner-recombination@net.bio.net Wed Jul 24 23:00:00 1996 Path: biosci!rutgers!csn!nntp-xfer-1.csn.net!csn!nntp-xfer-2.csn.net!tali.UCHSC.edu!essex.UCHSC.edu!binstoct From: Teresa Binstock Newsgroups: bionet.molbio.recombination Subject: Significance of cM sexual dimorphisms Date: Thu, 25 Jul 1996 12:13:55 -0600 Organization: University of Colorado, Health Sciences Center Lines: 54 Message-ID: References: <199607230027.UAA18311@atlas.odyssee.net> NNTP-Posting-Host: essex.uchsc.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII In-Reply-To: <199607230027.UAA18311@atlas.odyssee.net> Quasi-Syllogism with question: 1. Many segments of the human genome have larger cM in females than in males, in some segments there is "equivalence", and in some segments male chromosomes have larger cM. 2. Generally, the cM values are derived from meiotic chromosomes and thus are not indicative of male/female differences in the various chromosomal segments in nuclei cells wherein the chromosomes are not meiotic. 3. ?? Therefore, what is known about causes or causal factors of the cM sexual dimorphisms scattered throughout the genome? 4. The work of Shiroishi and colleagues is the closest I have come to finding an answer to the prior question. They suggest a cis-acting gene that is epigenetically modified by an trans-acting factor, at least in the MHC-region they have perused. 5. The roles of nucleosomal shape, chromatin, and histone acetylation would seem to provide clues as to the cM dimorphisms. If there is sexually dimorphic and epigenetically modified chromatin/histone-acetylation etc in meiotic chromosomes, then there might be a similar chromatin/histone dimorphism in the structure of non-meiotic chromosomes. 6. If such dimorphisms exist in non-meiotic nuclei, then in a most general sense, many genes would have sexually dimorphic accessibility by transcription factors and by other regulatory processes. 7. Many heritable, epigenetic modifications of the genome (eg IGF2/H19 and Prader-Willi Angelmann genes) are known to exist in nuclei of non-meiotic cells. Therefore, if Shiroishi's findings are applicable in other regions of the genome, then those other regions (ie, those that have sexually dimorphic cM in meiotic cells) might also have sexually dimorphic nucleosomes, histones, and chromatin -- which would suggest sexually dimorphic gradations of transcription, etc. 8. Any information about these notions would be appreciated. 9. If there is an error in the above rationale, bringing same to my attention would be most appreciated. Thank you, Teresa Teresa C. Binstock, Researcher Developmental & Behavioral Neuroanatomy Denver CO USA Teresa.Binstock@uchsc.edu From owner-recombination@net.bio.net Thu Jul 25 23:00:00 1996 Path: biosci!ZOOLOGY.UBC.CA!rmyers From: rmyers@ZOOLOGY.UBC.CA (Rik Myers) Newsgroups: bionet.molbio.recombination Subject: Re: Significance of cM sexual dimorphisms Date: 26 Jul 1996 10:40:26 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 69 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net >4. The work of Shiroishi and colleagues is the closest I have come to >finding an answer to the prior question. They suggest a cis-acting gene >that is epigenetically modified by an trans-acting factor, at least in >the MHC-region they have perused. Shioishi and Co. are my sources as well. If I come across anything else, I'll give you a holler. >5. The roles of nucleosomal shape, chromatin, and histone acetylation would >seem to provide clues as to the cM dimorphisms. If there is sexually >dimorphic and epigenetically modified chromatin/histone-acetylation etc >in meiotic chromosomes, then there might be a similar chromatin/histone >dimorphism in the structure of non-meiotic chromosomes. Quite possible, given the work in yeast from Michael Lichten's lab and Alain Nicolas' lab. They (and others) found that recombination hotspots correspond to sites of meiosis-specific DNA double-strand breaks. These breaks co-localize with nuclease hypersensitive domains in chromatin preps from both vegetative (i.e. "mitotic") cells and cells in meiosis. Physiological and genetic perturbations alter the frequency of gene conversion, double-strand break formation, and the exent of nuclease hypersensitivity in parallel. (If you are not familiar with the work, I would be happy to send you refs). Surely some of the sex-specific changes in mammalian gene expression are manifest in both meiotic and non-meiotic tissues. In some of these cases, I would imagine that locus control elements involved in chromatin reconfiguration will be important. The data from yeast (and the MHC in mice, and the B locus in maize, and several fungal genes) support the general model that recombination hotspots are associated with locus control regions. >6. If such dimorphisms exist in non-meiotic nuclei, then in a most general >sense, many genes would have sexually dimorphic accessibility by >transcription factors and by other regulatory processes. This view is gaining recent support in the chromatin literature. There are several recent papers in the fashion plates (e.g. CELL, Genes and Development) on this topic. The genomicists are getting putting together some pretty nifty approaches for examining global patterns of gene expression. Their data will allow us to hone in on chromatin architecture questions in short order. >Therefore, if Shiroishi's findings are applicable in other regions >of the genome, then those other regions (ie, those that have sexually >dimorphic cM in meiotic cells) might also have sexually dimorphic >nucleosomes, histones, and chromatin -- which would suggest sexually >dimorphic gradations of transcription, etc. I don't know about transcription gradients, but gene conversion gradients are likely. I recently suggested to Elizabeth Harris to use gene conversion gradients to identify "promoter regions" in Chlamydomonas. (Tetrad analysis is facile in Chlamy, unlike most other nonfungal euks). Best of luck with your quest. ************************************ * Richard S. Myers * * Dept. of Zoology * * University of British Columbia * * V6T 1Z4 * * TEL: (604) 822-6323 * * FAX: (604) 822-2416 * * EMAIL: Rmyers@bcu.ubc.ca * * * * As of Fall 1996: * * Dept. of Biochem. and Mol. Biol.* * Univ. of Miami School of Med * ************************************ From owner-recombination@net.bio.net Thu Jul 25 23:00:00 1996 Path: biosci!rutgers!news.sgi.com!swrinde!newsfeed.internetmci.com!newsxfer2.itd.umich.edu!portc01.blue.aol.com!newstf01.news.aol.com!newsbf02.news.aol.com!not-for-mail From: honnit@aol.com (HONNIT) Newsgroups: bionet.molbio.recombination Subject: Small peptides and hormone mimicry Date: 26 Jul 1996 12:04:18 -0400 Organization: America Online, Inc. (1-800-827-6364) Lines: 11 Sender: root@newsbf02.news.aol.com Message-ID: <4taqa2$qco@newsbf02.news.aol.com> Reply-To: honnit@aol.com (HONNIT) NNTP-Posting-Host: newsbf02.mail.aol.com In reflection on today's Science article about small peptides and hormone mimicry, I have some questions. I would like to get some opinions and ideas on the process of using small peptides to develop small organic molecules. Is it "pie in the sky"? How real is it? What products do you think will be the most likely candidates? Thanks for your insight!!!!!!!!!!!!!! -HON From owner-recombination@net.bio.net Thu Jul 25 23:00:00 1996 Path: biosci!rutgers!csn!nntp-xfer-1.csn.net!csn!nntp-xfer-2.csn.net!tali.UCHSC.edu!essex.UCHSC.edu!binstoct From: Teresa Binstock Newsgroups: bionet.molbio.recombination Subject: Re: Significance of cM sexual dimorphisms (2) Date: Fri, 26 Jul 1996 10:32:49 -0600 Organization: University of Colorado, Health Sciences Center Lines: 28 Message-ID: References: <199607230027.UAA18311@atlas.odyssee.net> NNTP-Posting-Host: essex.uchsc.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII In-Reply-To: A newly available article raises issues parallel and, to some extent, directly applicable to transcription differences between males and females and how chromatin structure might influence accessibility of transcription factors. These structural differences might be seen (in labs) as differing rates of recombination. au: Rouleus-Bonnin F et al so: Eur J Biochem 238.752-9 1996 ti: Transcription of four satellite DNA subfamilies in Diprion pini (Hymenoptera, Symphyta, Diprionidae). Furthermore, in humans the X and Y chromosomes are extremely sexually dimorphic with regard to alphoid repeat sequences -- which, by affecting intra-nuclear architecture and positioning, might induce or contribute to cM (recombination) differences in pseudoautosomal and telomeric regions. Teresa Teresa C. Binstock, Researcher Developmental & Behavioral Neuroanatomy Denver CO USA Teresa.Binstock@uchsc.edu From owner-recombination@net.bio.net Fri Jul 26 23:00:00 1996 Path: biosci!rutgers!csn!nntp-xfer-1.csn.net!csn!nntp-xfer-2.csn.net!tali.UCHSC.edu!essex.UCHSC.edu!binstoct From: Teresa Binstock Newsgroups: bionet.molbio.recombination Subject: Re: Significance of cM sexual dimorphisms Date: Fri, 26 Jul 1996 18:34:44 -0600 Organization: University of Colorado, Health Sciences Center Lines: 50 Message-ID: References: NNTP-Posting-Host: essex.uchsc.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII In-Reply-To: Much thanks to Rik for his elaborate response, which I found most helpful. By using some of the concepts he presented, I was able via Medline to locate a number of cites that generalize upon the Shiroishi et al findings. Some of those cites I already had, but Rik's explanation created a fine overview, which brought forth additional significance! On one point concerning sexually dimorphic "transcription gradients" that would seem a logical extension of sexually dimorphic cM lengths and their underlying causal factors, I returned to the new Rouleux-Bonnin et al cite (Eur J Biochem 238.752-9 1996) and -- although their focus is not specifically recombination -- their findings, presented amidst a discussion that touches upon chromatin structure and transcription factor accessibility, indicate that "Three satellite DNA subfamilies were transcribed on both strands, and in both sexes. However, the female satellite DNAs seem to be more actively transcribed than those of males, indicating that transcription [of the satellites they were studying] is not constitutive." Teresa suggests that at the level of chromatin structure and access to DNA, the Rouleux-Bonnin et al findings suggest the possibility of sexually dimorphic "transcription gradients" in meiotic and mitotic chromosomes of mammals -- at least in regions having male/female cM differences. Teresa had written: > >Therefore, if Shiroishi's findings are applicable in other regions > >of the genome, then those other regions (ie, those that have sexually > >dimorphic cM in meiotic cells) might also have sexually dimorphic > >nucleosomes, histones, and chromatin -- which would suggest sexually > >dimorphic gradations of transcription, etc. Rik had then responded: > I don't know about transcription gradients, but gene conversion gradients > are likely. I recently suggested to Elizabeth Harris to use gene > conversion gradients to identify "promoter regions" in Chlamydomonas. > (Tetrad analysis is facile in Chlamy, unlike most other nonfungal euks). Teresa Teresa C. Binstock, Researcher Developmental & Behavioral Neuroanatomy B140 Fragile X Section The Children's Hospital 1056 E. 19th Avenue Denver CO 80218 USA From owner-recombination@net.bio.net Mon Jul 29 23:00:00 1996 Path: biosci!IMMAG.MCG.EDU!moshe From: moshe@IMMAG.MCG.EDU (Moshe Sadofsky) Newsgroups: bionet.molbio.recombination Subject: Post-Doc, V(D)J recombination Date: 30 Jul 1996 09:23:40 -0700 Organization: MCG Lines: 19 Sender: daemon@net.bio.net Distribution: world Message-ID: <31FE4598.6223@immag.mcg.edu> Reply-To: moshe@immag.mcg.edu NNTP-Posting-Host: net.bio.net Moshe Sadofsky is setting up a new lab at the brand-new Institute of Molecular Medicine and Genetics at the Medical College of Georgia, Augusta Ga. I need one or two post-doctoral researchers to start with, for continuing studies of the RAG genes and the molecular biology of this recombination system. See the group advertisement in Science 273 July 5, Œ96, p. 144. Please pass this information along to potential candidates. CONTACT:Moshe Sadofsky MCG-IMMAG CB-2803 Augusta GA 30912-2650 Phone : 706 721-8761 Fax number: 706 721-8752 e-mail: moshe@immag.mcg.edu From owner-recombination@net.bio.net Tue Jul 30 23:00:00 1996 Path: biosci!ODYSSEE.NET!dellaire From: dellaire@ODYSSEE.NET ("Graham Dellaire") Newsgroups: bionet.molbio.recombination Subject: RE: Significance of cM sexual dimorphisms Date: 31 Jul 1996 16:13:32 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 110 Sender: daemon@net.bio.net Distribution: world Message-ID: <199607312317.TAA29581@atlas.odyssee.net> NNTP-Posting-Host: net.bio.net ---------- > From: lichten@helix.nih.gov (Michael Lichten) > To: recom@net.bio.net > Subject: Re: Significance of cM sexual dimorphisms > Date: Wednesday, July 31, 1996 11:56 AM > > I am enjoying reading this discussion! Just a couple of comments: > > 1. The most prominent sexual dimorphism in humans and mice is in then > terminal localization of crossovers. In male meiosis, a significant class > of crossovers are telomeric or sub-telomeric; in females, they are more > "uniformly" distributed. The best data for this is from Hulten's group > (Chromosoma 104:223-7 and 104:308-14, which look at chiasmata > localization. I have heard that the mouse mapping data is also consistent > with this notion, or at least is becoming more so as more terminal markers > emerge. > Hello all, A recent paper in PNAS by a group in China (April 1996, vol 93 pp 2795-2800) showed that telomeric sequences located terminally were associated with smaller loops of DNA (loop domains) vs. telomeric sequences found interstatially. the work was done in wild and transgenic mice Thus packing of similar sequences can differ based on relative location along the chromosome. The authors suggest that high recombination rates at the telomeres of mice and humans correlates with shorter loop lengths and this "somehow" may provide an idea of a mechanical basis for the phenomenon.... Well shorter loops of DNA might mean that the DNA is more highly constrained topologically and perhaps a more likely to be nicked or have double strand breaks (either due to strain or as being a better substrate for topoisomerase etc). Alternately, to be the devils advocate, their observation seems a little paradoxical. Tighter packaging, i.e. smaller loops, would mean less accessibility to proteins involved in recombination. Apparently this is not the case! For sometime now various groups have proposed that the nuclear matrix plays a central role in DNA metabolism. Perhaps having smaller loops of DNA could mean greater access to proteins within the matrix. Topo II isomerase is a major component of the matrix and is a good candidate for an initiator of recombination. Transcripition for instance has been hypothesized to occur at the borders of chromosomal domains (Cremer et al. 1993) and that active genes are found closer to the matrix (Ward and Coffey, 1991 also see a really attractive Channel Model of Nuclear Structure by Razin and Gramova in Bioessays (vol17 (5), 1995)). Perhaps too, recombinationally active DNA is associated with the matrix. >2. It's important to separate the issue of transcription from that of >chromatin structure. All available data (from studies of HIS4 and ARG4, >also some of our unpublished studies) indicate that it's chromatin >openness rather than transcription per se, and that TATA box deletions >that greatly depress transcription need not affect gene conversion or DSB >frequencies. I agree about the openness of chromatin vs. transcription. Mere enhancer binding may be sufficient for increase in recombination (look to the immunoglobin class switch for examples). Enhancer binding doesn't necessarily require the TATA and its deletion seems to be a nice way to decouple transcription and "openess" caused by enhancers etc Transfection experiments in mammalian cells have shown that efficiency of recombination with a transgene can be increased when the DNA is actively transcribed (Thomas and Rothstein, Cell (56) p. 619, 1989 and Nickoloff and Reynolds MCB p. 4837, 1990). It would be interesting to hypothesize that the DNA loops would be smaller over the region containing the transgene when it is transcribed. Indeed when I think of it there are many examples of tissue specific changes in chromatin that correlate with transcription of a gene (look at LCR control of betaglobin locus Wijgerde et al. 1995 in Nature (377) p. 209). Also there are examples in which matrix attatchment regions (MARS)depended on the transcriptional state of a gene ( see the chicken alpha globin gene Farache et al. 1990 in MCB p 5349). A model being that you have structural MARS and transient MARS which depend on the transcription or replication state of the locus. YES even replication of DNA is intimately involved with the nuclear matrix (DNA pol alpha and topo II are found in high concentration in the matrix and Cook and Jackson at Oxford have some very nice models of Replication factories which may be anchored to the matrix.... see Jackson (1995) in Bioessays (vol 17 no. 7 p.587) and Cook (1991) Cell (66) p 627.). I think the matrix is probably not rigid and not a skeleton as most people image it. Read Razin and Gramova's Channel Model.... nice rationale against the skeletal model of chromatin structure. Besides not only do you have to replicate DNA in S phase you have to replicate chromatin and the matrix! Makes far more sense if the matrix is emorphous and easily dissassociated during replication of DNA. So to sum up Transcription, Replication and Recombination all seem to have a great deal in common with respect to accessibility and the nuclear matrix. Cheers... I am looking forward to any and all replies, Your friendly Neighborhood Discussion leader Graham Dellaire Experimental Medicine McGill University dellaire@odyssee.net From owner-recombination@net.bio.net Tue Jul 30 23:00:00 1996 Path: biosci!ODYSSEE.NET!dellaire From: dellaire@ODYSSEE.NET (Graham Dellaire) Newsgroups: bionet.molbio.recombination Subject: Question: A centimorgan (cM) .is how many Kilobases? Date: 30 Jul 1996 21:08:51 -0700 Organization: McGill Div. of Experimental Medicine Lines: 15 Sender: daemon@net.bio.net Distribution: world Message-ID: <31FEDC0A.2DF9@odyssee.net> NNTP-Posting-Host: net.bio.net Hello all, I have forgotten the conversion for cM distances in the average mammalian genome. Does anyone remember the number of kb in a cM? Thanks in advance.... this is really bugging me (hehe) Graham Dellaire McGill University dellaire@odyssee.net From owner-recombination@net.bio.net Tue Jul 30 23:00:00 1996 Newsgroups: bionet.molbio.recombination Path: biosci!lhc.nlm.nih.gov!nih-csl!NewsWatcher!user From: lichten@helix.nih.gov (Michael Lichten) Subject: Re: Significance of cM sexual dimorphisms Message-ID: Sender: postman@alw.nih.gov (AMDS Postmaster) Nntp-Posting-Host: 128.231.218.92 Organization: LB/DCBDC/NCI References: Date: Wed, 31 Jul 1996 15:56:17 GMT Lines: 46 I am enjoying reading this discussion! Just a couple of comments: 1. The most prominent sexual dimorphism in humans and mice is in then terminal localization of crossovers. In male meiosis, a significant class of crossovers are telomeric or sub-telomeric; in females, they are more "uniformly" distributed. The best data for this is from Hulten's group (Chromosoma 104:223-7 and 104:308-14, which look at chiasmata localization. I have heard that the mouse mapping data is also consistent with this notion, or at least is becoming more so as more terminal markers emerge. It seems unlikely to me that sex-specific differences in gene expression could account for such a systematic difference. Instead, I would suggest that in species such as mice and men, there's selective presssure to create a mechanism to ensure a terminal concentration of crossovers in the heterogametic sex--for the very reason that one needs to ensure a crossover in the pseudoautosomal region. Kind of the tail wagging the dog, but that's the way it often is. However, one has to be careful then about what's going on in interstitial regions, because once one has a terminal crossover, interference effects are going to further change the pattern of crossovers on the rest of the chromosome. Also, the presence of internal telomeric sequences, the relics of previous rearrangements, might also contribute to differences in the pattern of crossovers in males and females--see Ashley & Ward, Cytogenet Cell Genet 62:169 for an example. One should also remember that most of the intervals that are being looked at are very large, too large to be conceivably affected by a change in expression in a specific gene or a gene cluster. Certainly the MHC data is an exception to this statement, but there's no evidence in that case that there are differences in gene expression, etc. I don't mean to say that changes in chromatin/chromosome structure associated with sex-specific patterns of gene expression are _not_ responsible for some of the map differences we see. I just think that there are other mechanisms possible, in fact, likely. 2. It's important to separate the issue of transcription from that of chromatin structure. All available data (from studies of HIS4 and ARG4, also some of our unpublished studies) indicate that it's chromatin openness rather than transcription per se, and that TATA box deletions that greatly depress transcription need not affect gene conversion or DSB frequencies. Thanks for the stimulating discussion! -- Michael Lichten lichten@helix.nih.gov