Miscellaneous Genome Information

Interested parties may want to join mappers@iastate.edu and and/or angenmap@iastate.edu list servers. Send email to to get on their lists.

Selective Genotyping

Lander Botstein (1989) Genetics: 185-99.
Darvasi and Soler (1992) TAG 85: 353-359.
Darvasi and Soller (1994) Genetics 138: 1365.
Michelmore et al. (1991) PNAS 88: 9828.
Olson and Wijsman (1994) Am J Hum Genet 55: 574-580.
Tanksley (1993) Ann Rev Genet 27: 205-233.
X400-Received: by /PRMD=Iris/ADMD=Mensatex/C=Es/; Relayed; Tue,  5 Sep 1995 12:18:45 UTC+0200
X400-Received: by /PRMD=es/ADMD=Mensatex/C=es/; Relayed; Tue,  5 Sep 1995 12:18:32 UTC+0200
Date: Tue,  5 Sep 1995 12:18:32 UTC+0200
X400-Originator: enciso@etseal.upc.es
X400-Recipients: non-disclosure:;
X400-Content-Type: P2-1984 (2)
X400-Mts-Identifier: [/PRMD=ES/ADMD=/C=/;950905121832]
Content-Identifier: 954
Conversion: Prohibited
From: Miguel Perez Enciso 
To: 
Message-Id: <954*/S=enciso/OU=etseal/O=upc/PRMD=iris/ADMD=mensatex/C=es/@MHS>
Subject: Bulked DNA
Mime-Version: 1.0 (Generated by Ean X.400 to MIME gateway)

Some authors (Michelmore et al., 1991, PNAS 88:9828; Darvasi and Soller, 1994,
Genetics 138:1365) have proposed the use of DNA pooling of extreme individuals 
for reducing costs of genotyping in order to detect markers linked to qtls.
Darvasi and Soller suggest that quantitative densitometry of allelic bands
can be used to estimate the frequency of the marker allele in the pool.
How accurate is this technique? I pressume that its precision will decrease
rapidly as the number of pooled dnas increase. There can also be problems
with unequal amplification. Has anyone used this technique
extensively?
Thank you for your comments!
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Miguel Perez-Enciso                   Phone: 34-73-702500 ext 5110
Area of Animal Production             Fax: 34-73-238301
UdL-IRTA                              email: enciso @ etseal.upc.es
Rovira Roure 177
25198 Lleida, Spain
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Date: Tue, 12 Jul 1994 09:13:45 +0100 (CET)
From: Sijne.vanderBeek@alg.vf.wau.nl
Subject: Major and Minor Genes

With Holland out of the World Cup, I have time to do some reading again. In a 
mini-review of JM Cheverud and E Routman (J.Evol. Biol 6:463-480, 1993) I 
read: "... These genes have been referred to as polygenes and are not likely 
to be a separate class of gene loci but rather the minor alleles at the same 
loci as alleles of major effect (Pedersen and Berg, 1988; Edwards et al, 
1992)........." 

My question is: is there much evidence for this hypothesis in animals or 
plants. If so, we really should not do any association/mapping study within a 
population but focus on (making) crosses between extremely different 
lines/populations. A question to Leif, Chris or et al: Did you already try to 
use your markers of chromosome 4 to see if they are explaining variance 
within a single breed or are you planning research on this?

Sijne van der Beek
Department of Animal Breeding
Wageningen Agricultural University
P.O.Box 338
6700 AH Wageningen
The Netherlands

Date: Wed, 13 Jul 1994 11:29:29 +0100
From: CHRIS HALEY 
Subject: Big ones and little ones

The evidence there is comes mainly from plant studies, where QTLs seem to map 
to regions where known major genes are located. The suggestion that detectable 
QTL might be 'lesser' alleles at loci with known alleles of very major effect 
seems to been made (or revived at any rate) by DS Robertson (J. Theor Biol. 
117 1-10, 1985) and is supported by the studies of Edwards et al and others 
referred to by Sijne. Of course, with a number of known major loci affecting 
plant height, for example, and a number of QTL mapped in any study somewhat 
imprecisely, it is not surprising that coincidences in position are found. So 
more data are needed and ultimately we may need the molecular basis of alleles 
at the same locus causing major and minor effects before we are fully 
convinced. This evidence is likely to come from plants and model species before 
livestock, but nonetheless I think that Sijne has a point in indicating the
additional value that the Robertson hypothesis gives to crosses between extreme 
lines (of course I would, as this is a large part of the research we are 
involved in). We have already used this arguement (see e.g. Brascamp et al. - 
not yet published, but you should not have any trouble getting a copy Sijne) 
and if we were looking within or between commercial pig breeds, chromosome 4 
would be one focus. Is anyone out there daring to do a dairy x beef cross and 
look at regions where believable QTL have been located within Holsteins and 
then going back into Holsteins to look at the additional regions where QTL have 
been located in the cross?

As to John's alternative scenarios, I would vote for a bit of all three of them 
(sitting on the fence as usual). I don't think we should abandon the 
infinitesimal model just yet either - we know it is wrong  but it may be more 
right than than anything else we have as yet. Just as the Dutch should not have 
given up playing under the mistaken belief that the referee had not abandoned 
the offside rule....

Email : Chris.Haley@AFRC.AC.UK                   Roslin Institute (Edinburgh)
Tel.  : + 44 31 440 2726                         Roslin, Midlothian
Fax   : + 44 31 440 0434                         EH25 9PS, U.K.

Date:         Tue, 07 Dec 93 13:18:42 MEZ
From: Henner Simianer 

Dear genemappers, actually I wanted to send this message to
Joel Weller, but maybe the question is of general interest,
so I put it on the network. It is about selective genotyping.
The idea has been brought forward to reduce the number of
individuals necessary to genotype (in QTL detection) by typing
only phenotypically extreme individuals (see eg. Weller and
Wyler, TAG 83:582). This has been done here: highest and lowest
protein producing cows have been genotyped for milk protein
polymorphisms. There are different genotype frequencies in
the two groups, which may be interpreted as an indication of
linkage. But is there any possibility to eg. estimate QTL effects
>from such data. Or even more: can we do any sensible statistics
with such data, since one of the basic assumptions of virtually
all statistical procedures, i.e. random sampling from a
certain distribution (not necessarily normal) has been violated.
Maybe mixture models would be adequate (?)
Thanks for any comment   Henner Simianer

Dr. Henner Simianer
Department of Animal Husbandry and     > Institut fuer Tierhaltung
Animal Breeding                        > und Tierzuechtung
Animal Genetics Group                  > Fachgebiet Haustiergenetik
University of Hohenheim (470/HG)       > Universitaet Hohenheim (470/HG)
D-70593 Stuttgart
Telephone:  +711/459-3007 or -3006
Telefax:    +711/459-3290

From: weller@aipl.arsusda.gov
Subject: selective genotyping
Date: Tue, 7 Dec 1993 09:45:13 -0500 (EST)

Dear Henner Simianer,
    I saw your note, and am aware of the problem, but I can't help you much.
Most of the literature dealing with selective genotyping has dealt with its
power to detect effects of a given magnitude.  My 1992 paper in TAG was an
exception.  The general wisdom has been once selective genotyping has been
used to detect effects, then go back and take a random sample of the
population to get unbiased estimates of the effects.  Nearly all studies that
have attempted to estimate QTL effects have assumed an underlying normal
distribution for the sample, which would not be true in this case.  This of
course is not required, but does make life easier.  Christine Hackett and I
recently completed a study on QTL estimation for discrete characteristics,
and the results look good, based on the EM method of Jansen (1992, TAG 85,252).
This method does not require you to assume a normal distribution.  He for
example considers an exponential distribution, which is not too different
from a truncated normal distribution.  I hope this helps.
                                Joel Weller
  On sabbatical with AIPL, E-mail:  weller@aipl.arsusda.gov

Date: Tue, 07 Dec 1993 16:19:01 +0100 (CET)
From: Sijne.vanderBeek@alg.vf.wau.nl
Subject: selective genotyping

Lander and Botstein (1989;genetics 121) suggest that selective genotyping 
will not influence your estimates as long as you include the phenotypic
information on all animals and treat the genotypes of untyped animals as 
missing. If you did a within family selection of extreme individuals and
want to estimate the effect of a QTL linked to your protein genes, then you 
are probably allright if you use a ML routine and include all data. I do not 
know if this is also true in case you want to estimate a direct gene effect 
together with a effect of a linked QTL. I'm afraid I've no results to backup 
my comments.

Date: Tue, 7 Dec 93 10:46:23 -0600
To: angenmap@iastate.edu
From: gianola@calshp.cals.wisc.edu
Subject: Selective genotyping

I enter this discussion on selective genotyping with trepidation as
this is not my cup of tea. However, theoretically, what van der Beek says
seems right, provided that selection is "ignorable" in the sense of Little
and Rubin (Statistical analysis of missing data, Wiley).
 
There are situations in which one can write the likelihood as if selection
did not occur,  and the maximizer of the likelihood can be found ignoring
selection--provided all data are included in the analysis, as van der Beek
suggests.

However, it is not generally true that the sampling distribution of the
maximum likelihood estimates is the same with than without selective
genotyping; in other words, one must be careful with significance tests.

From a Bayesian perspective, the posterior distributions would be
unaffected, provided all data upon which selection was based are included
in the analysis.

I would also like to point out that it is not only a matter of "including
all data" in the analysis. Likelihoods and posteriors must be written
correctly, e.g., relationship matrices or appropriate coancestries must be
specified.

Some useful references are perhaps Im et al. (Genetics, Selection,
Evolution, 1989), Gianola et al. (Genome 31: 768-777) and Gianola and
Fernando (Journal of Animal Science 63: 217-244).

Date: Wed, 08 Dec 1993 17:10:00 +1300
From: Ian.Hermans@vuw.ac.nz
To: angenmap@iastate.edu
Subject: selective genotyping

To add more confusion to the discussion on selective genotyping....
What statistical analysis should be applied to a DNA fingerprint band which appe
ars to segregate with a multi-allelic trait on the basis of selective genotyping
 of extremes? Analyses have been within a single, large half-sib family (170 off
spring). Any advice?

Ian Hermans
School of Biological Sciences
Victoria University of Wellington
Wellington, New Zealand

Three Point Mapping

Date: Wed, 13 Oct 93 09:37:58 CST  
From: "Roger Shanks" 

I would like to incorporate information on a three-point linkage study
with animals in my introduction to genetics course.   Do any of you have
suggestions on what three loci would work well?

Date: Wed, 13 Oct 93 12:25:44 -0500
From: rodrigue@calshp.cals.wisc.edu

These references (which include examples) could be useful for you:

Three-Locus Systems Impose Additional Constraints on Pairwise Disequilibria.
Robinson W. P. et al., (1991). Genetics 129:925-930

Selection hitchiking and disequilibrium analysis at three
linked loci with application to HLA data.
Robinson, W. P. et al., (1991). Genetics 129:931-948

Date: Thu, 14 Oct 1993 10:29:16 +1000
From: Bill Barendse 

I think FSH, HBB, and PTH would be good from chr 15 in cattle since they
are close and several polymorphisms have been generated for each.

Also CYP21, BoLA DR, and PRL which are close and several polymorphisms on
bovine chromosome 23 have been generated.
Date: Tue, 26 Feb 91 09:16:47 -0600
From:	DIN::"BIOSCI-REQUEST@genbank.bio.net" 26-FEB-1991 06:55:33.15
To:	human-genome-program@crc.ac.uk
Subj:	Combining 2-point data

The problem is simple: how much evidence can we adduce for the regional
localisation of e.g.  a disease gene based on linkage data using a
number of other markers? This must be commonly addressed, but I don't
seem to be having much luck with the literature. 

One approach: do a full multipoint analysis e.g. with LINKMAP to provide
a location score. This is limited with polymorphic markers and large
families to say three markers + the disease gene. What can I do with the
data from the other nearby markers which I cannot include in the
analysis? Or do lots of multipoints using different subsets of markers -
but each time I am only using some of the available information, and
anyway which of the multipoints should I "trust" to be giving the
"correct" answer?

Other approaches would in general look at some way to combine all the
two-point data, but which is the best way and what is the strength of
the evidence thus obtained? I looked at the paper by Olson and Boehnke
(Am J Hum Genet 47:470-482, 1990) comparing different algorithms to
order the markers, but this did not really tell me much about the degree
of evidence that the disease gene was or was not linked to a group of
markers known to be linked to each other.

Morton and Andrews, in their paper on MAP (Ann Hum Genet 53:263-269,
1989), describe how they order loci and then say that "Global support
for a locus expresses the evidence on chromosome assignment as sigma
Z(thetaE) where thetaE is the recombination rate expected between the
locus and another marker on the chromosome, and the summation is over
all syntenic markers.  Although the lods from the same data set are
dependent, this has remarkably little effect on significance levels."
This sounds like exactly what I need, except I cannot believe that it is
correct.  If I understand what they are saying it is that having found
the best position for the markers and disease locus I can calculate
global support for the disease locus being linked to the other markers
by summing the lod scores of the disease locus with each of the other
markers at the distance which separates them on the new map.  It seems
to me that this could easily give a large overestimation of the global
support, and I think their second sentence is incorrect - I think that
the fact that the data are dependent could have a large effect on
signicance levels.

I believe Edwards mentioned this point in a letter to Nature in 1989
(although as he was writing in the context of a multipoint analysis I
did not agree with him entirely). If we had a small family and a highly
informative (in fact say completely informative) marker which gave a
small positive lod score with a disease at a certain distance, then we
would expect that if we studied another extremely informative marker in
the same family which was tightly linked to the first (in fact say
another polymorphism of the first) then we would get the same positive
lod score at the same distance. So we know that studying the new
polymorphism would (if I have understood Morton's approach correctly)
double the lod score. But clearly we have not doubled our evidence in
favour of linkage, which still stands where it was before.

Intuitively, the closer linked and more informative are two markers, the
less independent information one gives over and above the information
from the first. What are people's views on this subject - as I say it
must be a common problem. How can we best utilise data from all markers
to judge the extent of evidence in favour of disease gene being located
approximately in a particular region?

Dave Curtis

Academic Department of Psychiatry,    Janet:       dc@UK.AC.UCL.SM.PSYCH
Middlesex Hospital,                   Elsewhere:   dc@PSYCH.SM.UCL.AC.UK
Mortimer Street, London W1N 8AA.      EARN/Bitnet: dc%PSYCH.SM.UCL@UKACRL
Tel 071-636 8333 Fax 071-323 1459     Usenet: ...!mcsun!ukc!mrccrc!D.Curtis

Sex Differences in Mapping

Date:         Wed, 20 Oct 93 11:31:37 MEZ
From: Henner Simianer 
To: ANGENMAP@iastate.edu

Dear genemappers: I hope you excuse a strange question of an oldfashioned
quantitative geneticist. As far as I have understood the biological
basics, there seems to be a quite evident difference in recombination
rate between sexes with the heterogametic sex showing lower recombination
frequency. There also seems to be some evidence of further environmental
effects (e.g. of age) on the recombination rate.
I have now a couple of questions with regard to that:
Is there any idea, why this mechanism is sex dependent? Does it have a
biological function?
Is there any confirmed evidence of sex differences in recombination rate
in farm animals?
Do the mapping projects account for these potential sex differences
in their design? Is it taken into account when analyzing the data?
Are there any key references referring to these aspects in farm
animal genome analysis?
Thanks in advance for any comment   Henner Simianer
======================================================================
Dr. Henner Simianer
Department of Animal Husbandry and     > Institut fuer Tierhaltung
Animal Breeding                        > und Tierzuechtung
Animal Genetics Group                  > Fachgebiet Haustiergenetik
University of Hohenheim (470/HG)       > Universitaet Hohenheim (470/HG)
D-70593 Stuttgart
Telephone:  +711/459-3007
                    -3006
Telefax:    +711/459-3290

From: weller@aipl.arsusda.gov
Subject: effects on recombination rate
Date: Wed, 20 Oct 1993 08:55:02 -0400 (EDT)

With respect to effects on recombination rate, I just discussed this
question in detail with Harris Lewin at Illinois.  Most of us grew up
assuming that recombination rates are written in stone.  This of course
is not the case, but was due mainly to the difficulty of estimating
effects of various factors on recombination rates.  Now with the ability
to do single sperm cell PCR it is possible to estimate recombination
rates for individual sires, and as you noted, recombinations rates are
different for the two sexes, and for different individuals.
     This gives us the interesting option to
use one sex for gross mapping (a telescope), and the other sex for fine
mapping (a microscope).  I don't know of any published references.  You
may also try to contact Abram Korol at the University of Haifa, Israel,
who is also very interested in this question.  I don't have an E-mail,
but the phone number is:  972-4-240460.
                           Joel Weller
                           AIPL, Beltsville, MD

From: BLOOD%UIUCVMD@isumvs.iastate.edu
Date: 20 Oct 1993 09:05:08 CDT

1.  Increased recombination seems to be the property of the homogametic
sex.  In birds, males show an extended linkage map.  As for
biological function, it would seem advantageous to increase
recombination (at least from an evolutionary perspective).  Why this is
sex-determined is anyone's guess.

2.  For cattle, we have data indicating recombination differences
between the sexes, with females the sex showing greater frequency.  This
is from direct comparison of sperm typing data with oocyte/polar body
typing in females.  We will be submitting a manuscript on this subject
within the next few weeks.  The data will probably be presented in Oslo
at the meeting on Comparative Gene Mapping.  (Anyone who has not
received info on this meeting and would like to get it please let me
know).

3.  We have even found significant differences between bulls for
recombination rate between two loci.  Obviously, this has very important
implications.A manuscript describing this work is also in preparation.

4.  Our mapping work is with paternal half sib families so our map will
be male specific.  Other maps generated with full sib families will have
sex-specific and sex averaged maps.  It will be interesting to compare
these maps when all the data are available.

Harris Lewin
University of Illinois

Date: Thu, 21 Oct 1993 11:07:01 +1000
From: Bill Barendse 
Subject: sex specific theta

With regard to sex specific recombination rates there is documented 
evidence of sex differences in recombination rates for cattle chromosome 
21 in a paper (Barendse et al.) which will appear in Genomics in 
December 93.  However, the overall difference between the maps is 
of the close order of female = 1.2 x male length, different to that 
found in other mammalian species.  These differences are not only in one 
direction, i.e., near the telomere the male map is longer than the female 
map while the female map is longer near the centromere.   There is no 
evidence in humans that such a pattern is consistent over all chromosomes
and it will be interesting to see if there is any consistency in cattle.

There is no a priori reason why the recombination fractions should be 
similar in the two sexes since meiosis occurs in different tissues.
What is of more interest is to determine whether there are exceptions 
to Haldane's 'Law' that the heterogametic sex has a shorter genetic map.

It is clear that recombination is not always advantageous to the organism.
If there are linked loci in which the alleles are coadapted then selection
will act to maintain the linkage disequilibrium and recombination may be 
disadvantageous.  One area of interest is in BoLA and its surroundings 
where we have measured large differences in recombination rates between 
bulls and cows (submitted manuscript).  Indeed, if recombination were
an unadulterated good then there would be clear selection for an increase
in numbers of chromosomes during evolution.  There is evidence of
increases and decreases in chromosome number as well as in NF. 
Bearing this in mind, it would be interesting to determine whether the
regions of differential imprinting of parental genomes corresponds to
differences in recombination fractions in the sexes. 

With regard to the construction of the cattle genetic map the map is 
separated into sex specific recombination fractions as a matter of course.

From: Christopher Moran 
Date: 	Thu, 21 Oct 1993 09:20:05 +1000
Re: Sex differences in recombination rate

My colleague, Dr Rory Hope, from the dept of Genetics at the University
of Adelaide in South Australia has been studying recombination rates
in a small marsupial mouse called Sminthopsis crassicaudata. The are enormous
differences in recombination frequency between males and females in
this species, but unlike the situation in other mammals, males have a
high recombination frequency and females have a low frequency. Thus loci
which show recombination frequencies of the order of 30 to 40% in males
will show 0% recombination in females. Cytologenetic analysis of female
meiosis has shown that all chiasmata are terminally localised, whereas
many interstitial chiasmata are found in males. This is apparently the most
extreme example of recombination differences between the sexes in mammals, but it is the homogametic sex with the low frequency.

In relation to birds, a far as I am aware there is no evidence of sex differences in recombination frequency. So I don't think that explanations in terms
of heterogametic versus homogametic, or even in terms of maleness versus
femaleness, can be universally found. I suspect that each case must be
treated on its merits and given the differences between individuals
which Harris Lewin has documented, this is not surprising.

Chris Moran
Associate Professor in Animal Genetics
Dept of Animal Science
University of Sydney, NSW 2006

From: BLOOD%UIUCVMD@isumvs.iastate.edu
Date: 21 Oct 1993 09:40:33 CDT
RE: Sex differences in theta

There are other exceptions to the rule about the homogametic sex having
the longer map.  For example, see Fang and Jagiello, Biol. Repro.
45:447, 1991 (the Turkish hamster).  Interesting data on fish show
that hormonal reversal of male fish leads to an increase in crossing
over!  There are few absolutes in biology.

Recombination within the MHC is a special case.  There are also
recombination hot spots between genes within the MHC and even apparently
within exons (e.g., exon 2 of HLA-DRB1).  Of course, all recombination
events cannot be advantageous.  However, recombination
remains an essentially important mechanism of evolution.

It is interesting to note that our data agrees with Bill's on the MHC.  That's
where we have found within and between sex differences in recombination rates.

Harris Lewin
University of Illinios

Date: Thu, 21 Oct 93 11:11:11 -0500
To: angenmap@iastate.edu
From: gianola@calshp.cals.wisc.edu
Subject: VARIABILITY IN RECOMBINATION RATE

The discussion so far suggests that there are "clear" differences
in recombination rates (RR) between sexes, tissues, sires and -- perhaps
-- individuals. As Weller pointed out, genetic theory has treated
RR as a single parameter, but the evidence begins to hint that it may well
be a random  variable following a distribution indexed by some
hyper-parameters. Here comes my point.

I  suppose that these "differences" have been assessed by some likelihood
based technique in which RR is a fixed parameter. Then, the null hypothesis
of no differences in RR has been rejected often. It is well known that if
in a Gaussian model you treat a random variable as a fixed parameter, one
tends to reject the null hypothesis perhaps too often.

How strong is the evidence? How credible are the statistical analyses
conducted so far?

The theoretical implications of possible variability (random or not) in
recombination rate are enormous. For example, the degree of resemblance
between relatives depends (at least for some epistatic effects) on
recombination rate. If this varies between sexes, the degree of resemblance
is non -trivially affected by this ( similar to the situation with
sex-linxed loci). If RR varies at random, then the correct calculation of
the covariances between relatives needs knowledge of the distribution of
RR.

Please make sure that these results are credible beyond reasonable doubt.
If these turn to be credible, a major  revamp of quantitative genetic
theory will be in order.

Date: Fri, 22 Oct 1993 13:24:34 +1000
From: Bill Barendse 
Subject: variability in RR

We evaluate recombination rate as a variable and maximize the likelihood
over a range of R compared to a null hypothesis of R = 0.5.  This is for 
the detection of linkage with sexes pooled - the standard lodscore procedure.
We have used a threshold of lod > 3.0 for the first 100 loci and then increased 
the threshold as the number of loci have increased (lod > 5.0 for 200 loci).
For statistically significant sex pooled lods we compare the lods for sexes
pooled compared to maximized lods for sexes separate using a chi-squared
test with one degree of freedom.  However, for each chromosome we divide the
significance threshold by the number of pairwise tests.  Therefore, for the
chromosome 21 data I mentioned earlier, the effective threshold is 0.0045 and
we find chi-squared values of 10 through 22, well over this threshold.  In
addition, the likelihoods for multipoint maps are calculated with R for
sexes pooled and sexes separate.  These likelihoods are compared using
likelihood ratios which are transformed into chi-squared values. 
For ch21 the chisquare (4df) is 28.2, p < 0.001.  In this study the number of
informative meioses varies from 186 to 265.  In the paper the number of
meioses is reported as the number of offspring in informative matings but as
the loci have an average heterozygosity of 0.82 the numbers of offspring are
lower than the numbers of informative meioses.

In addition to these numbers it is clear that several groups can find the 
same effect with loci in the same region of the genome using other populations 
or techniques - Harris finds the same effect in BoLA and its surrounds as I
do.  We have also found that comparisons between bivariate and univariate R
over the same region of the gene map gives the same deviation between sexes 
when different sets of loci are compared although this kind of evidence is not
as strong as evidence from different studies.

Here's a bit of speculation - does the evolutionary lifestyle of the species 
cause differences in recombination rate between species?  Herd beasts where
the selection is more on males, or species with males defending territories
may have less recombination than the females.  Species with females that don't
move about much or that have males that leave their birth area may have males
with more recombination than females.  Does phylogeny matter in this regard? 
Does it fit the facts?

From: BLOOD%UIUCVMD@isumvs.iastate.edu
Date: 24 Oct 1993 11:44:02 CDT

In our experiment, which detected significant differences between bulls
for recombination rate, sperm typing was employed.  The theta obtained
from typing 254 sperm from one bull were compared with the theta
obtained from another bull, for which 176 sperm were typed.  The former
experiment was described in van Eijk et al., Mammalian Genome,
4:113-118, 1993.  Thetas were compared according to the method published
by Cui et al., PNAS 86:9389-9393, 1989.

From: Lyman Crittenden 
Subject: Recombination and Sex
Date: Wed, 27 Oct 93 11:25:11 EDT

This relates to differences in recombination rates due to sex of the
double hetrozygous parent.

The two international reference populations for chicken mapping are held
in Compton, UK and East Lansing, MI, USA.  Both are backcrosses.  The
Compton panel uses the F1 female while the East Lansing panel uses the F1
male.  With limited common markers that are linked, so far we have found no
gross trend for a higher recombination rate in either population.  
The maps also cover about the same number of cM.  Obviously we need more
data.

Harris Lewin said that there is evidence for a difference in birds.  Are
there published references?

Lyman Crittenden  crit@poultry.mph.msu.edu 

Date: Fri, 29 Oct 1993 09:25:23 +0100 (CET)
From: Mike.Grossman@alg.vf.wau.nl
Subject: re: Recombination rates

I'd like to add some interesting references to the discussion on recombination
rates.  Peter Dawson (Genetics, 72:525, 1972) found sex differences for 
recombination in TRIBOLIUM, with XO higher in females than in males for 
linkage group IV.  There are reports (see Dawson) of XO greater in males for 
Linkage group VII, but equal for IV and V.  Clearly it depends on the linkage 
group.  Also in Dawson is a reference to Dunn and Bennett (Genet. Res., 9:211,
1967) who reviewed sex differences in recombination of linked genes in 
animals.  Perhaps that paper will be helpful to the discussion.
	Also, Andy DeWees (Genetics, 81:537, 1975) selected for high and low 
recombination rate in TRIBOLIUM.  Recombination rate increased, as a result of
selection and not drift he says, but there was no downward trend.  It appears 
as if there was additive genetic variance for recombination rate (H^2 = .16).  
He argues that under a polygenic model in which low recomb. rate is dominant to high, average rates will increase as inbreeding increases, because of an 
increase in recessives. He has an interesting discussion in the paper.

Date:         Fri, 12 Nov 93 11:33:56 MEZ
From: Henner Simianer 

Dear genemappers,
the discussion on variability of recombination rates seems
to be more or less finished. Maybe I may add a last observation,
that I have tested the hypothesis of a fixed male recombination
rate between the casein genes in cattle, and this hypothesis
was rejected in virtually all cases (on a very convincing
significance level). So, this hypothesis that the recombination
rate is the same in all sires certainly does not hold. I have,
however, no further information on the sires (e.g. age) yet, so
I cannot analyse the reasons for this variability, but I am
working on getting these informations. Anyway, the discussion
on this topic was very informative and I want to thank all
the people who contributed.

Programs for Linkage Analysis

To:	plant scientists interested in quantitative trait loci mapping
	(Jim Coors, Jeff Harper, Mike Havey, Jim Nienhuis, Tom Osborn,
	Mike Sussman, Bill Tracy, Rick Vierstra, ...)
Re:	working group to examine Lander and related material
From:	Brian Yandell

Several people have approached me with questions or concerns about recent
work on RFLP linkage maps and quantitative trait loci.  This has been
heightened by the recent availability of a computer program to easily
(we hope) conduct certain anaylses.  The basic question:  what does this
stuff do, and is it right for your research needs?

I have set up a preliminary meeting on THU 12 JULY, 2pm, 320 Plant Sciences.
I now have some understanding of the statistical issues involved, but want
to clarify what questions plant scientists really want to address using RFLPs
and related tools.  While I want to share my findings, more importantly I
want to be a resource for your developing research needs in this area.

You may want to examine one or more papers before coming.  Here is a list,
with the main papers (I think?) starred.  (Come cold if you want, though.)

REFERENCES
E: examples of use; P: program package; M: mathematical model.

[E] C. Chang, J. L. Bowman, A. W. de John, E. S. Lander and E. M. Meyerowitz
(1988) Restriction fragment length polymorphism linkage map for Arabidopsis
thaliana.  Proc. Natl. Acad. Sci. USA 85: 6856-6860.
	use MAPMAKER on Arabidopsis to construct RFLP linkage map
	90 markers (>50% within 1.9cM of fragments); 225 F3 pools

[M] J. B. S. Haldane and C. A. B. Smith (1947) A new estimate of the linkage between
the genes for colour-blindness and haemophilia in man.
Ann. Eugenics 14: 10-31.
	probability model groundwork for Lander models
	considers 2 traits in small 3-generation pedigrees
	mathematical but with helpful graphics

[P] Lander Lab (1990) MAPMAKER distribution notes for specific computer systems.
Whitehead Institute for Biomedical Research, Cambridge, MA.
	sketchy specs for MAPMAKER-II and /QTL on various machines
	refers to Lander et al. (1987) and Paterson et al. (1988) for examples

[M] E. S. Lander and D. Botstein (1986) Strategies for studying heterogeneous genetic
traits in humans by using a linkage map of restriction fragment length
polymorphisms.  Proc. Natl. Acad. Sci. USA 83: 7353-7357.
	intro to interval mapping ideas for probability model
	discussion of sample size (careful!)

[M] E. S. Lander and D. Botstein (1989) Mapping Mendelian factors underlying
quantitative traits using RFLP linkage maps.  Genetics 121: 185-199.
	layout of (part of) probability model
	simulation study with 250 B1 progeny, 12 chromosomes x 6 markers; 5 QTLs

[M] E. S. Lander and P. Green (1987) Construction of multilocus genetic linkage maps
in humans.  Proc. Natl. Acad. Sci. USA 84: 2363-2367.
	details of estimation method
	sequential estimation along proposed linkage order

[P] E. S. Lander, P. Green, J. Abrahamson, A. Barlow, M. J. Daly, S. E. Lincoln and
L. Newburg (1987) MAPMAKER: an interactive computer package for constructing
primary genetic linkage maps of experimental and natural populations.
Genomics 1: 174-181.
	nice examples of MAPMAKER capabilities
	shows some MAPMAKER commands and outputs

[E] H-G. Nam, J. Giraudat, B. den Boer, F. Moonan, W. D. B. Loos, B. M. Hauge and
H. M. Goodman (1989) Restriction fragment length polymorphism linkage map of
Arabidopsis thaliana. The Plant Cell 1: 699-705.
	use MAPMAKER on Arabidopsis for RFLP linkage map
	adds 94 markers to 17 from Chang et al.; 118 F2 plants (F3 pools of 100-1000)

[E] A. H. Paterson, J. W. deVerna, B. Lanini and S. D. Tanksley (1990) Fine mapping
of quantitative trait loci using selected overlapping recombinant chromosomes,
in an interspecies cross of tomato.  Genetics 124: 735-742.
	6 genetic stocks; 150 selfers/stock; 237 B1 progeny

[E] A. H. Paterson, E. S. Lander, J. D. Hewitt, S. Peterson, S. E. Lincoln and
S. D. Tanksley (1988) Resolution of quantitative traits into Mendelian factors
by using a complete linkage map of restriction fragment length polymorphisms.
Nature 335: 721-726.
	early example of MAPMAKER use with QTLs on tomatos
	70 markers; 237 B1 progeny

New references added from RFLP colloquium:

Cowen (1988) TAG 75: 857.

Hillel et al. (1990) Genetics 124: 783
	markers for BC breeding

Keim et al (1990) Genetics 126: 739.
Keim et al. (1990) TAG 79: 465.

Lande and Thompson (1990) Genetics 124: 743.
	theoretical background

Luo and Kearsey (1989) Heredity (Lond.) 63: 401.
Luo and Kearsey (1991) Heredity (Lond.) 66: 117.

Paterson et al. (1990) Genetics 124: 735
	aid of substitution mapping

Paterson et al. (1991) Genetics 127: 181.
Soller et al. (1976) TAG 47: 35.
Soller et al. (1978) Biometrics 34: 47.
Weller et al. (1986) Biometics 42: 627.
Weller et al. (1988) Genetics 118: 329.
Date:         Fri, 12 Nov 93 11:33:56 MEZ
From: Henner Simianer 
Subject:      Linkage & QTL programs

I would like to ask a different question about programs for
linkage analysis and mainly QTL detection. I was asked to analyze
cattle data, containing marker genotypes (at about up to 20
loci) and quantitative traits. The information is on several
generations, most likely loops are present, but quantitative
observations are mainly on halfsib groups. There are about
500 genotyped individuals, but probably this number will increase.
As far as I can see, the standard programs available for this
purpose have been designed for human genetic data analyses and certainly
have limitations when applying them with farm animal data.
I would be very interested in any comment on this subject
from people with practical experience. Thanks   Henner Simianer

Marker Assisted Selection

From: sjarvis@peg.pegasus.oz.au
Date: Wed, 20 Jul 1994 18:44:07 +1100
Subject: cost benefit of MAS vs traditional breeding

I was wondering if anyone would mind helping a tree breeder (ex
animal breeder) with some ideas on comparing cost benefits
of marker assisted selection with traditional breeding approaches.
We are helping another organisation to prepare a presentation to
attract industry funding, and I feel out of my depth.

I know that MAS will drastically reduce the generation length (and
that's a big plus for us tree people), but how much increase in
accuracy should one assume for polygenic traits? How do you get
a handle on costs. Has any similar type of analysis been done
in animal breeding?

I don't have access to a scientific academic library holding animal
breeding journals here in Mount Gambier, so any photocopies of
relevant papers would be very welcome.

Susan Jarvis   Southern Tree Breeding Association
               PO Box 1811
               Mt Gambier
               South Australia 5290

phone: 087-230688 (+61 087 230688 international)
fax:   087-230660

RAPD Markers

Date: Fri, 25 Feb 1994 16:06:20 +0100 (CET)
From: Sijne.vanderBeek@alg.vf.wau.nl

In response to the question of Henner Simianer on the use of RAPD loci etc.:

I think a distinction has to be made between:
a) techniques which result in bands that can be assigned to codominant
   loci, like locus specific micro sattelites
b) techniques which result in bands that can be assigned to dominant
   loci, like (hopelfully) RAPD
c) techniques which just result in bands (one dimensional fingerprinting)
   or spots (two dimensional fingerprinting).

For efficient mapping codominant markers are of course preferred. The 
relative efficiency of dominant markers, like RAPD, depends on the situation. 
Dominant markers can be useful if a backcross of inbred lines is used. Let 
the cross be AB * B. If the dominant allele is fixated in line A and the 
recessive allele in line B, then this setup has maximum efficiency for 
linkage mapping. As soon as the dominant allele is fixated in line B the 
efficiency is zero. For RAPDs this is no problem because you just generate 
abundant numbers and select the good ones. In segregating populations the 
situation is worse. The efficiency of dominant markers is then low, 
especially if the dominant allele has a high frequency. The problem is that a 
family is worthless as soon as one parent is homozygous for the dominant 
locus. Some theoretical work on the design of linkage mapping studies has 
been done by Van der Beek et al. Animal Biotechnology 4(2): 163-182(1993). 
Yes this is advertisement. In this study both codominant and dominant markers 
were taken into account.

Microsatellite Markers

From: weller@aipl.arsusda.gov
Subject: microsatellites for identification
Date: Tue, 5 Apr 1994 16:34:20 -0400 (EDT)

Ron, M., Band, M., Wyler, A., and Weller, J. I. (1993)  Unequivocal
determination of sire allele origin for multiallelic microsatellites when
only the sire and progeny are genotyped.  Anim. Genet. 24; 171-176.

Microsatellites should be better than blood groups for paternity
identification because the number of alleles is generally greater.  With
respect to reliability and cost, I also know that Genemark was working on a
kit for paternity identification using microsatellites, and that Harris Lewin
at Urbana tested it.  You may want to contact him.  All the best.

Map Functions and Interference

Date: Tue, 2 Nov 1993 14:37:48 +1000
From: Bill Barendse 
Subject: interference

In a few articles in the mid '80s Morton, MacLean and colleagues examined 
the degree of interference found in recombination fractions.  In essence 
they show that interference is unlikely to be represented by a single 
parameter for all occasions.  However, in all cases that they examined 
interference was found, usually at levels greater than that contained 
in the Kosambi mapping function.

Morton, N.E., MacLean, C.J., and Lew, R.  1985.  Tests of hypotheses on 
recombination fractions.  Genet. Res.  45: 279 - 286.

Morton, N.E., and MacLean, C.J. 1984.  Multilocus recombination frequencies.
Genet. Res.  44: 99 - 108.

Morton, N.E., MacLean, C.J., Lew, R., and Yee, S.  1986.  Multipoint linkage 
analysis.  Am. J. Hum. Genet.  38: 868 - 883.

Interference is the measure of the amount of reduction in double, triple and
higher order recombination events that occur between a pair of arbitrarily
chosen loci.  Since these higher order recombination events occur at a 
frequency equal to the product of the primary recombination fractions they
add little to the distance between loci when there is no interference.
Indeed, to discriminate between complete and no interference requires 
hundreds of meioses.  Differences in interference may be a possible
explanation when the differences between males and females are only one or
two percent but some of the differences are as large as an order of magnitude. 
So I think that if interference plays a role in differences in recombination
fractions between sexes it would be very difficult to demonstrate that it 
did so and we probably wouldn't have found the differences.

Computational Medicine

From: bumble@hermes.chpc.utexas.edu (Leslie Bockoven)
Subject: COMPMED 94 CONFERENCE ANNOUNCEMENT
Date: Tue, 14 Sep 93 16:24:56 CDT

		FIRST WORLD CONGRESS
      ON COMPUTATIONAL MEDICINE, PUBLIC HEALTH AND
                     BIOTECHNOLOGY
                    24-28 April 1994
                   Hyatt Regency Hotel
                     Austin, Texas

1.0 CONFERENCE OVERVIEW:  With increasing frequency, 
computational sciences are being exploited as a means 
with which to investigate biomedical processes at all 
levels of complexity; from molecular to systemic to 
demographic. Computational instruments are now used, 
not only as exploratory tools but also as diagnostic 
and prognostic tools. The appearance of high 
performance computing environments has, to a great 
extent, removed the problem of increasing the 
biological reality of the mathematical models. For the 
first time in the history of the field, practical 
biological reality is finally within the grasp of the 
biomedical modeler. Mathematical complexity is no 
longer as serious an issue as speeds of computation 
are now of the order necessary to allow extremely 
large and complex computational models to be analyzed. 
Large memory machines are now routinely available.  
Additionally, high speed, efficient, highly optimized 
numerical algorithms are under constant development. 
As these algorithms are understood and improved upon, 
many of them are transferred from software 
implementation to an implementation in the hardware 
itself; thereby further enhancing the available 
computational speed of current hardware. The purpose 
of this congress is to bring together a 
transdisciplinary group of researchers in medicine, 
public health, computer science, mathematics, nursing,
veterinary medicine, ecology, allied health, as well 
as numerous other disciplines, for the purposes of 
examining the grand challenge problems of the next 
decades. This will be a definitive meeting in that it 
will be the first World Congress of its type and will 
be held as a follow-up to the very well received 
Workshop On High Performance Computing In The Life 
Sciences and Medicine held by the University of Texas 
System Center For High Performance Computing in 1990.

Young scientists (graduate students, postdocs, etc.)
are encouraged to attend and to 
present their work in this increasingly interesting 
discipline. Funding is being solicited from NSF, NIH, 
DOE, Darpa, EPA, and private foundations, as well as 
other sources to assist in travel support and in the 
offsetting of expenses for those unable to attend 
otherwise. Papers, poster presentations, tutorials, 
focused topic workshops,  birds of a feather groups, 
demonstrations, and other suggestions are also 
solicited.

2.0 CONFERENCE SCOPE AND TOPIC AREAS: The Congress 
has a broad scope. If you are not sure
whether or not your subject fits the Congress 
scope, contact the conference organizers at one 
of the addresses below.

Subject areas include but are not limited to:
*Visualization/Sonification
 --- medical imaging
 --- molecular visualization as a clinical 
     research tool
 --- simulation visualization
 --- microscopy
 --- visualization as applied to problems 
     arising in computational molecular 
     biology and genetics or other non-traditional 
     disciplines
 --- telemedicine
*Computational Molecular Biology and Genetics
 --- computational ramifications of clinical 
     needs in the Human Genome, Plant Genome, 
     and Animal Genome Projects
 --- computational and grand challenge problems in
     molecular biology and genetics
 --- algorithms and methodologies
 --- issues of multiple datatype databases
*Computational Pharmacology, Pharmacodynamics, 
    Drug Design
*Computational Chemistry as Applied to Clinical Issues
*Computational Cell Biology, Physiology, 
    and Metabolism
 --- Single cell metabolic models (red blood cell)
 --- Cancer models
 --- Transport models
 --- Single cell interaction with external factors 
     models (laser, ultrasound, electrical stimulus)
*Computational Physiology and Metabolism
 --- Renal System
 --- Cardiovascular dynamics
 --- Liver function
 --- Pulmonary dynamics
 --- Auditory function, coclear dynamics, hearing
 --- Reproductive modeling: ovarian dynamics, 
     reproductive ecotoxicology, modeling the 
     hormonal cycle 
 --- Metabolic Databases and metabolic models
*Computational Demography, Epidemiology, and 
    Statistics/Biostatistics
 --- Classical demographic, epidemiologic, 
     and biostatistical modeling
 --- Modeling of the role of culture, poverty, 
     and other sociological issues as they 
     impact healthcare 
 --- Morphometrics
*Computational Disease Modeling
 --- AIDS
 --- TB
 --- Influenza
 --- Statistical Population Genetics Of Disease
     Processes
 --- Other
*Computational Biofluids
 --- Blood flow
 --- Sperm dynamics
 --- Modeling of arteriosclerosis and related
     processes
*Computational Dentistry, Orthodontics, and 
    Prosthetics
*Computational Veterinary Medicine 
 --- Computational issues in modeling non-human 
     dynamics such as equine, feline, canine dynamics 
     (physiological/biomechanical)
*Computational Allied Health Sciences
 --- Physical Therapy
 --- Neuromusic Therapy
 --- Respiratory Therapy
*Computational Radiology
 --- Dose modeling
 --- Treatment planning
*Computational Surgery
 --- Simulation of surgical procedures in VR worlds
 --- Surgical simulation as a precursor to surgical 
     intervention
 --- The Visible Human
*Computational Cardiology
*Computational Nursing
*Computational Models In Chiropractice
*Computational Neurobiology and Neurophysiology 
 --- Brain modeling
 --- Single neuron models
 --- Neural nets and clinical applications
 --- Neurophysiological dynamics 
 --- Neurotransmitter modeling
 --- Neurological disorder modeling (Alzheimer's 
     Disease, for example)
 --- The Human Brain Project
*Computational Models of Psychiatric and Psychological
    Processes
*Computational Biomechanics
 --- Bone Modeling
 --- Joint Modeling
*Computational Models of Non-traditional Medicine
 --- Acupuncture
 --- Other
*Computational Issues In Medical Instrumentation
 Design and Simulation
 --- Scanner Design 
 --- Optical Instrumentation
*Ethical issues arising in the use of computational
 technology in medical diagnosis and simulation
*The role of alternate reality methodologies
 and high performance environments in the medical and
 public health disciplines
*Issues in the use of high performance computing 
 environments in the teaching of health science 
 curricula
*The role of high performance environments
 for the handling of large medical datasets (high
 performance storage environments, high performance
 networking, high performance medical records 
 manipulation and management, metadata structures
 and definitions)
*Federal and private support for transdisciplinary 
 research in computational medicine and public health

3.0 CONFERENCE COMMITTEE

*CONFERENCE CHAIR: Matthew Witten, UT System Center 
For High Performance Computing, Austin, Texas
m.witten@chpc.utexas.edu

*CURRENT CONFERENCE DIRECTORATE: 
Regina Monaco, Mt. Sinai Medical Center
Dan Davison, University of Houston  
Chris Johnson, University of Utah 
Lisa Fauci, Tulane University 
Daniel Zelterman, University of Minnesota Minneapolis
James Hyman, Los Alamos National Laboratory
Richard Hart, Tulane University  
Dennis Duke, SCRI-Florida State University  
Sharon Meintz, University of Nevada Los Vegas  
Dean Sittig, Vanderbilt University  
Dick Tsur, UT System CHPC  
Dan Deerfield, Pittsburgh Supercomputing Center 
Istvan Gyori, University of Veszprem (Hungary)
Don Fussell, University of Texas at Austin  
Ken Goodman, University Of Miami School of Medicine  
Martin Hugh-Jones, Louisiana State University 
Stuart Zimmerman, MD Anderson Cancer Research Center  
John Wooley, DOE  
Sylvia Spengler, University of California Berkeley   
Robert Blystone, Trinity University 
Gregory Kramer, Santa Fe Institute
Franco Celada, NYU Medical Center
David Robinson, NIH, NHLBI
Jane Preson, MCC
Peter Petropoulos, Brooks Air Force Base
Marcus Pandy, University of Texas at Austin
George Bekey, University of Southern California
Stephen Koslow, NIH, NIMH
Fred Bookstein, University of Michigan Ann Arbor
Dan Levine, University of Texas at Arlington
Richard Gordon, University of Manitoba (Canada)
Stan Zeitz, Drexel University
Marcia McClure, University of Nevada Las Vegas
Renato Sabbatini, UNICAMP/Brazil (Brazil)
Hiroshi Tanaka, Tokyo Medical and Dental University (Japan)
Shusaku Tsumoto, Tokyo Medical and Dental University (Japan)

Additional conference directorate members are
being added and will be updated on the anonymous
ftp list as they agree.

4.0 CONTACTING THE CONFERENCE COMMITTEE: To contact
the congress organizers for any reason use any of the 
following pathways:

ELECTRONIC MAIL - compmed94@chpc.utexas.edu

FAX (USA)       - (512) 471-2445

PHONE (USA)     - (512) 471-2472

GOPHER: log into the University of Texas System-CHPC
select the Computational Medicine and Allied Health
menu choice

ANONYMOUS FTP: ftp.chpc.utexas.edu
               cd /pub/compmed94
POSTAL:
            Compmed 1994
	    University of Texas System CHPC
	    Balcones Research Center
	    10100 Burnet Road, CMS 1.154
	    Austin, Texas 78758-4497 

5.0 SUBMISSION PROCEDURES: Authors must submit 5 
copies of a single-page 50-100 word abstract clearly 
discussing the topic of their presentation. In 
addition, authors must clearly state their choice of 
poster, contributed paper, tutorial, exhibit, focused
workshop or birds of a feather group along with a 
discussion of their presentation. Abstracts will be 
published as part of the preliminary conference 
material. To notify the congress organizing committee 
that you would like to participate and to be put on 
the congress mailing list, please fill out and return 
the form that follows this announcement.  You may use 
any of the contact methods above. If you wish to 
organize a contributed paper session, tutorial 
session, focused workshop, or birds of a feather 
group, please contact the conference director at 
mwitten@chpc.utexas.edu . The abstract may be submitted
electronically to  compmed94@chpc.utexas.edu  or
by mail or fax. There is no official format.


6.0 CONFERENCE DEADLINES AND FEES: The following deadlines 
should be noted:

     1 November  1993 - Notification of intent to organize
                        a special session 

     15 December 1993 - Abstracts for talks/posters/
                        workshops/birds of a feather 
                        sessions/demonstrations

     15 January  1994 - Notification of acceptance of 
                        abstract

     15 February 1994 - Application for financial aid

     1 April     1994 - Registration deadline
	                (includes payment of all fees)

Fees include lunches for three days, all conference
registration materials, the reception, and the sit
down banquet: 

	$400.00 Corporate
	$250.00 Academic
	$150.00 Student

Students are required to submit verification of student
status. The verification of academic status form appears
appended to the registration form in this announcement.

Because financial aid may be available for minority
students, faculty, and for individuals from declared
minority institutions, you may indicate that you are
requesting financial aid as a minority individual.
Additionally, we anticipate some support for women to
attend. Application for financial aid is also appended
to the attached form.


7.0 CONFERENCE PRELIMINARY DETAILS AND ENVIRONMENT

LOCATION: Hyatt Regency Hotel, Austin, Texas, USA
DATES:    24-28 April 1994

The 1st World Congress On Computational Medicine, 
Public Health, and Biotechnology will be held at the 
Hyatt Regency Hotel, Austin, Texas located in 
downtown Austin on the shores of Town Lake, also 
known as the Colorado River. The Hyatt Regency has 
rooms available for the conference participants at 
a special rate of $79.00/night for single or double 
occupancy, with a hotel tax of 13%. The Hyatt accepts 
American Express, Diner's Club, Visa, MasterCard, 
Carte Blanche, and Discover credit cards. This room 
rate will be in effect until 9 April 1994 or until 
the block of rooms is full. We recommend that you make
your reservations as soon as possible. You may make 
your reservations by calling (512) 477-1234 or by 
returning the enclosed reservation form. Be certain 
to mention that you are attending the First World 
Congress On Computational Medicine, Public Health, 
and Biotechnology if you make your reservations by 
telephone. 

The hotel is approximately, five miles (15 minutes 
>from Robert Mueller Airport). The Hyatt offers 
courtesy limousine service to and from the airport 
between the hours of 6:00am and 11:00pm. You may call 
them from the airport when you arrive. If you choose 
to use a taxi, expect to pay approximately $8.00. 
Automobiles may be rented, at the airport, from most 
of the major car rental agencies. However, because of 
the downtown location of the Congress and access to 
taxis and to bus service, we do not recommend that you 
rent an auto unless you are planning to drive 
outside of the city. 

Should you be unable to find an available room at the 
Hyatt Regency, we have scheduled an "overflow" hotel. 
Please contact the conference coordinator for more 
information.

Austin, the state capital, is renowned for its natural 
hill-country beauty and an active cultural scene. 
Several hiking and jogging trails are within walking 
distance of the hotel, as well as opportunities for a 
variety of aquatic sports. From the Hyatt, you can 
"Catch a Dillo" downtown, taking a ride on our 
delightful inner-city, rubber-wheeled trolley system. 
In Austin's historic downtown area, you can take a 
free guided tour through the State Capitol Building, 
constructed in 1888. Or, you can visit the Governor's 
Mansion, recognized as one of the finest examples of 
19th Century Greek Revival architecture and housing 
every Texas governor since 1856. Downtown you will 
find the Old Bakery and Emporium, built by Swedish 
immigrant Charles Lundberg in 1876 and the Sixth 
Street/Old Pecan Street Historical District - a 
seven-block renovation of Victorian and native stone 
buildings, now a National Registered Historic District 
containing more than 60 restaurants, clubs, and 
shops to enjoy. The Laguna Gloria Art Museum, the
Archer M. Huntington Art Gallery, the LBJ Library and
Museum, the Neill-Cochran Museum House, and the Texas
Memorial Museum are among Austin's finest museums.
The Umlauf Sculpture Garden, has become a major 
artistic attraction. Charles Umlauf's sculptured works 
are placed in a variety of elegant settings under a 
canopy of trees. The Zilker Gardens contains many 
botanical highlights such as the Rose Garden, Oriental 
Garden, Garden of the Blind, Water Garden and more. 
Unique to Austin is a large population of Mexican 
free-tailed bats which resides beneath the Congress 
Avenue Bridge. During the month of April, the Highland 
Lakes Bluebonnet Trail celebrates spring's wildflowers 
(a major attraction) as this self-guided tour winds 
through the surrounding region of Austin and nearby 
towns (you will need to rent a car for this one).

Austin offers a number of indoor shopping malls in 
every part of the city; The Arboretum, Barton Creek 
Square, Dobie Mall, and Highland Mall, to name a few. 
Capital Metro, Austin's mass transit system, offers 
low cost transportation throughout Austin. Specialty 
shops, offering a wide variety of handmade crafts and 
merchandise crafted by native Texans, are scattered 
throughout the city and surrounding areas.

Dining out in Austin, you will have choices of 
American, Chinese, Authentic Mexican, Tex-Mex, 
Italian, Japanese, or nearly any other type of cuisine 
you might wish to experience, with price ranges that 
will suit anyone's budget. Live bands perform in 
various nightclubs around the city and at night spots 
along Sixth Street, offering a range of jazz, blues, 
country/Western, reggae, swing, and rock music. 

Day temperatures will be in the 80-90(degrees F) range 
and fairly humid. Evening temperatures have been known 
to drop down into the 50's (degrees F). Cold weather
is not expected so be sure to bring lightweight 
clothing with you. Congress exhibitor and vendor 
presentations are also being planned.

8.0 CONFERENCE ENDORSEMENTS AND SPONSORSHIPS: 
Numerous potential academic sponsors have been
contacted. Currently negotiations are underway
for sponsorship with SIAM, AMS, MAA, IEEE, FASEB, and
IMACS. Additionally AMA and ANA continuing medical
education support is being sought. Information
will be updated regularly on the anonymous ftp
site for the conference (see above). Currently,
funding has been generously supplied by the following
agencies:

University of Texas System - CHPC
U.S. Department of Energy

================== REGISTRATION FORM ===============

(Please list your name below as it will appear on badge.)
First Name :

Middle Initial (if available):

Family Name:

Your Professional Title:

       [ ]Dr.
       [ ]Professor
       [ ]Mr.
       [ ]Mrs.
       [ ]Ms.
       [ ]Other:__________________

Office Phone (desk):

Home/Evening Phone (for emergency contact):

Fax:

Electronic Mail (Bitnet):

Electronic Mail (Internet):

Postal Address:
       Institution or Center:
       Building Code:
       Mail Stop:
       Street Address1:
       Street Address2:
       City:
       State:
       Zip or Country Code:
       Country:

Please list your three major interest areas:

       Interest1:
       Interest2:
       Interest3:

Registration fee:                       $____________
Late fee $50 (if after April 1, 1994)   $____________

**IF UT	AUSTIN, PLEASE PROVIDE YOUR:
UNIVERSITY ACCT. #:     ______________________
UNIVERSITY ACCT. TITLE: ______________________
NAME OF ACCT. SIGNER:   ______________________
=====================================================

                      VERIFICATION OF STUDENT STATUS

Name:

Mailing Address:


University at which you are a student:

What level student(year):

Your student id number:

Name of your graduate or postdoctoral advisor:

Telephone number for your advisor:

By filling in this section, I agree that I am electronically
signing my signature to the statement that I am currently
a student at the above university.


=======================================================
		      REQUEST FOR FINANCIAL AID	

Name:


Mailing Address:


I request financial assistance under one or more
of the following categories:

[ ] Student (You must fill out the Verification of Student
	     Status Section in order to be considered for
	     financial aid under this category)

[ ] Academic


[ ] Minority
	
	[ ] Female
	[ ] Black
	[ ] Hispanic
	[ ] Native American Indian
	[ ] Other

This form is not meant to invade your personal privacy in
any fashion. However, some of the grant funds are targeted
at specific ethnic/minority groups and need to be expended
appropriately. None of these forms will be in any way 
released to the public. And, after the congress, all of
the financial aid forms will be destroyed. No records will
be kept of ethnic or racial backgrounds.

If you have any questions concerning financial aid support,
please contact Matthew Witten at the above addresses.

Last modified: Wed Sep 6 11:26:07 1995 by Brian Yandell
yandell@stat.wisc.edu