Archived Post

From imke.tammensydney.edu.au  Thu Mar 29 18:45:47 2012
From: Imke Tammen <imke.tammensydney.edu.au>
Subject: RE: sheep HD SNP array and MHC typing
To: Multiple Recipients of <SheepModelsanimalgenome.org>
Date: Thu, 29 Mar 2012 18:45:47 -0500

Will be at Isag and think a discussion would be good - agree that whole genome
sequencing needs to be considered as an alternative....

-----Original Message-----
.From: Hickford, Jonathan [mailto:Jonathan.Hickfordlincoln.ac.nz]
.Sent: Friday, 30 March 2012 8:32 AM
.To: Multiple Recipients of <SheepModelsanimalgenome.org>
.Subject: RE: sheep HD SNP array and MHC typing


Hi Jill

Like you can't make it to ISAG for a discussion.

I do wonder how
difficult it might be to develop an array-based typing system that will be of
value when we actually know so very little about sequence variation,
especially outside of the common western World (or European) breeds.  I
suspect we might only be able to "find what we are looking for" and in the
context of Class I especially, that might be very little! This stated, if we
could get a system of any kind working for MHC typing, I could see its
utility
in analysing disease associations.  So, yes I am having a "quid each way".
I am also suspicious that by the time we could iron out a sensible
array-based
typing system, an alternative sequencing option may actually become
available.
The rate of change is such that a whole-genome sequence on any given sheep
might only be US$200 within the decade.  How we will handle all those data,
especially if we have 40 columns of phenotypic data off say 5000 flock ewes
is
beyond me!

Not against a discussion though!


Jon


Jon Hickford
Associate-Professor

Faculty of Agriculture and Life Sciences
Department of
Agricultural Sciences
JBB020
P O Box 84
Lincoln University 7647
Christchurch, New Zealand

p +64 3 325 3838 extn: 8186 | m +64 27 280 1285 |
f +64 3 325 3851
e Jon.Hickfordlincoln.ac.nz | w www.lincoln.ac.nz
Lincoln University, Te Whare Wanaka o Aoraki
New Zealand's Specialist Land
Based University







-----Original Message-----
.From: Jill
Maddox [mailto:jillian.maddoxalumni.unimelb.edu.au]
.Sent: Thursday, 29
March 2012 1:29 p.m.
.To: Multiple Recipients of <SheepModelsanimalgenome.org>
.Subject: sheep HD SNP array
and MHC typing

[ sheepmodels Discussion Mailing List - Mail distributed to

]
Hi Keith and others

Given that the HD SNP array will be able to hold lots
of functional SNPs I
think it is worth trying to come up with a typing
system, but I agree that
we may not know enough especially for class I for it
to be comprehensive.
We can at least aim for it to include all currently
known alleles. Given
that there are lots of segmental exchanges that
contribute to allelic
diversity, it may be a situation whereby if we make the
set of
discriminating SNPs that go on the HD array as comprehensive as
possible
(assuming assay design permits this) that we may end up sorting out
many
haplotypes and MHC types after the array has been used for a bit rather
than beforehand. The ISGC has whole genome sequence information from at
least
80 animals and there are lots of groups that have MHC information
that hasn't
yet made it into GenBank and it would be good if these groups
could also
contribute their sequences to the MHC SNP allele/haplotype
resolving process
too. In terms of which MHC SNPs to include on the chip
they will probably
have to be restricted to those that cause amino acid
changes or have other
functional properties such as affecting expression
levels, premature stop
codons etc. Given the sheep MHC is extremely complex
we will probably need to
set up a working group to handle making
recommendations re which SNPs to
include on the chip. If this was to happen
we would be looking for volunteers
to belong to the working group - please
let me know if you would be
interested in belonging to such a group? Yes, I
think it would be good to
have a discussion at ISAG about this.
Unfortunately I'm unlikely to be able
to attend (funding constraints).

Best wishes from


Jill
At 07:13 PM
28/03/2012, you wrote:
>Hi Jill,
>This is a really interesting point; can a
SNP chip be used to
>accurately type the MHC region of sheep or cattle given
what we
>already know about the exceptional diversity at individual class II
>loci both in terms of allelic and structural diversity  and the
>limited
information we have regarding allelic and haplotype
>diversity within the
class I region.  Obviously we can cover every
>informative SNP within every
allele of every gene identified so far
>but will that tell us anything about
the combinations of SNP's that
>make up each allele within each gene within
the two haplotypes of a
>heterozygous animals.  I don't know enough about
high density SNP
>chip design to answer this but I suppose it depend on what
you need
>to know about the MHC in you study population.  The sequence based
>approaches we are currently using  at least for class II  are time
>consuming and relatively expensive but the data are good. It would
>be
really good to have a discussion on this possibly at the ISAG
>meeting in
July. I am trying to put together the Comparative MHC
>workshop which may be
a good place for this discussion.
>Regards
>Keith
>Dr Keith
Ballingall
>Moredun Research Institute
>Pentlands Science Park
>Bush Loan,
Penicuik
>Midlothian, EH26 0PZ
>Scotland, UK.
>Tel + 44 (0)131 445 5111
>e-mail keith.ballingallmoredun.ac.uk
>-----Original Message-----
>From: Jill Maddox [mailto:jillian.maddoxalumni.unimelb.edu.au]
>Sent: 28
March 2012 00:09
>To: j.pembertoned.ac.uk; j.slatesheffield.ac.uk;
>JGreeffagric.wa.gov.au; jhcalvoaragon.es; Yu.Jiangcsiro.au;
>jillmrubens.its.unimelb.edu.au; jjarrsunileon.es;
>jmm1ualberta.ca;
John.Daniasdownstate.edu;
>john.mcewanagresearch.co.nz;
juha.kantanenmtt.fi;
>julius.vanderwerfune.edu.au; K.Marshallcgiar.org;
Keith
>Ballingall; kgietzenillumina.com; lherrmanvetmed.wsu.edu;
>Yutao.Licsiro.au; Lutz.Bungersac.ac.uk; M.Garcia-Podestaiaea.org;
>magali.san-cristobaltoulouse.inra.fr; martykardosgmail.com;
>massoud.malekiaea.org; matthew.peter.kentumb.no;
>Sean.Mcwilliamcsiro.au;
mike.heatonars.usda.gov;
>mohammadvetsci.usyd.edu.au; msalyayahoo.com;
>msanderyillumina.com; neelamgnbagrgmail.com;
>neil.gemmellotago.ac.nz;
ocobanoglunku.edu.tr;
>Ottmar.Distltiho-hannover.de;
paolo.ajmoneunicatt.it;
>PAScheetmdanderson.org; Paul.Boettcherfao.org;
>Paul.Goodingagrf.org.au; pillaunimol.it; pradeepaspdn.ac.lk;
>raadsmacamden.usyd.edu.au; rgodfreuvi.edu;
>riccardo.negriniunicatt.it;
richard.talbotroslin.ed.ac.uk;
>Rudiger.Brauningagresearch.co.nz;
samuelcenargen.embrapa.br;
>Shannon.Clarkeagresearch.co.nz;
simon.boitardtoulouse.inra.fr;
>sqanbargwdg.de;
stefan.hiendlederadelaide.edu.au;
>stephen.bishopbbsrc.ac.uk;
s.moore3uq.edu.au;
>swhitevetmed.wsu.edu; Ross.Tellamcsiro.au;
>Thomas.Farauttoulouse.inra.fr; tizianasechigmail.com;
>tlonghurstmla.com.au; vs.guptancl.res.in; wangjgenomics.org.cn;
>kworleyBCM.EDU; wwangmail.kiz.ac.cn; xuxungenomics.org.cn;
>zhuiastate.edu; hans.daetwylerdpi.vic.gov.au; lmatukumallinifa.usda.gov
>Subject: Re: Minutes from Sheep Genomics Consortium Call #99
>Hi All
>
>Re the discussion of functional SNPs on the proposed sheep SNP HD
>chip I
think we need to discuss whether we can put sufficient MHC
>SNPs on the chip
to enable accurate MHC typing of sheep.
>I think it would be really useful
for sheep groups conducting
>immunology research to be able to have an
accurate way of doing MHC typing.
>However given the diversity of the MHC
region in sheep this might
>mean devoting a couple of hundred of the
functional SNPs to the MHC
>region and would require development of a SNP
based system for such typing.
>What do others think about one of the uses
of the HD chip being to
>do MHC typing?
>Regards
>Jill
>At 03:47
PM 27/03/2012, James.Kijascsiro.au wrote:
> >2. Parameters for an HD Chip
>
>Chip demand: community wide demand now stands at approximately 15,000
>
>samples in an initial commitment, with at least another 10,000 to
> >follow
after 18 months. Concerning the relative merit of an HD array
> >(800 K  1M
SNP) versus application of emerging genotyping by
> >sequencing
> >(GBS)
approaches, John put the view from AgResearch experimentation
> >that at
present HD arrays are more cost competitive. This may not be
> >the case
where lower density SNP genotyping applications are required.
> >Group
discussed design criteria. This can be summarized as:
> >- functional
content: inclusion of 100K SNP from classes such as
> >non-synonymous SNP,
mis-sense, loss of function, intronic and SNP
> >within promoters etc that
have an inferred functional impact.
> >- spacing: remains essential
> >- LD
structure: tag SNP that efficiently capture haplotypes
> >- rare SNP:
inclusion of SNP that have low MAF to tag rare haplotypes
> >in key breeds.
Assisting in genomic selection.
> >- back compatibility: include all 50K SNP
from existing SNP50 beadchip
>
>***************************************************************
>Jill
Maddox
>16 Park Square
>Port Melbourne, 3207
>Australia
>phone: 03 9646
0428
>E-mail: jillian.maddoxalumni.unimelb.edu.au
>
>***************************************************************
***************************************************************

Jill Maddox
16 Park Square Port Melbourne, 3207 Australia phone: 03 9646
0428 E-mail:
jillian.maddoxalumni.unimelb.edu.au
***************************************************************
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NRSP8 National Animal Genome Research Program - Supported by USDA/NIFA
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