From jillian.maddox alumni.unimelb.edu.au Wed Mar 28 19:28:50 2012
From: Jill Maddox <jillian.maddoxalumni.unimelb.edu.au>
To: Multiple Recipients of <SheepModelsanimalgenome.org>
Subject: sheep HD SNP array and MHC typing
Date: Wed, 28 Mar 2012 19:28:50 -0500
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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