Projects

Comparative MHC Studies in the Dog

Background and Aims

DLA Workshop Protocol

August 2004 Update

April 2005 Update

Background and Aims

The dog is a highly appropriate species to use in studies to investigate how MHC diversity relates to variation in biological function and consequential disease. Clinical conditions in the dog are well recognised and carefully documented in veterinary medicine. Many canine conditions have an immune basis and represent canine homologues of human diseases e.g. diabetes mellitus, anal furunculosis, autoimmune thyroid disease and exocrine pancreatic insufficiency. A greater appreciation of the role of MHC in disease aetiology is likely to benefit both canine health and human medical research.

The dog is unusual in that many hundreds of breeds have arisen through the selective breeding programmes of man for particular traits and the dog is now a model species where phenotype variation is maximised within the confines of the minimal genomic variation of a single species. Dog breeds are in many ways analogous to highly inbred human populations. We already know that some dog breeds have limited MHC allelic diversity and the relationship between breeds, their origins and the increased risk of certain diseases in some breeds may relate to MHC.

A considerable number of DLA class I and II alleles have already been identified and officially named by the International DLA Nomenclature Committee.

Many international initiatives in canine genetics are currently in place and the dog genome has now been sequenced. We now propose an International Workshop collaboration to characterise canine MHC diversity and its relationship with disease susceptibility. This will lead to major advances in our knowledge of canine breed evolution and the field of canine immunogenetics.

Aims:
- To establish the range of DLA class II (DRBI, DQA, DQB) diversity and their distribution in dog breeds
- To identify DLA class II haplotypes by segregation in families
- To examine DLA class II associations with disease susceptibility

DLA Workshop Protocol

The component will be centrally organised from The Centre for Integrated Genomic Medical Research, Manchester, UK. The Organising Committee comprises:

Lorna Kennedy, Bill Ollier, Annette Barnes, Wendy Thomson, Andrea Short, Steven Quarmby and Jason Brown.

The study co-ordinator will be:

Dr Lorna Kennedy
The Centre for Integrated Genomic Medical Research
University of Manchester
Stopford Building
Oxford Road
Manchester, M13 9PT
UK

Tel: +44 (0) 161 275 7316
Fax: +44 (0) 161 275 1617
E-mail: Lorna.Kennedy@man.ac.uk

August 2004 Update

There is already an international flavour to the canine component of the workshop, with laboratories from the UK, Alaska, Germany, Spain and Australia having signed up.
However, there is still time for you to register for participation in the canine DLA diversity component of the 14th International Histocompatibility Workshop.
We would like to match up veterinary laboratories with access to dog samples with HLA laboratories experienced in sequence based typing (SBT). So if you can supply dog samples and not SBT experience or vice versa, please contact Lorna.Kennedy@man.ac.uk and we will find you a suitable partner.

The aims of this component are:

To establish the range of DLA class II (DRBI, DQA, DQB) diversity and their distribution in dog breeds

To identify DLA class II haplotypes by segregation in families

To examine DLA class II associations with disease susceptibility (Diabetes Mellitus, Hypothyroid disease, Exocrine Pancreatic Insufficiency, Anal Furunculosis, Systemic lupus erythematosus)

Already we have samples collected from 400 Diabetic dogs, 50 Hypothyroid dogs, 100 dogs with anal furunculosis, 200 Dobermans and 400 Alaskan Huskies.

We will be mailing detailed protocols in October 2004, together with test DNA samples. Data for the test DNAs should be submitted with the data for each subcomponent, and will be used for quality control purposes.
The deadline for electronic submission of final data is 31st July 2005.

We are negotiating with a software company, and hope to be able to supply a dedicated analysis package to each participating centre. This will include up-to-date allele libraries for DLA-DRB1, DQA1 and DQB1 with 67, 18 and 54 “official” alleles respectively. See http://www.ebi.ac.uk/ipd/mhc/dla/index.html for further information about official DLA alleles, and the activities of the ISAG DLA nomenclature committee. The libraries will also include “unofficial” alleles, making the totals 112 DRB1, 21 DQA1 and 73 DQB1. As new alleles are identified during the workshop, these will be added to the allele libraries and regular updates provided.

We have established an International advisory panel, including Urs Giger (Pennsylvania USA), Elaine Ostrander (Seattle, USA), Stephen O’Brien (Washington, USA), Francis Galibert (Rennes, France), Jennifer Seddon (Australia), Matthew Binns (UK), Niels Pederson (UC Davis, USA) John Wagner (Philadelphia, USA) and Jeff Sampson (The Kennel Club, UK).

A website for the canine workshop component will be online before long: look for a link from the 14th IHW website.

At the workshop meeting in Melbourne we anticipate: redistributing all submitted data, presenting an analysis of the results, including haplotypes and disease associations identified, nomenclature updates and lists of new alleles confirmed or identified during the workshop.
We also hope to persuade the organising committee of the 14th IHW to include a comparative MHC plenary session.

The component will be co-ordinated centrally from The Centre for Integrated Genomic Medical Research, Manchester, UK. The Organising Committee comprises:

Lorna Kennedy, Bill Ollier, Annette Barnes, Andrea Short, Steven Quarmby and Jason Brown.

April 2005 Update

The aims of this component are:

To establish the range of DLA class II (DRBI, DQA, DQB) diversity and their distribution in dog breeds
To identify DLA class II haplotypes by segregation in families
To examine DLA class II associations with disease susceptibility (Diabetes Mellitus, Hypothyroid disease, Exocrine Pancreatic Insufficiency, Anal Furunculosis, Systemic lupus erythematosus)

We have ten laboratories signed up so far, but there is still time for you to register for participation in the canine DLA diversity component of the 14 th International Histocompatibility Workshop.

If you can supply dog samples and not SBT experience or vice versa, please contact Lorna.Kennedy@manchester.ac.uk and we will find you a suitable partner.

Previously we reported that we have samples collected from 400 Diabetic dogs, 50 Hypothyroid dogs, 100 dogs with anal furunculosis, 200 Dobermans and 400 Alaskan Huskies. We now have offers of several multi generation families, which will considerably enhance this study.

Detailed protocols were emailed in January 2005, and test DNA samples will be sent shortly. Data for the test DNAs should be submitted with the data for each subcomponent, and will be used for quality control purposes.

The preferred deadline for electronic submission of final data is 31 st July 2005.

Applied Biosystems have agreed to provide copies of the SeqScape program for participants of this component to analyse their data. This is a major contribution, and we are very grateful to Applied Biosystems for this sponsorship.

We are also trying to get other sponsorship, as a laboratory in Eastern Europe has many interesting samples, but no funding. If anyone is interested in genotyping these samples, please contact Lorna.Kennedy@manchester.ac.uk.

At the workshop meeting in Melbourne we anticipate: redistributing all submitted data, presenting an analysis of the results, including haplotypes and disease associations identified, nomenclature updates and lists of new alleles confirmed or identified during the workshop.

The component is being co-ordinated from The Centre for Integrated Genomic Medical Research, Manchester, UK. The Organising Committee comprises: Lorna Kennedy, Bill Ollier, Annette Barnes, Andrea Short, Steven Quarmby and Jason Brown.

For further information contact:
Dr Lorna Kennedy,

CIGMR, University of Manchester,
Stopford Building, Oxford Road,
Manchester, M13 9PT, UK
Tel: +44 (0) 161 275 7316 Fax: +44 (0) 161 275 1617
E-mail: Lorna.Kennedy@man.ac.uk

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