Characterisation of the molecular defects in the rge, rdd and beg chickens and the search for human disease equivalents.

Lead Research Organisation: University of Leeds
Department Name: Leeds Institute of Molecular Medicine

Abstract

We are studying three strains of blind chickens each with a different inherited eye disease. The chicken is a useful animal model because their eyes are a comparable size to humans.
Using a genetic approach we will find the defective genes which cause blindness in these birds. The corresponding human diseases will also be found by searching the equivalent human gene for defects in DNA samples from patients with various different inherited eye diseases.
This work will increase our understanding of the way the eye works normally, and of ways in which it can go wrong. The identification of the corresponding human condition will allow the early detection of carriers before vision loss has occurred, which will improve the chances for therapy. Where that is not possible, patients and their relatives will benefit from knowing whether they carry the disease, as they will gain a clearer picture of their likely outcome. The availability of chickens with diseases directly equivalent to human eye disease will also help in the search for better treatments.

Technical Summary

This project aims to locate the mutations underlying three chicken models of inherited retinal disease, identify the analogous human phenotypes and characterise the proteins involved. In one chicken line the locus will be identified by whole genome linkage screening, then in this, and a second line, a positional candidate approach will be used to identify the genes. The small chicken genome, high density of recombination, large ?family? size and remarkable conservation of synteny with the human genome make these achievable goals. In the third line, where we have found the gene and mutation, I will look for retinal dystrophy-causing mutations in the human orthologue, characterise the biochemical/cellular consequences of the mutation and determine whether mutations in this gene also contribute to embryonic death. Once identified, the defective proteins in the other lines will also be studied further as appropriate. This work facilitates the use of these chickens to assess therapies.

Publications

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Ali M (2009) Null mutations in LTBP2 cause primary congenital glaucoma. in American journal of human genetics

 
Description Abertay University, Dundee 
Organisation Abertay University
Country United Kingdom 
Sector Academic/University 
PI Contribution We have shared ideas and resources.
Collaborator Contribution We have co-authored two publications together.
Impact We have co-authored two publications 21862650 and 21887213.
 
Description Cardiff University 
Organisation Cardiff University
Department School of Optometry and Vision Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution We have provided significant intellectual input into the collaborator's research.
Collaborator Contribution We have co-authored 3 publications.
Impact 3 publications to date. PubMed ID, 17936639, 19258040 and 21051696.
Start Year 2007
 
Description Roslin Institute 
Organisation University of Edinburgh
Department The Roslin Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution We have provided significant intellectual input into the collaborator's research.
Collaborator Contribution We have co-authored 6 publications to date.
Impact We have co-authored 6 publications to date. PubMed ID, 17936639, 19258040, 20069063, 21051696, 21862650 and 21887213.
 
Description Northern Lights 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact The reporter prepared an article, we edited this and authorised the final version for release. This article was subsequently distributed to various news media eg. Science Daily News, Physorg.com, Medicalnewstoday.com and Traveller Times Magazine.

None known.
Year(s) Of Engagement Activity 2009