linking animal models to human diseases supported by nih p41 hg002659 and u54 hg002659 the...
TRANSCRIPT
Linking Animal Models to Human Diseases
Supported by NIH P41 HG002659 and U54 HG002659
the University of Oregon, Eugene, OR
http://zfin.org
1. Goals• Annotate zebrafish phenotypes• Identify human disease models
2. Example - holoprosencephaly
3. Progress
Animal models
Mutant Gene
Mutant or missing Protein
Mutant Phenotype
Zebrafish disease models:
Humans Animal models
Mutant Gene
Mutant or missing Protein
Mutant Phenotype
(disease)
Mutant Gene
Mutant or missing Protein
Mutant Phenotype
(disease model)
Zebrafish disease models:
Humans Animal models
Mutant Gene
Mutant or missing Protein
Mutant Phenotype
(disease)
Mutant Gene
Mutant or missing Protein
Mutant Phenotype
(disease model)
Zebrafish disease models:
Humans Animal models
Mutant Gene
Mutant or missing Protein
Mutant Phenotype
(disease)
Mutant Gene
Mutant or missing Protein
Mutant Phenotype
(disease model)
Zebrafish disease models:
1. Goals• Annotate zebrafish phenotypes• Identify human disease models
2. Example - holoprosencephaly
3. Progress
SHH-/+ SHH-/-
shh-/+ shh-/-
Phenotypic character = entity + attribute + value
Phenotypic character = entity + attribute + value
PC1 = eye + placement + mislocalized
Phenotypic character = entity + attribute + value
PC1 = eye + placement + mislocalizedPC2 = midface + structure + hypoplastic
Phenotypic character = entity + attribute + value
PC1 = eye + placement + mislocalizedPC2 = midface + structure + hypoplasticPC3 = kidney + size + hypertrophied
Phenotypic character = entity + attribute + value
PC1 = eye + placement + mislocalizedPC2 = midface + structure + hypoplasticPC3 = kidney + size + hypertrophied
PATO: attribute = placement value = mislocalized
attribute = structure value = hypoplastic
attribute = size value = hypertrophied
ZFIN: entity = eye
entity = midface
entity = kidney
+
Anatomical ontology
Cell & tissue ontology
Developmental ontology
Gene ontology
biological process
molecular function
cellular component
+ PATO
Phenotypiccharacter = entity + attribute + value
Phenotypic character = entity + attribute + value
PC1 = eye + placement + mislocalizedPC2 = midface + structure + hypoplasticPC3 = kidney + size + hypertrophied
Syndrome(or disease) = PC1 + PC2 + PC3
= holoprosencephaly
Human holo-prosencephaly
Zebrafishshh
Zebrafishoep
Human gene:SHH;OMIM:600725 Zebrafish gene:shh Zebrafish gene:oep Ref: OMIM:142945 Ref: ZDB-GENE-980526-166 Ref: ZDB-GENE-990415-198 Entity:prosencephalon development Attribute:process Value:arrested
Entity:prosencephalon development Attribute:process Value:reduced
Entity:prosencephalon development Attribute:process Value:arrested
Entity:brain Attribute:size Value:small
Entity:brain Attribute:size Value:small
Entity:brain Attribute:size Value:small
Entity:brain ventricle Attribute:number Value:single
Entity:brain ventricle Attribute:number Value:single
Entity:midface Attribute:structure Value:hypoplastic
Entity:midface Attribute:structure Value:hypoplastic
Entity:midface Attribute:structure Value:hypoplastic
Entity:eye Attribute:morphology Value:abnormal
Entity:eye Attribute:morphology Value:abnormal
Entity:eye Attribute:morphology Value:abnormal
Entity:eye Attribute:number Value:single
Entity:eye Attribute:number Value:single
Entity:eye Attribute:placement Value:mislocalized
Entity:eye Attribute:placement Value:mislocalized
Entity:eye Attribute:placement Value:mislocalized
Entity:nose Attribute:morphology Value:abnormal
Entity:nose Attribute:morphology Value:abnormal
Entity:nostril Attribute:number Value:single
Entity:nostril Attribute:number Value:single
Entity:kidney Attribute:rel_size Value:hypertrophied
Entity:kidney Attribute:rel_size Value:hypertrophied
Entity:kidney Attribute:rel_size Value:hypertrophied
1. Goals• Annotate zebrafish phenotypes• Identify human disease models
2. Example - holoprosencephaly
3. Progress
ZFINmutantgenes
OMIMgenes
ZFINmutantgenes
OMIMgenes
ZFINmutantgenes
FlyBasemutantgenes
Data type Total
Total ZFIN genes 20,385
Genes with assigned human orthologs 2,884
Genes with OMIM links 2,174
Total ZFIN mutants 3,188
ZFIN mutants with OMIM links
Corresponding human genes
Drosophila homologs of these 271
720
271
187
PATO development:
1. Test curation of zebrafish publications
2. Initial curation of phenotypes
• 200 zebrafish mutations(Tübingen, MIT)
• Morpholino phenotypes (Univ. of Minnesota)
• 400 Medaka mutations (Kyoto)
3. CToL - taxonomy & phylogenies
4. OBO-discuss email list for discussions
Melissa Haendel -anatomy ontology
Doug Howe - GO
Erik Segerdell - PATO
Sierra Taylor - database schema
Supported by NIH P41 HG002659 and U54 HG002659University of Oregon, Eugene, Oregon
http://zfin.org