1. Linking Animal Models to Human Diseases Supported by NIH P41 HG002659 and U54 HG004028 the University of Oregon, Eugene, OR

2. ZFIN: Melissa Haendel Doug Howe Erik Segerdell Sierra Taylor FlyBase: Micael Ashburner Rachel Drysdale George Gkoutos

3. 1.Goals Annotate mutant phenotypes Identify human disease models 2.Strategy 3.Progress

4. HumansAnimal models Mutant Gene Mutant or missing Protein Mutant Phenotype (disease) Mutant Gene Mutant or missing Protein Mutant Phenotype (disease model) Animal disease models:

5. HumansAnimal models Mutant Gene Mutant or missing Protein Mutant Phenotype (disease) Mutant Gene Mutant or missing Protein Mutant Phenotype (disease model) Animal disease models:

6. HumansAnimal models Mutant Gene Mutant or missing Protein Mutant Phenotype (disease) Mutant Gene Mutant or missing Protein Mutant Phenotype (disease model) Animal disease models:

7. 1.Goals Annotate mutant phenotypes Identify human disease models 2.Strategy 3.Progress

8. eyeplacementhypoteloric++ entityvalueattribute++ midfacedevelopmenthypoplastic+ + kidneysizehypertrophied+ + Phenotype (clinical sign) = P 1 = P 2 = P 3 = shh -/- (holoprosencephaly)

9. entityvalueattribute++ Phenotype (clinical sign) = Anatomical ontology Cell & tissue ontology Developmental ontology Gene ontology biological process molecular function cellular component + PATO (phenotype and trait ontology)

10. eyeplacementhypoteloric++ entityvalueattribute++ midfacedevelopmenthypoplastic+ + kidneysizehypertrophied+ + Phenotype (clinical sign) = P 1 = P 2 = P 3 = Syndrome = P 1 + P 2 + P 3 (disease) = holoprosencephaly

11. Human holo- prosencephaly Zebrafish shh Zebrafish oep

12. 1.Goals Annotate mutant phenotypes Identify human disease models 2.Strategy 3.Progress

13. OMIM genes ZFIN mutant genes FlyBase mutant genes

14. Data type Total Total ZFIN genes20,385 Genes with assigned human orthologs2,884 Genes with OMIM links2,174 Total ZFIN mutants3,188 ZFIN mutants with OMIM links Corresponding human genes Drosophila homologs of these 271 720 271 187

15. OMIM gene ZFIN gene FlyBase gene FlyBase mut pub ZFIN mut pub mouseratsno med OMIM disease LAMB1lamb1LanB1515439 - FECHfechFerro- chelatase 25929 Protoporphyria, Erythropoietic GLI2gli2aci388412722 - SLC4A1slc4a1CG817777719 Renal Tubular Acidosis, RTADR MYO7Amyo7ack84525316 Deafness; DFNB2; DFNA11 ALAS2alas2Alas17114 Anemia, Sideroblastic, X-Linked KCNH2kcnh2sei273112 - MYH6myh6Mhc1663612 Cardiomyopathy, Familial Hypertrophic; CMH TP53tp53p536433801911 Breast Cancer ATP2A1atp2a1Ca-P60A3261111 Brody Myopathy EYA1eya1eya251586 Branchiootorenal Dysplasia SOX10sox10Sox100B117 4 Waardenburg-Shah Syndrome

16. PATO development (underway) : Curator interface development (underway) Trial curation of ZFIN & FlyBase publications + OMIM (future)

17. PATO development (underway) : Anatomical Ontology cleanup PATO cleanup Curator interface development (underway) Trial curation of ZFIN & FlyBase publications + OMIM (future)

18. Resolving AO differences between ZFIN and FlyBase ZFIN: part start_stage (where stages are stored end_stage in separate ontology) FlyBase: stage1stage 2 … part1 part2

19. eyeplacementhypoteloric+ + eye hypoteloric+ EntityAttributeValue EntityAttribute

20. AO PATO Curator interface Trial curation

21. AO PATO Curator interface Trial curation User interface

22. PATO development (underway) : Anatomical Ontology cleanup PATO cleanup Initial curation of fish phenotypes - portable database for research labs CToL - taxonomy & phylogenies Curator interface development (underway) Trial curation of ZFIN & FlyBase publications + OMIM (future)

23. 1.Goals Annotate mutant phenotypes Identify human disease models 2.Strategy 3.Progress

24. Supported by NIH P41 HG002659 and U54 HG004028 the University of Oregon, Eugene, OR