Linking Animal Models to Human Diseases Supported by

Linking Animal Models to Human Diseases Supported by NIH P 41 HG 002659 and U 54 HG 004028 the University of Oregon, Eugene, OR

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

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

Animal disease models: Humans Animal models Mutant Gene Mutant or missing Protein Mutant Phenotype (disease) Mutant Phenotype (disease model)

Animal disease models: Humans Animal models Mutant Gene Mutant or missing Protein Mutant Phenotype (disease) Mutant Phenotype (disease model)

Animal disease models: Humans Animal models Mutant Gene Mutant or missing Protein Mutant Phenotype (disease) Mutant Phenotype (disease model)

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

Phenotype (clinical sign) = entity + attribute + value + placement + hypoteloric P 1 = eye P 2 P 3 = midface + development + hypoplastic + hypertrophied = kidney + size shh-/(holoprosencephaly)

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

Phenotype (clinical sign) = entity + attribute + value + placement + hypoteloric P 1 = eye P 2 P 3 = midface + development + hypoplastic + hypertrophied = kidney + size Syndrome = P 1 + P 2 + P 3 (disease) = holoprosencephaly

Human holoprosencephaly Zebrafish shh Zebrafish oep

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

OMIM genes ZFIN mutant genes Fly. Base mutant genes

Data type Total ZFIN genes Genes with assigned human orthologs Genes with OMIM links Total ZFIN mutants with OMIM links Corresponding human genes Drosophila homologs of these 271 Total 20, 385 2, 884 2, 174 3, 188 720 271 187

OMIM gene ZFIN gene LAMB 1 lamb 1 FECH Fly. Base gene Fly. Base mut pub ZFIN mut pub mouse Lan. B 1 5 15 fech Ferrochelatase 2 GLI 2 gli 2 a ci SLC 4 A 1 slc 4 a 1 MYO 7 A rat sno med OMIM disease 4 39 - 5 9 29 Protoporphyria, Erythropoietic 388 41 27 22 - CG 8177 7 19 Renal Tubular Acidosis, RTADR myo 7 a ck 84 5 25 16 Deafness; DFNB 2; DFNA 11 ALAS 2 alas 2 Alas 1 7 1 14 Anemia, Sideroblastic, X-Linked KCNH 2 kcnh 2 sei 27 3 1 12 - MYH 6 myh 6 Mhc 166 3 6 12 Cardiomyopathy, Familial Hypertrophic; CMH TP 53 tp 53 64 3 380 19 11 Breast Cancer ATP 2 A 1 atp 2 a 1 Ca-P 60 A 32 6 1 1 11 Brody Myopathy EYA 1 eya 251 5 8 6 Branchiootorenal Dysplasia SOX 10 sox 10 Sox 100 B 1 17 17 4 Waardenburg-Shah Syndrome 3

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

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

Resolving AO differences between ZFIN and Fly. Base ZFIN: part start_stage (where stages are stored end_stage Fly. Base: stage 1 stage 2 … part 1 part 2 in separate ontology)

Entity eye + Entity Attribute Value placement + hypoteloric Attribute eye + hypoteloric

AO PATO Trial curation Curator interface

AO PATO Trial curation Curator interface User interface

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

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

Supported by NIH P 41 HG 002659 and U 54 HG 004028 the University of Oregon, Eugene, OR