title: Disease insights through cross-species phenotype comparisons.
abstract: New sequencing technologies have ushered in a new era for diagnosis and discovery of new causative mutations for rare diseases. However, the sheer numbers of candidate variants that require interpretation in an exome or genomic analysis are still a challenging prospect. A powerful approach is the comparison of the patient's set of phenotypes (phenotypic profile) to known phenotypic profiles caused by mutations in orthologous genes associated with these variants. The most abundant source of relevant data for this task is available through the efforts of the Mouse Genome Informatics group and the International Mouse Phenotyping Consortium. In this review, we highlight the challenges in comparing human clinical phenotypes with mouse phenotypes and some of the solutions that have been developed by members of the Monarch Initiative. These tools allow the identification of mouse models for known disease-gene associations that may otherwise have been overlooked as well as candidate genes may be prioritized for novel associations. The culmination of these efforts is the Exomiser software package that allows clinical researchers to analyse patient exomes in the context of variant frequency and predicted pathogenicity as well the phenotypic similarity of the patient to any given candidate orthologous gene.
authors.affiliation: University Library and Department of Medical Informatics and Epidemiology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Haendel
authors.affiliation: University Library and Department of Medical Informatics and Epidemiology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Vasilevsky
authors.affiliation: University Library and Department of Medical Informatics and Epidemiology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brush
authors.affiliation: Department of Biomedical Informatics and Intelligent Systems Program, University of Pittsburgh, Pittsburgh, PA, 15206, USA.
authors.forename: Harry S
authors.initials: HS
authors.lastname: Hochheiser
authors.affiliation: Skarnes Faculty Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Julius
authors.initials: J
authors.lastname: Jacobsen
authors.affiliation: Skarnes Faculty Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Anika
authors.initials: A
authors.lastname: Oellrich
authors.affiliation: Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA, 94720, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Mungall
authors.affiliation: Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA, 94720, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Washington
authors.affiliation: Computational Biology Group, Institute for Medical Genetics and Human Genetics, Universitatsklinikum Charité, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Köhler
authors.affiliation: Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA, 94720, USA.
authors.forename: Suzanna E
authors.initials: SE
authors.lastname: Lewis
authors.affiliation: Computational Biology Group, Institute for Medical Genetics and Human Genetics, Universitatsklinikum Charité, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Robinson
authors.affiliation: Skarnes Faculty Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. ds5@sanger.ac.uk.
authors.forename: Damian
authors.identifier: http://orcid.org/0000-0002-5836-9850
authors.initials: D
authors.lastname: Smedley
mesh_terms: D000818:Animals; D019295:Computational Biology; D030541:Databases, Genetic; D004195:Disease Models, Animal; D059472:Exome / Q000235:genetics; D030342:Genetic Diseases, Inborn; D023281:Genomics; D006801:Humans; D051379:Mice; D009154:Mutation; D010641:Phenotype