Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium.

Although next-generation sequencing has revolutionized the ability to associate variants with human diseases, diagnostic rates and development of new therapies are still limited by a lack of knowledge of the functions and pathobiological mechanisms of most genes. To address this challenge, the International Mouse Phenotyping Consortium is creating a genome- and phenome-wide catalog of gene function by characterizing new knockout-mouse strains across diverse biological systems through a broad set of standardized phenotyping tests. All mice will be readily available to the biomedical community. Analyzing the first 3,328 genes identified models for 360 diseases, including the first models, to our knowledge, for type C Bernard-Soulier, Bardet-Biedl-5 and Gordon Holmes syndromes. 90% of our phenotype annotations were novel, providing functional evidence for 1,092 genes and candidates in genetically uncharacterized diseases including arrhythmogenic right ventricular dysplasia 3. Finally, we describe our role in variant functional validation with The 100,000 Genomes Project and others.

Crossed Aphasia in a Patient with Anaplastic Astrocytoma of the Non-Dominant Hemisphere.

Aphasia describes a spectrum of speech impairments due to damage in the language centers of the brain. Insult to the inferior frontal gyrus of the dominant cerebral hemisphere results in Broca's aphasia - the inability to produce fluent speech. The left cerebral hemisphere has historically been considered the dominant side, a characteristic long presumed to be related to a person's "handedness". However, recent studies utilizing fMRI have shown that right hemispheric dominance occurs more frequently than previously proposed and despite a person's handedness. Here we present a case of a right-handed patient with Broca's aphasia caused by a right-sided brain tumor. This is significant not only because the occurrence of aphasia in right-handed-individuals with right hemispheric brain damage (so-called "crossed aphasia") is unusual but also because such findings support dissociation between hemispheric linguistic dominance and handedness.