Structure, function, and pharmacology of glutamate receptor ion channels

KB Hansen, LP Wollmuth, D Bowie, H Furukawa… - Pharmacological …, 2021 - ASPET
Many physiologic effects of l-glutamate, the major excitatory neurotransmitter in the
mammalian central nervous system, are mediated via signaling by ionotropic glutamate …

Genomics, convergent neuroscience and progress in understanding autism spectrum disorder

HR Willsey, AJ Willsey, B Wang… - Nature Reviews …, 2022 - nature.com
More than a hundred genes have been identified that, when disrupted, impart large risk for
autism spectrum disorder (ASD). Current knowledge about the encoded proteins—although …

A genomic mutational constraint map using variation in 76,156 human genomes

S Chen, LC Francioli, JK Goodrich, RL Collins, M Kanai… - Nature, 2024 - nature.com
The depletion of disruptive variation caused by purifying natural selection (constraint) has
been widely used to investigate protein-coding genes underlying human disorders,,–, but …

The mutational constraint spectrum quantified from variation in 141,456 humans

KJ Karczewski, LC Francioli, G Tiao, BB Cummings… - Nature, 2020 - nature.com
Genetic variants that inactivate protein-coding genes are a powerful source of information
about the phenotypic consequences of gene disruption: genes that are crucial for the …

Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes

KJ Karczewski, LC Francioli, G Tiao, BB Cummings… - biorxiv, 2019 - biorxiv.org
Genetic variants that inactivate protein-coding genes are a powerful source of information
about the phenotypic consequences of gene disruption: genes critical for an organism's …

Gene expression across mammalian organ development

M Cardoso-Moreira, J Halbert, D Valloton, B Velten… - Nature, 2019 - nature.com
The evolution of gene expression in mammalian organ development remains largely
uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum …

Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study

S Petrovski, V Aggarwal, JL Giordano, M Stosic, K Wou… - The Lancet, 2019 - thelancet.com
Background Identification of chromosomal aneuploidies and copy number variants that are
associated with fetal structural anomalies has substantial value. Although whole-exome …

Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug …

EA King, JW Davis, JF Degner - PLoS genetics, 2019 - journals.plos.org
Despite strong vetting for disease activity, only 10% of candidate new molecular entities in
early stage clinical trials are eventually approved. Analyzing historical pipeline data, Nelson …

[HTML][HTML] A cross-disorder dosage sensitivity map of the human genome

RL Collins, JT Glessner, E Porcu, M Lepamets… - Cell, 2022 - cell.com
Rare copy-number variants (rCNVs) include deletions and duplications that occur
infrequently in the global human population and can confer substantial risk for disease. In …

Multi-platform discovery of haplotype-resolved structural variation in human genomes

MJP Chaisson, AD Sanders, X Zhao, A Malhotra… - Nature …, 2019 - nature.com
The incomplete identification of structural variants (SVs) from whole-genome sequencing
data limits studies of human genetic diversity and disease association. Here, we apply a …