We investigated the distribution of PTVs, variants predicted to disrupt protein-coding genes through the introduction of a stop codon, frameshift, or the disruption of an essential splice site; such variants are
Here we present a catalogue of human protein-coding variation, derived from exome sequencing of 983,578 individuals across diverse populations. In total, 23% of the Regeneron Genetics Center Million Exome (RGC-ME) data come from individuals of African, East Asian, Indigenous American, Middle ...
Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to dete...
Compelling evidence suggests that human cognitive function is strongly influenced by genetics. Here, we conduct a large-scale exome study to examine whether rare protein-coding variants impact cognitive function in the adult population (n = 485,930). We identify eight genes (ADGRB2,KDM5B,GI...
Here, we sequenced to a high coverage the Danish Holstein cattle breed to detect and characterize single nucleotide polymorphisms (SNPs), insertion/deletions (Indels), and loss-of-function (LoF) variants in protein-coding genes in order to provide a comprehensive resource for subsequent detection ...
1b,c), PINNACLE generates contextualized protein representations that are tailored to cell types in which protein-coding genes are activated (Fig. 1d). Unlike context-free models, PINNACLE produces multiple representations for every protein, each contingent on its specific cell type context. ...
Most known pathogenic mutations occur in protein-coding regions of DNA and change the way proteins are made. Taking protein structure into account has therefore provided great insight into the molecular mechanisms underlying human genetic disease. While there has been much focus on how mutations can ...
(B) Both uORFs of the main 5′ UTR (GRN_NM002087) are in-frame with the canonical ATG of the GRN coding sequence and share the same STOP codon. All 3 predicted uORFs of the alternative spliced 5′ UTR (GRN_XM005257253) are in different frames and uORF5 is in-frame with the ...
Only protein coding genes with documented author and Pubmed reference were included. The resulting network consisted of N = 15847 proteins connected via M = 259196 edges. Mapping our hits on this network, we got a subnetwork consisting of N = 77 proteins connected via M = 76 edges. In ...
(Fig.1b,c),PINNACLEgenerates contextualized protein representations that are tailored to cell types in which protein-coding genes are activated (Fig.1d). Unlike context-free models,PINNACLEproduces multiple representations for every protein, each contingent on its specific cell type context. ...