23 papers · ranked by Valyu relevance
Edwin G. Peña-Martínez, José A. Rodríguez-Martínez
Genome-wide association studies (GWAS) have mapped over 90% of disease- and quantitative-trait-associated variants within the non-coding genome. Non-coding regulatory DNA (e.g., promoters and enhancers) and RNA (e.g., 5′ and 3′ UTRs and splice sites) are essential in regulating temporal and tissue-specific gene…
Jamie M. Ellingford, Joo Wook Ahn, Richard D. Bagnall, Diana Baralle + 23 more
'Stephanie Barton' 'Chris Campbell' 'Kate Downes' 'Sian Ellard' 'Celia Duff-Farrier' 'David R. FitzPatrick' 'John M. Greally' 'Jodie Ingles' 'Neesha Krishnan' 'Jenny Lord' 'Hilary C. Martin' 'William G. Newman' 'Anne O’Donnell-Luria' 'Simon C. Ramsden' 'Heidi L. Rehm' 'Ebony Richardson' 'Moriel Singer-Berk' 'Jenny C.…
Siwei Chen, Laurent C. Francioli, Julia K. Goodrich, Ryan L. Collins + 41 more
The depletion of disruptive variation caused by purifying natural selection (constraint) has been widely used to investigate protein-coding genes underlying human disorders, but attempts to assess constraint for non-protein-coding regions have proven more difficult. Here we aggregate, process, and release a dataset of…
Efthalia Moustakli, Nektaria Zagorianakou, Stylianos Makrydimas, Andreas Miltiadous + 3 more
Analysis of coding areas has long been used to study monogenic illnesses, but despite the extensive use of whole-exome sequencing (WES), up to half of suspected cases remain genetically unexplained. Variants outside coding areas can alter splicing, transcript stability, or gene regulation, compromising normal gene…
Martin Kircher, Kerstin U. Ludwig
Identification of genetic variation in individual genomes is now a routine procedure in human genetic research and diagnostics. For many variants, however, insufficient evidence is available to establish a pathogenic effect, particularly for variants in non-coding regions. Furthermore, the sheer number of candidate…
Xin Li, Stephen B. Montgomery
Advances in genome sequencing are providing unprecedented resolution of rare and private variants. However, methods which assess the effect of these variants have relied predominantly on information within coding sequences. Assessing their impact in non-coding sequences remains a significant contemporary challenge. In…
Julia di Iulio, Istvan Bartha, Emily H.M. Wong, Hung-Chun Yu + 11 more
Large scale efforts to sequence whole human genomes provide extensive data on the non-coding portion of the genome. We used variation information from 11,257 human genomes to describe the spectrum of sequence conservation in the population. We established the genome-wide variability for each nucleotide in the context…
David Castellano, Adam Eyre-Walker, Kasper Munch
DNA diversity varies across the genome of many species. Variation in diversity across a genome might arise from regional variation in the mutation rate, variation in the intensity and mode of natural selection, and regional variation in the recombination rate. We show that both non-coding and non-synonymous diversity…
Slavé Petrovski, Ayal B. Gussow, Quanli Wang, Matt Halvorsen + 5 more
'Yujun Han' 'William H. Weir' 'Andrew S. Allen' 'David B. Goldstein' 'Chris Cotsapas'] Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at…
Thilona Arumugam, Theolan Adimulam, Anmol Gokul, Veron Ramsuran
Variation within the non-coding genome may influence the regulation and expression of important genes involved in immune control such as the human leukocyte antigen (HLA) system. Class I and Class II HLA molecules are essential for peptide presentation which is required for T lymphocyte activation. Single nucleotide…
Sean Whalen, Katherine S. Pollard
Linkage disequilibrium (LD) and genomic proximity are commonly used to map non-coding variants to genes, despite increasing examples of causal variants outside the LD block of the gene they regulate. We compared chromatin contacts in 22 cell types to LD across billions of pairs of loci in the human genome and found no…
David Curtis
UK Biobank has released whole genome sequence data for 500,000 participants, including allele counts for hundreds of millions of variants and these were considered in the context of the pentanucleotide background on which they occurred. Variants with an allele count of 25 were found to closely mirror previously…
Dan Graur
Because genomes are products of natural processes rather than "intelligent design," all genomes contain functional and nonfunctional parts. The fraction of the genome that has no biological function is called "rubbish DNA." Rubbish DNA consists of "junk DNA," i.e., the fraction of the genome on which selection does not…
Arthur J Jallet, Antonin Demange, Fiona Leblay, Mathilde Decourcelle + 3 more
The frequency of synonymous codons in protein coding genes is non-random and varies both between species and between genes within species. Whether this codon usage bias (CUBias) reflects underlying neutral mutational processes or is instead shaped by selection remains an open debate, especially regarding the role of…
Authors not listed
We present a chemical framework in which adaptive organization is achieved by tuning a gated quantum resonator (adaptive genomic resonator) {driven quantum oscillator} across a driven, dissipative reaction manifold (fitness landscape) {Hamiltonian potential surface}. In this view, catalytic elements set gain and phase…
M. Johnsson
This paper will argue that one of the biggest challenges for livestock genomics is to make whole-genome sequencing and functional genomics applicable to breeding practice. It discusses potential explanations for why it is so difficult to consistently improve the accuracy of genomic prediction by means of wholegenome…
Fuchun Lin, Ling San, Safavi-Naini Reihaneh, Huaxiong Wang
—Non-malleable codes protect against an adversary who can tamper with the coded message by using a tampering function in a specified function family, guaranteeing that the tampering result will only depend on the chosen function and not the coded message. The codes have been motivated for providing protection against…
Kuba Nowak, Paweł Błażej, Małgorzata Wnetrzak, Dorota Mackiewicz + 1 more
Reprogramming of the standard genetic code in order to include non-canonical amino acids (ncAAs) opens a new perspective in medicine, industry and biotechnology. There are several methods of engineering the code, which allow us for storing new genetic information in DNA sequences and transmitting it into the protein…
Authors not listed
One aim of the international Human Proteome Organization (HUPO) Human Proteome Project (HPP) is to obtain high-confidence translation evidence for every human protein-coding gene established in its target list of 19433 entries based on the protein-coding genes from Ensembl-GENCODE. However, 76 are annotated in…
Ying Chen Eyre‐Walker, Adam Eyre‐Walker
We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have…
Stefanie Mühlhausen, Peggy Findeisen, Uwe Plessmann, Henning Urlaub + 1 more
The genetic code is the universal cellular translation table to convert nucleotide into amino acid sequences. Changes to sense codons are expected to be highly detrimental. However, reassignments of single or multiple codons in mitochondria and nuclear genomes demonstrated that the code can evolve. Still, alterations…
Matheus Henrique Pimenta-Zanon, André Yoshiaki Kashiwabara, André Luís Laforga Vanzela, Fabrício Martins Lopes
based on the Principle of Maximum Entropy Authors: ['Matheus Henrique Pimenta-Zanon' 'André Yoshiaki Kashiwabara' 'André Luís Laforga Vanzela' 'Fabrício Martins Lopes'] Advances in high throughput sequencing technologies provide a large number of genomes to be analyzed, so computational methodologies play a crucial…
Benjamin King, Max Winokan, Paul Stevenson, Jim Al-Khalili + 2 more
The adenine-thymine tautomer (A-T) has previously been discounted as a spontaneous mutagenesis mechanism due to the energetic instability of the tautomeric configuration. We study the stability of A-T while the nucleobases undergo DNA strand separation. Our calculations indicate an increase in the stability of A-T as…