11 papers · ranked by Valyu relevance
Beibei Wang, Siyuan Song, Song Cheng, Yihang Lin + 3 more
The rapid expansion of whole-genome sequencing (WGS) has highlighted the important contribution of noncoding variants to human disease, yet their pathogenic mechanisms remain difficult to resolve. Traditional statistical and experimental approaches often struggle to capture complex regulatory interactions or establish…
Jordan S Kesner, Ziheng Chen, Alexis A Aparicio, Xuebing Wu
Translation is pervasive outside of canonical coding regions, occurring in lncRNAs, UTRs, and introns. While the resulting polypeptides are often non-functional, translation in noncoding regions is nonetheless necessary for the birth of new coding regions. The mechanisms underlying the surveillance of translation in…
Alexander L. Han, Chloe F. Sands, Dorota Matelska, Jessica C. Butts + 9 more
Rapidly expanding genomic databases have enabled the identification of regions in the human genome intolerant to variation and thus likely relevant to human disease. However, despite their unprecedented scale, these datasets remain constrained by limited ancestral diversity. Here, we systematically evaluate how genetic…
Yuncheng Duan, Constantine Stavrianidis, Grace Tzun-Wen Shaw, Christopher Sottolano + 5 more
A key problem in genetics is associating variants with disease phenotypes. In aid of this, much progress has been made in quantifying the functional impact of individual variants on the gene product it codes for. However, the intolerance of the sequence in which those variants are found to functional variation is also…
Peiguo Shi, Feiyue Yang, FNU Tala, Wesley Huang + 9 more
The human genome is dominated by noncoding sequences, most of which are poorly conserved across species. How genetic information is distributed between coding and noncoding regions remains a fundamental unresolved question. Using CRISPR saturation mutagenesis at base-pair resolution, we mapped the functional fitness…
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…
Zilin Li, Xihao Li, Hufeng Zhou, Sheila M. Gaynor + 57 more
Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare variants’ (RVs) associations with complex human traits. Variant set analysis is a powerful approach to study RV association, and a key component of it is constructing RV sets for analysis. However, existing methods have limited ability…
James A. Shapiro
This is a commentary on the article by Eviatar Nevo and Kexin Li entitled “Sympatric Speciation in Mole Rats and Wild Barley and Their Genome Repeatome Evolution: A Commentary”, published recently in Advanced Genetics.
IGVF Consortium
Our genomes influence nearly every aspect of human biology from molecular and cellular functions to phenotypes in health and disease. Human genetics studies have now associated hundreds of thousands of differences in our DNA sequence ("genomic variation") with disease risk and other phenotypes, many of which could…
Anyou Wang
The mechanisms underlying lifespan evolution in organisms have long been mysterious. However, recent studies have demonstrated that organisms evolutionarily gain noncoding RNAs (ncRNAs) that carry endogenous profound functions in higher organisms1,2, including lifespan3 . This study unveils ncRNAs as crucial drivers…
Dylan De Groote, Daniele Pepe, Xander Janssens, Kim De Keersmaecker
Accurate annotation of genetic variants-distinguishing whether they affect protein-coding or noncoding genomic regions-is crucial for evaluating their potential role in disease development. Prominent examples have been identified of variants that for many years had been considered to be coding missense or synonymous…