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

Nature, Год журнала: 2023, Номер 625(7993), С. 92 - 100

Опубликована: Дек. 6, 2023

Язык: Английский

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Structural variation in the sequencing era

Nature Reviews Genetics, Год журнала: 2019, Номер 21(3), С. 171 - 189

Опубликована: Ноя. 15, 2019

Язык: Английский

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Methods for mapping 3D chromosome architecture

Nature Reviews Genetics, Год журнала: 2019, Номер 21(4), С. 207 - 226

Опубликована: Дек. 17, 2019

Язык: Английский

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Visualizing DNA folding and RNA in embryos at single-cell resolution

Nature, Год журнала: 2019, Номер 568(7750), С. 49 - 54

Опубликована: Март 18, 2019

Язык: Английский

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Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression

Nature Genetics, Год журнала: 2019, Номер 51(8), С. 1272 - 1282

Опубликована: Июль 15, 2019

Язык: Английский

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Functional dissection of the Sox9–Kcnj2 locus identifies nonessential and instructive roles of TAD architecture

Nature Genetics, Год журнала: 2019, Номер 51(8), С. 1263 - 1271

Опубликована: Июль 29, 2019

Язык: Английский

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A genome-wide mutational constraint map quantified from variation in 76,156 human genomes

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Март 21, 2022

Abstract 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 assess constraint for non-protein-coding regions have proven more difficult. Here we aggregate, process, and release a dataset 76,156 genomes from the Genome Aggregation Database (gnomAD), largest public open-access genome reference dataset, use this build mutational map whole genome. We present refined model that incorporates local sequence context regional genomic features detect depletions across As expected, proteincoding sequences overall are under stronger than non-coding regions. Within genome, constrained enriched known regulatory elements variants implicated in complex diseases traits, facilitating triangulation biological annotation, disease association, DNA analysis. More tend regulate genes, while captures additional functional information underrecognized gene metrics. demonstrate genome-wide provides an effective approach characterizing improving identification interpretation genetic variation.

Язык: Английский

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The Unfolded Protein Response: Detecting and Responding to Fluctuations in the Protein-Folding Capacity of the Endoplasmic Reticulum

Cold Spring Harbor Perspectives in Biology, Год журнала: 2019, Номер 11(9), С. a033886 - a033886

Опубликована: Янв. 22, 2019

Most of the secreted and plasma membrane proteins are synthesized on membrane-bound ribosomes endoplasmic reticulum (ER). They require engagement ER-resident chaperones foldases that assist in their folding maturation. Since protein homeostasis ER is crucial for cellular function, protein-folding status organelle's lumen continually surveyed by a network signaling pathways, collectively called unfolded response (UPR). Protein-folding imbalances, or "ER stress," detected highly conserved sensors adjust ER's capacity according to physiological needs cell. We review recent developments field have provided new insights into stress-sensing mechanisms used UPR which they integrate various inputs organelle accommodate fluctuations demands.

Язык: Английский

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Genome assembly of a tropical maize inbred line provides insights into structural variation and crop improvement

Nature Genetics, Год журнала: 2019, Номер 51(6), С. 1052 - 1059

Опубликована: Май 31, 2019

Maize is one of the most important crops globally, and it shows remarkable genetic diversity. Knowledge this diversity could help in crop improvement; however, gold-standard genomes have been elucidated only for modern temperate varieties. Here, we present a high-quality reference genome (contig N50 15.78 megabases) maize small-kernel inbred line, which derived from tropical landrace. Using haplotype maps B73, Mo17 SK, identified 80,614 polymorphic structural variants across 521 diverse lines. Approximately 22% these not be detected by traditional single-nucleotide-polymorphism-based approaches, some them affect gene expression trait performance. To illustrate utility SK used to perform map-based cloning major effect quantitative locus controlling kernel weight—a key selected during improvement. The underlying candidate ZmBARELY ANY MERISTEM1d provides target increasing yields. A line analyses between two other genomes, B73 Mo17, provide insights into variation

Язык: Английский

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Microscopy-Based Chromosome Conformation Capture Enables Simultaneous Visualization of Genome Organization and Transcription in Intact Organisms

Molecular Cell, Год журнала: 2019, Номер 74(1), С. 212 - 222.e5

Опубликована: Фев. 19, 2019

Язык: Английский

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