Volume 54 Issue 11, November 2022

A new study identifies prolyl hydroxylation of histone H3 as a signal for the recruitment of KDM5A, altering H3K4me3 and gene expression. H3P16oh is independent of the HIF hypoxia-sensing pathway and provides a further layer of complexity to oxygen-sensitive chromatin modifications.

Genetic risk factors for autism include both rare and common variants. A study shows that rare copy number variants and common variants across 16p that contribute to autism risk functionally converge to downregulate the expression of a large group of neuronally expressed genes in the 16p subtelomeric region.

We present a high-resolution genomic variation map that greatly expands the sequence information for maize and its wild relatives in the Zea genus. Population genetics of Zea spp. provide a vast trove of adaptive alleles that are absent in maize, with the potential for accelerating future breeding by reintroducing genetic diversity.

Cancer cells frequently amplify oncogenes on DNA molecules outside of chromosomes — extrachromosomal DNA. A technique adapted for isolation of extrachromosomal DNA, termed CRISPR-CATCH, enables analyses of its genetic and epigenetic compositions, which provides insights into its origin, structural diversity and mechanism of oncogene activation in cancer.

Adult human kidney organoids or tubuloids are derived from an epithelial CD24⁺ subpopulation in the proximal nephron and can be utilized for advanced disease modeling of the most common hereditary kidney disease: autosomal dominant polycystic kidney disease.

The ability to predict gene-expression landscapes at single-cell resolution has long been a challenge in the field of genomics. We mapped whole-body single-cell transcriptomic landscapes of zebrafish, Drosophila, and earthworm using Microwell-seq. We propose the first sequence-based model, Nvwa, that can predict gene expression at single-cell resolution directly from genomic sequences.

Genome sequencing and analysis of public epigenomic data enabled the identification of disease-causing variants in a non-coding regulatory region of hexokinase 1 (HK1) in individuals with congenital hyperinsulinism. These variants caused inappropriate HK1 expression within pancreatic β-cells, which led to increased insulin secretion and hypoglycemia.

This Perspective addresses next steps to investigate the predictions that inhibition of APOBEC3-mediated mutagenesis may limit tumor heterogeneity, metastasis and drug resistance in a broad range of cancer types by highlighting gaps in our understanding of APOBEC3 biology in cancer and in healthy tissues and strategies to address them.

This study presents a method for constructing complex trait polygenic scores from rare variants and shows that a polygenic score combining common and rare variants improves the accuracy of diagnosis for type 2 diabetes based on hemoglobin A1C levels.

De novo variants altering a conserved region in an intron of HK1 cause congenital hyperinsulinism by perturbing the activity of a putative cell type-specific regulatory element.

Genome-wide analysis of self-reported dyslexia identifies 42 associated loci, including 27 not previously associated with cognitive traits. Dyslexia shows genetic correlation with ambidexterity but not neuroanatomical measures of language-related circuitry.

Common polygenic variation at chromosome 16p and rare recurrent deletions of 16p11.2 influencing autism risk are associated with reduced expression of genes throughout the 16p region, suggesting functional convergence of rare and common variant effects.

Multi-ancestry genome-wide association analyses identify 124 risk loci for rheumatoid arthritis, of which 34 are novel. A polygenic risk score based on multi-ancestry data showed comparable performance between populations of European and East Asian ancestries.

Genome-wide analyses identify loci associated with nonalcoholic fatty liver disease, including rare, protective loss-of-function variants in MTARC1 and GPAM. Plasma proteomic analyses provide insight into proteins involved in disease pathogenesis.

A genomic, transcriptomic and epigenomic analysis of chronic lymphocytic leukemia identifies genetic drivers and molecular subtypes associated with clinical outcomes.

Whole-genome sequencing of chronic lymphocytic leukemia from 485 patients identifies putative coding and noncoding drivers of disease. Genomically defined subgroups show distinct clinical and biological characteristics.

Adult kidney organoids, or tubuloids, originate from CD24⁺ epithelial cells. Tubuloids represent a functional kidney tubule and can be used to model autosomal dominant polycystic kidney disease and study drug response.

Ectopic imprinting control regions (ICRs) recapitulate chromatin states of endogenous imprinted loci in mouse embryonic stem cells. ATF7IP and ZMYM2 regulate epigenetic memory at ICRs.

Microwell-seq is used to generate single-cell, whole-body expression landscapes of zebrafish, Drosophila and earthworm. A deep-learning model, Nvwa, predicts gene expression from DNA sequence and identifies regulatory programs shared across eight species.

EGLN2 hydroxylates histone H3 at proline 16, enhancing the binding of KDM5A to H3K4me3. Genome- and transcriptome-wide analyses show that the EGLN2–KDM5A axis regulates target gene expression in mammalian cells.

A high-density genomic variation map from 744 genomes encompassing maize and all wild taxa of the genus Zea reveals evidence of adaptive variation and provides a genus-wide resource of genetic diversity in Zea.

CRISPR-CATCH is used to isolate extrachromosomal DNA (ecDNA) molecules containing oncogenes from human cancer cells. CRISPR-CATCH followed by nanopore sequencing allows for methylation profiling, highlighting differences from the native chromosomal loci.