Articles in 2021

Genome-wide association analyses using parental and offspring genotypes provide insights into fetal and maternal genetic effects on fetal growth. The results show that maternal and fetal genomes influence birth weight through distinct mechanisms.

Stephen T. Warren was a key contributor to the 1991 discovery of an unstable trinucleotide repeat that expands in families and causes loss of function in fragile X syndrome.

For most organisms, DNA sequences are available, but the complete RNA sequences are not. Here, we call for technologies to sequence full-length RNAs with all their modifications.

Haplotype-resolved genome assembly of an Oolong tea cultivar Tieguanyin and population genomic analyses of 190 Camellia accessions provide insights into the evolutionary history of the tea plant Camellia sinensis.

p53 activates Dux in mouse embryos and embryonic stem cells, as well as DUX4 in human facioscapulohumeral muscular dystrophy cell models.

The use of natural killer (NK) cells in immunotherapy as an alternative to allogeneic T cells is gaining ground. Here, two genome-scale high-throughput platforms are used to identify genes that modulate the sensitivity of multiple solid tumor cell lines to NK-mediated killing.

R-loops—nucleic acid structures composed of an RNA:DNA hybrid and displaced single-stranded DNA—are abundant in the genome and may impair progression of the replication fork, thus leading to accumulation of DNA damage and genome instability. A new study demonstrates that SWI/SNF chromatin-remodeling complexes are instrumental in resolving such R-loop-mediated transcription–replication conflicts, highlighting the importance of these chromatin remodelers in R-loop homeostasis and the maintenance of genome integrity.

An integrative analysis of single-nucleus assay for transposase-accessible chromatin with sequencing and RNA sequencing in normal and Alzheimer’s disease brain tissue identifies cell-type-specific cis-regulatory elements and candidate target genes at disease-associated loci.

Imputation of rare coding variants in the UK Biobank enables association and fine-mapping analyses of rare (minor allele frequency (MAF) = 0.00005) genotypes, identifying 600 new variant–trait associations, including long allelic series in individual genes.

Analysis of 129 N⁶-methyladenosine (m⁶A) profiles across 4 tissues (brain, lung, muscle and heart) identifies 8,843 tissue-specific and 469 tissue-shared m⁶A quantitative trait loci (QTLs). Of these, 184 m⁶A QTLs colocalize with GWAS signals.

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt βII-spectrin function and disturb cytoskeletal organization and dynamics.

Analysis of live-cell imaging and single-cell genome sequencing data of colorectal cancer organoids identifies temporal dynamics of sub-chromosomal copy-number amplifications.

The UK Biobank Exome Sequencing Consortium aims to sequence all the exomes of approximately 500,000 UK Biobank participants. This Perspective describes the results from approximately 200,000 exomes and discusses the lessons learned from this UK Biobank–biopharmaceutical company collaboration.

Genetic manipulation of poised enhancers (PEs) shows that orphan CpG islands promote physical and functional communication between PEs and distally located developmental genes.

The histone H3K4 methyltransferase SET1B is recruited to a subset of hypoxia-inducible genes by the HIF complex. Loss of SET1B reduces HIF transcriptional activity in hypoxia and impairs tumor formation in xenograft models.

An analytical framework based on transcriptome-wide association and electronic medical records provides insights into the relationship between plasma lipids and complex diseases on a phenome-wide scale.

PHYTOCHROME-INTERACTING FACTORs reshape the H2A.Z epigenetic landscape in response to light quality changes in Arabidopsis thaliana, through an interaction with the INO80 chromatin remodeling complex.

A large-scale genetic analysis of type 1 diabetes identifies new susceptibility variants, highlights potential regulatory mechanisms and provides genetic support for therapeutic targets for immune intervention.

Genome editing with CRISPR–Cas9 is beginning to be used clinically; promising results to date inspire hope for broad medical impact and mindfulness about safety. A new study shows that when Cas9 cuts its target, a fraction of the time, the target chromosome experiences a breakage process known as chromothripsis, thus prompting efforts to understand the potential negative consequences of this phenomenon and ways to mitigate them.

The decision to move back home was very appealing but still took substantial thought.