Browse Articles

DNA variants arising in the genome of cancer cells are a major cause of therapy failure, but for most variants, their effects on drug response are unknown. Base-editing screens provide a systematic approach to uncover the functions of cancer variants at scale, which might help to inform the use of precision cancer therapies.

Functional screens using mouse and human primary macrophages identify regulators of distinct inflammatory states, including a role for m6A mRNA modification in TNF production.

In the first-ever Undiagnosed Hackathon, nearly 100 experts from 28 countries combined advanced phenotyping and genomic techniques for 48 hours, ultimately providing diagnoses to 40% of the previously undiagnosed families. This inspiring model demonstrates the power of multidisciplinary collaboration and patient partnership in precision diagnostics.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

Chromosome-scale and haplotype-resolved assembly of Pinus densiflora sheds light on Pinus-specific genome enlargement. Comparison between haplotypes and resequencing of 30 wild accessions show allelic imbalance with roles in flowering regulation and stress resistance.

Base editing screens of 11 cancer genes identify four functional classes of variants that collectively underpin sensitivity and resistance to ten commonly used drugs in cancer cell lines.

Maize transcription factor TASSELSHEATH4 establishes the leaf versus meristem cell boundary and vegetative versus floral axillary meristem fates as part of a domestication gene network.

Genome-wide association analysis of gout and urate identifies 148 new loci, implicating biological pathways and prioritizing candidate genes involved in inflammatory processes.

Distinguishing ordinary diabetes from its monogenic forms has been one of the challenges in optimally managing the disease. Using high-quality imputation of rare variants and large databases, a study now defines the gray zone between the two and lays down a blueprint for objectively evaluating the related variants.

A pan-cancer genomic analysis finds an increase of extrachromosomal DNA (ecDNA) in treated and metastatic tumors compared to primary, untreated samples, as well as ecDNA features enriched in advanced disease.

This Perspective discusses approaches to generate ultimate genotypes, combining the best chromosome segments in livestock and crop populations, to increase key production, sustainability and welfare traits, compared with the current best individuals.

A new method called polymerase error rate sequencing (PER-seq) can measure the nucleotide misincorporation rate of DNA polymerases. DNA polymerase ε mutants produce an excess of CpG<TpG errors during DNA replication in a deamination-independent manner resembling the mutation spectrum in tumors.

C-to-T mutations in CpG dinucleotides are widespread in cancers and are also observed in normal cells. By developing and using a technique to quantify DNA polymerase errors (polymerase error rate sequencing, PER-seq), we reveal that C-to-T mutations in CpG dinucleotides constitute part of the error signature of both wild-type and mutant cancer-associated DNA polymerase ε.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Rare variant analyses identify a new type 2 diabetes risk allele near the LEP gene, which encodes leptin, and other risk alleles of intermediate penetrance in genes previously implicated in monogenic forms of diabetes.