Browse Articles

Mouse models of lung and colorectal cancer with sporadic DNA mismatch repair deficiency clarify that the intratumor heterogeneity and clonal architecture rather than tumor mutational burden are powerful determinants of immunotherapy response.

Using data from the UK Biobank, we reveal the roles of selection and mutation in shaping the genetic diversity of mosaic chromosomal alterations in healthy blood.

A survey of the fitness effects conferred by mosaic chromosomal alterations (mCAs) in UK Biobank shows that most mCAs—despite being relatively infrequent—are associated with increased fitness. Mosaic loss of the sex chromosomes was more common but these events afforded only small fitness gains.

Genome-wide association analyses of blood glucose measurements under nonstandardized conditions provide insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.

Resequencing of 2,839 hybrid rice cultivars and 9,839 F₂ individuals from 18 elite crosses is used to characterize the genetics underlying a range of grain yield-related traits, providing insights into heterosis during breeding and a predictive model.

Transformation of a myeloproliferative neoplasm to a secondary acute myeloid leukemia is rare but devastating. Single-cell, multi-omic characterization of hematopoietic stem and progenitor cells now shows the role of inflammation in transformation driven by mutations in TP53, with effects on the mutant clone but also non-mutant counterparts.

The symmetric inheritance of histone modifications by the nascent chromatin fibers during DNA replication is essential for proper developmental progression. Two new studies using mouse embryonic stem cells further illuminate the role of histone inheritance in early cell fate decisions.

Asymmetric segregation of parental histones H3 and H4 in MCM2-mutant embryonic stem cells impacts mitotic inheritance of histone modifications and genome regulation. MCM2-2A mutation perturbs exit from pluripotency and differentiation.

Mcm2 mutation or Pole3 deletion in mouse embryonic stem cells leads to asymmetric parental histone distribution and impaired neural differentiation. Mutation of the Mcm2 histone-binding domain causes defects in pre-implantation development and embryonic lethality.

Single-cell multi-omic analyses show that chronic inflammation contributes to myeloproliferative neoplasm transformation to secondary acute myeloid leukemia by enhancing tumor protein 53 (TP53) mutant cell fitness and genetic evolution.

In this issue of Nature Genetics, Lara-Astiaso et al. systematically characterized the functional roles of several chromatin factors in hematopoiesis by combining functional CRISPR screens with single-cell transcriptomics and chromatin accessibility profiling, revealing lineage biases and relationships with important transcription factors.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

High-quality genome assemblies of four Solanum Americanum accessions lead to the identification of three NLR-encoding genes, Rpi-amr4, R02860 and R04373, that recognize potato late blight pathogen Phytophthora infestans effectors.

Linkage disequilibrium graphical models (LDGMs) derived from genome-wide genealogies provide an efficient representation of LD, yielding large improvements in runtime for LD matrix computations. LDGMs will enable methods that scale to millions of variants and individuals.

An analysis of UK Biobank participants shows that the risk of developing different types of myeloid neoplasms can be inferred years before diagnosis. The authors integrate somatic gene mutations with blood test parameters into a predictive model, which could guide future strategies for early detection and prevention of these diseases.