Volume 53 Issue 6, June 2021

Single-cell and bulk transcriptomics of adult human microglia from a population of individuals reveals activated states across several brain disorders and maps Alzheimer’s disease variants to microglia-enriched genes.

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.

Numerous statistical models have been used to analyze single-cell RNA sequencing data. This Perspective proposes that a Poisson measurement model is sufficient and suitably flexible for this task, and its use would resolve current controversies.

Analysis of long-read sequencing data from 3,622 Icelanders identifies a set of high-confidence structural variants and provides insights into their effect on human traits and diseases.

A genome-wide survival study identifies variants at RIMS2 associated with progression of Parkinson’s disease to dementia and highlights divergence in the genetic architecture of disease onset and progression.

DNMT3A PWWP domain mutations promote localization of DNMT3A to CpG islands in a PRC1-dependent manner. DNMT3A interacts with H2AK119ub-modified nucleosomes.

A study of more than one million 23andMe research participants identifies genetic and nongenetic associations with COVID-19 susceptibility and severity.

Ultrafast Sample placement on Existing tRees (UShER) is an efficient method that facilitates the addition of new SARS-CoV-2 genome sequences onto the existing phylogeny, aiding in real-time analysis of viral evolution during the COVID-19 pandemic.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

A multivariate genome-wide association study highlighting loci that influence both face and brain shape suggesting shared developmental axes during early embryogenesis. These loci did not overlap with those governing behavioral–cognitive traits or neuropsychiatric risk indicating divergence between early brain development and cognitive function.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

A population-scale map of gene expression in primary human microglia provides a systematic exploration of microglia diversity and how age, sex, pathology, cortical anatomy and common germline genetic variation influence the microglia transcriptome.

An ABEmax-based screen identifies regulatory noncoding nucleotides in four loci that control erythroid fetal hemoglobin (HbF) expression. Targeting a repressor element raises HbF levels in cells from patients with sickle cell disease.

The transition from normal esophageal tissue to squamous carcinoma is characterized by an altered SOX2 cistrome. This transcriptional reprogramming activates endogenous retroviruses and double-stranded RNA expression, creating a dependency on the RNA editing enzyme ADAR1.

Chromothripsis, a chromosomal shattering event, can be elicited by micronuclei and chromosome bridges formed by CRISPR–Cas9-generated double-stranded breaks. Extensive chromosomal rearrangements may thus be an on-target effect of genome editing.

A plasma membrane transporter OsPHO1;2 coordinates phosphate reallocation essential for starch biosynthesis during grain filling of cereal crops, providing a potential breeding target for improving phosphate-use efficiency.

Genomic variations in 3,248 tetraploid cotton germplasms and multi-environmental genome-wide association analyses provide insights into the basis of geographic differentiation and fiber improvement in cultivated cotton.

Analysis of RNA-seq datasets from seven organs across seven species generates an alternative splicing (AS) atlas and shows that AS events provide functional gene diversification through generation of tissue- and time-specific transcript isoforms.