Articles in 2021

Mutagenesis of 23 ultraconserved enhancers and examination of their activities in transgenic mouse reporter assays show that overall their regulatory properties are robust to mutation. Manipulation of endogenous loci in mice corroborates reporter assay data.

Individuals with SYK gain-of-function variants develop immunodeficiency and systemic inflammation, which are recapitulated in a knock-in mouse model. Treatment of these mice with bone marrow transplantation or with a SYK inhibitor ameliorates disease symptoms, highlighting potential therapeutic strategies for patients with SYK mutations.

A single-cell transcriptomic analysis of neuroblastomas and healthy adrenal glands defines cell types and lineage trajectories during different developmental stages. Comparisons with the transcriptomes of neuroblastoma cells show that their transcriptomes most closely resemble those of developing neuroblasts of the adrenal gland.

A pediatric cancer dependency map generated with genome-scale CRISPR–Cas9 loss-of-function screens in 82 pediatric cancer cell lines highlights genetic dependencies across a range of tumor types.

A high-quality genome assembly of Weining rye sheds new light on gene duplications and their effects on starch biosynthesis genes, gene expression features underlying early heading trait and putative domestication-associated chromosomal regions.

A chromosome-scale genome assembly of rye inbred line ‘Lo7’ provides insights into its incomplete genetic isolation from wild relatives, mechanisms of genome structural evolution and the yield benefits of rye–wheat introgressions.

Human–chimpanzee tetraploid fusions serve as a model to study gene expression differences between these species, allowing for separation of cis- from trans-regulatory effects and analysis of unique craniofacial morphologies.

We present the Polygenic Score (PGS) Catalog (https://www.PGSCatalog.org), an open resource of published scores (including variants, alleles and weights) and consistently curated metadata required for reproducibility and independent applications. The PGS Catalog has capabilities for user deposition, expert curation and programmatic access, thus providing the community with a platform for PGS dissemination, research and translation.

A new study builds a novel deep-learning approach to unravel the syntax of transcription-factor binding from high-resolution ChIP–nexus data. In silico simulations lead to experimental validation of complex sequence-based predictions: helical periodicity and directional cooperativity between transcription factors.

It’s time for a paradigm shift in the scientific enterprise. Our social responsibilities, especially as stakeholders in a field such as genetics, are central to the responsible conduct of research.

Chromosomal inversions frequently underlie distinct phenotypic variation. A new study shows that in butterflies, inversion haplotypes accumulate deleterious mutations that prevent fixation in natural populations.

Genome-wide CRISPR screens for proviral host factors of SARS-CoV-2 and HCoV-229E human coronaviruses show that the lysosomal protein TMEM106B is required for SARS-CoV-2 infection.

Identification of the genetic differences between two different disorders has been hampered by a need for individual-level data from cases of both disorders. CC-GWAS enables the comparison of allele frequencies among cases of two disorders using case–control GWAS summary statistics.

Integrative data analysis of 1,367 human iPSC lines maps common and rare regulatory variants that colocalize with loci associated with human traits and diseases.

Single-cell RNA-seq analysis of iPSC neural differentiation identifies markers that predict line-to-line differences in cell fate potential and eQTLs that are specific to different stages of differentiation and that overlap with GWAS risk variants for neurological traits.

CRISPR–Cas9 tiled screens of the β-globin gene cluster identify an NF-Y bound activator element at the γ-globin promoter. Binding competition by the transcriptional repressor BCL11A leads to NF-Y eviction and a switch from fetal to adult globin gene expression.