Volume 54 Issue 5, May 2022

To leverage the genetic diversity in Nigeria, we established the Non-Communicable Diseases Genetic Heritage Study (NCD-GHS) consortium to help produce a comprehensive catalog of human genetic variation in Nigeria and assess the burden and etiological characteristics of non-communicable diseases in 100,000 adults in Nigeria.

A new study demonstrates that the disordered N-terminal domain of DNMT3A1 binds PRC1-catalyzed H2AK119ub, targeting DNA methylation to bivalent promoters in mouse brain cortical cells. Methylation around bivalent genes is critical for mouse postnatal development, and could be equally important in other cell types and in disease.

The genome of the SunUp transgenic papaya cultivar includes a complex 1.64-Mb insertion that contains 3 transgenic fragments integrated with 61 nuclear genome fragments from the progenitor Sunset cultivar and 13 organelle genome fragments. Population genomic analyses yielded 147 selective sweeps during papaya domestication, which include essential genes that are involved in fruit flesh color formation and sugar content.

Exome sequencing analysis of 13,933 individuals with bipolar disorder finds enrichment of ultra-rare protein-truncating variants in constrained genes. Combined analysis with schizophrenia exome data identifies AKAP11 as a risk gene for both disorders.

Joint analysis of 11 major psychiatric disorders identifies four broad factor underlying genetic correlations among the disorders. Association analyses detect 152 loci acting on these factors and identify 9 loci that act heterogeneously across disorders.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

PRS-CSx is a polygenic risk score construction method that improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations.

Within-sibship genome-wide association analyses using data from 178,076 siblings illustrate differences between population-based and within-sibship GWAS estimates for phenotypes influenced by demographic and indirect genetic effects.

Analyses of cis-genetic regulation of the plasma proteome in European and African American populations lead to the identification of shared and unique cis-protein quantitative trait loci and models for proteome-wide association studies of complex traits.

Integrating methods that assess allele-specific regulatory activity and chromatin accessibility in T cells identifies putative causal variants for five autoimmune diseases.

A deep-learning model called DeepSTARR quantitatively predicts enhancer activity on the basis of DNA sequence. The model learns relevant motifs and syntax rules, allowing for the design of synthetic enhancers with specific strengths.

The long isoform of DNMT3A is essential for mouse postnatal development and regulates bivalent genes in the brain, likely via a PRC1-mediated mechanism.

Genomic and transcriptomic analyses of chronic lymphoproliferative disorder of natural killer cells identifies somatic gain-of-function mutations in the chemokine gene CCL22 with cell-extrinsic effects. Mutations caused biased signaling downstream of the G-protein-coupled receptor for CCL22 and deregulated interactions with the hematopoietic microenvironment.

DNA methylation profiling of 565 meningiomas highlights three groups associated with distinct molecular, clinical and therapeutic features.

Imaging mass cytometry profiling of 693 breast tumors identified 10 recurrent tumor microenvironment spatial structures. These structures were enriched in different molecular subtypes and can be associated with genomic profiles and outcomes.

HOXB13 suppresses a lipogenic transcriptional program in prostate cancer (PCa) through HDAC3 recruitment to enhancers. Loss of HOXB13 leads to lipid accumulation in PCa cells, promoting cell motility in vitro and xenograft tumor metastasis in vivo.

Genome-wide epigenomic profiling of liver tissue from one surface and two independent cave populations of Astyanax mexicanus sheds light on regulatory changes underlying metabolic adaptations to the nutrient-deprived cave environment.

Whole-genome resequencing of 418 diverse rapeseed accessions and genome-wide association analyses for 56 agronomic traits provide insights into the genetic architecture and artificial selection or adaptation during modern rapeseed breeding.

Systematic phenotyping of 58,101 mutants of the model eukaryotic alga Chlamydomonas reinhardtii under 121 environmental and chemical stress conditions provides a large resource for characterizing gene function.

Genome assemblies for the SunUp transgenic papaya and its progenitor Sunset identify three transgene-insertions in SunUp. Resequencing of 86 papaya genomes highlights the impacts of breeding and geographic origin.

Orca is a sequence-based deep-learning algorithm that predicts 3D genome architecture from kilobase to whole-chromosome scale, including the impact of structural variants. In silico modeling identifies a putative sequence basis for chromatin compartment formation.