Volume 52 Issue 1, January 2020

Recent advances in Hi-C, single-cell imaging and functional genetic studies warrant discussion on the functional relevance of topologically associating domains (TADs) and other classes of chromatin domains.

Ancestral and geographical issues underlie the need to develop Africa-specific guidelines for the return of genomics research results in Africa. In this Commentary, we outline the challenges that will inform policies and practices in the future.

The 11^th International Conference on Rare Diseases and Orphan Drugs (ICORD), South Africa, included the Africa-Rare initiative launch and facilitated multi-stakeholder engagement in the challenges facing, and opportunities for, Africans living with rare diseases. The following ICORD Global Call to Action, developed in collaboration with the International Rare Diseases Research Consortium, synthesizes the outcomes of the deliberations and emphasizes the international collaborative efforts required to address the global effects of rare diseases on public health.

RNA:DNA hybrids that form across genomes control a wide range of biological processes. A new study shows that N⁶-methyladenosine (m⁶A) modification on the RNA moieties regulates the formation and genome integrity of these hybrids. This finding opens a new avenue of research on how RNA modifications (the ‘epitranscriptome’) can help control genome maintenance.

Combined genomic and transcriptomic approaches identify the landscape of extrachromosomal circular DNA in neuroblastoma and reveal that extrachromosomal circular DNA is a major source of somatic rearrangements.

GeVIR is a continuous gene-level metric that uses variant distribution patterns to prioritize both dominant and recessive Mendelian disease genes. GeVIR outperforms missense constraint metrics and complements loss-of-function constraint metrics.

Mutations in ADAMTS19 lead to progressive heart valve disease in humans. Analysis of mice lacking Adamts19 highlights the role of a Wnt–Adamts19–Klf2 axis in proper valve function.

N⁶-methyladenosine (m⁶A) is prevalent at RNA:DNA hybrids in human pluripotent stem cells. The m⁶A reader YTHDF2 interacts with R-loop-enriched loci in dividing cells, and YTHDF2 loss leads to increased R-loop levels and accumulation of γH2AX.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Whole-genome sequencing and phylogenetic analysis of nearly 400 esophageal adenocarcinoma samples suggest a model of rapid subclone spreading from the primary tumor to multiple metastatic sites, which the authors term ‘clonal diaspora’.

pgFARM (paired guide RNAs for alternative exon removal) is a CRISPR–Cas9-based approach to manipulate alternative splicing and identify functional roles for individual exons, including poison exons with essential and tumor-suppressor roles.

Genome-wide maps of chromatin dynamics during mouse gastrulation highlight a unique bivalent signature at developmental genes in E6.5 epiblast cells. KMT2B is essential for bivalent H3K4me3 at E6.5.

Analysis of a near-chromosomal genome assembly and transcriptome profiling of the Indian cobra identifies genes expressed in the venom glands. These data should help develop a new antivenom.

Resequencing and genome-wide association analysis of 683 common bean accessions across different latitudes identifies 505 loci associated with yield components, of which seed size, flowering and harvest maturity traits are stable across environments.

A method to cluster genetic risk profiles applied to 3,025 loci across 19,155 disease codes from over 300,000 individuals in the UK Biobank identifies 339 distinct disease association profiles and links clusters to biological pathways.