Volume 50 Issue 9, September 2018

A new study uses multicolor live imaging to simultaneously visualize enhancer–promoter interaction and transcription in Drosophila embryos.

Two new studies show that a plant-specific complex composed of EBS, or its homolog SHL, and EMF1 acts as a chromatin reader within the Polycomb pathway and effects gene repression. Two domains of EBS and SHL bind distinct chromatin modifications that are associated with active and repressed chromatin.

A new study uncovers novel copy number signatures in ovarian cancer genomes. This work sheds light on mutational processes driving ovarian cancer, reveals the distribution of copy number features across the patient population and identifies new genomic properties related to treatment response.

Individual genome-wide polygenic risk scores (GPSs) for assessing disease susceptibility have been shown to yield both reliable and clinically meaningful results. However, certain impediments and outdated ways of thinking about health maintenance must be overcome before GPSs are adopted in routine care streams.

This proposal calls for the initiation of national population-screening programs to identify carriers of cancer gene mutations for long-term, large-scale analysis of longitudinal clinical data to aid in prevention and early detection of disease.

Genome-wide polygenic risk scores derived from GWAS data for five common diseases can identify subgroups of the population with risk approaching or exceeding that of a monogenic mutation.

This large, multi-ethnic genome-wide association study identifies 97 loci significantly associated with atrial fibrillation. These loci are enriched for genes involved in cardiac development, electrophysiology, structure and contractile function.

Large-scale association analyses identify 142 independent risk variants for atrial fibrillation. Pathway and functional enrichment analyses suggest that many of the putative risk genes act via cardiac structural remodeling.

This study identifies a set of critical dependency genes in MYCN-amplified neuroblastoma that make up the oncogenic transcriptional regulatory circuitry underlying cell state and tumor survival.

EBS, which prevents premature flowering in Arabidopsis, is shown to bind H3K27me3 and H3K4me3 via different domains. Disruption of either EBS–H3K27me3 or EBS–H3K4me3 interaction induces early floral transition.

Two BAH-domain-containing proteins (SHL and EBS) form a complex with EMF1, reading and effecting the H3K27me3 mark in Arabidopsis. The BAH-EMF1c complex thus shows PRC1-like functions in higher plants.

The authors identify copy number signatures from shallow whole-genome sequencing of high-grade serous ovarian cancer (HGSOC) cases. HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in genomic aberration.

Analysis of sequencing data from 249 cancer patients with clinically annotated outcomes to immune checkpoint therapy identifies correlates of treatment response. The results highlight complexity in identifying events that generate an immunoresponsive tumor environment.

Sequencing and de novo assembly of the maize W22 reference genome enable accurate placement of Mutator (Mu) and Dissociation (Ds) transposable element insertions, providing a foundation for maize functional genomics and transposon biology.

The de novo genome assembly of maize line Mo17 and comparative analysis with other sequenced maize lines show extensive gene-order variations. This study provides insights into maize evolution and has implications for improving maize hybrid lines.

The authors use genome editing and live imaging to visualize physical enhancer–promoter interaction and transcription at the single-cell level in Drosophila embryos. They show that sustained proximity of an enhancer to its target is required for transcription.

Relatedness disequilibrium regression is a new method for estimating heritability that removes environmental bias by taking advantage of variation in relatedness due to random Mendelian segregation.

ASMC is a new method to estimate coalescence times using SNP array or sequencing data. When applied to data from the UK Biobank or Genome of the Netherlands, ASMC detects signals of recent positive selection and background selection.

Analysis of summary statistics from 32 GWAS datasets using a new likelihood-based approach evaluates polygenicity across different traits. Effect-size distributions predict the sample sizes needed to explain the SNP-based heritability of traits.

Analysis of GTEx, cancer and autism data sets shows that cis-regulatory variation can modify the penetrance of coding variants. Deleterious coding variants on regulatory haplotypes resulting in high expression are enriched in disease cohorts and selected against in general populations.

SAIGE (Scalable and Accurate Implementation of GEneralized mixed model) is a generalized mixed model association test that can efficiently analyze large data sets while controlling for unbalanced case-control ratios and sample relatedness, as shown by applying SAIGE to the UK Biobank data for > 1,400 binary phenotypes.