Volume 54 Issue 12, December 2022

It has been 25 years since the release of GATTACA, a film that tells the story of a credible near future in which society’s inequalities, formerly associated with race and class, have been replaced with new prejudices based on genetic determinism. Here we compare GATTACA’s fictional technologies with reality’s state of the art, assessing the legal protections afforded in today’s society against GATTACA’s dystopian future in which personal freedom and privacy rights are substantially curtailed by genomic innovations. We further discuss how GATTACA’s prescient forewarnings are still relevant today in light of the current trajectory of genomic science and technology.

The Qatar Genome Program was established to interrogate the genomics and genetics of populations in the Middle East. Improving precision medicine strategies and building long-term research capacity are both key aims of the initiative.

The evolutionary benefits of ongoing endogenous retrovirus (ERV) mobility in animals are largely unknown. A new paradigm suggests activation of the ERV family mdg4 at the fruitfly pupal stage may bolster adult antiviral defenses.

Previous genome-wide association studies of coronary artery disease (CAD) have discovered multiple susceptibility loci but have largely failed to uncover causal genes. A new study identifies hundreds of likely causal genes underlying the genetic risk for CAD.

K27M mutation of histone H3 has been identified as a driver event in diffuse midline glioma. Two studies used comprehensive multi-model single-cell genomic, epigenomic and chromatin structure analysis to characterize the cell of origin and find a distinct etiology of H3K27M between pontine and thalamic tumors, and show that pontine gliomas harbor more immature oligodendrocyte-precursor-like cells.

For plants, the decision to germinate is a gamble on their subsequent survival. Xu et al. have now discovered a mechanism that determines the choice between germination and dormancy by regulating the level of ABA.

Mutations in the sodium channel NALCN promote epithelial cell shedding and dissemination independent of oncogenic transformation. This observation suggests that metastasis may not uniformly represent the end stage of carcinogenesis but can occur before oncogenic transformation.

Few genetic alterations have been linked to metastasis, during which cancer cells acquire abnormal migratory behavior. A new study sheds light on how loss of NECTIN1 leads to melanoma dissemination after local depletion of IGF1.

We developed a CRISPR-based functional assay for genetic sequence variants found in human disease, probing their effects on cell proliferation, survival, motility and any physiological or pathological process measurable by fluorescence-activated cell sorting (FACS). The assay accurately assessed variant pathogenicity, drug responsiveness or resistance and mechanistic role in disease, in vitro and in vivo.

High-grade serous ovarian cancer, the most common form of the disease, is often fatal. This study investigated the genomic and immune characteristics of tumors from women who survived more than 10 years after their initial diagnosis, and compared them with short-term and moderate-term survivors.

Reanalysis of the immunotherapy-treated MSK-IMPACT cohort finds that chromosomal arm-level aneuploidy scores are an independent predictor of survival for patients with low tumor mutational burden.

Multistage gene burden analysis in exome sequencing data from 32,558 individuals identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease.

Cross-trait meta-analysis on 12 psychiatric disorders identifies the genetic overlap between pairs of disorders and highlights the challenges of cross-trait genetic research.

Genome-wide association analyses, functionally informed fine-mapping and complementary gene prioritization approaches identify new risk loci and candidate effector genes for CAD.

Multiancestry genome-wide association analyses in the Million Veteran Program and UK Biobank identify new risk loci for osteoarthritis. Drug repurposing analyses yield potential insights into the effects of antiepileptics on osteoarthritis pain.

The ion channel NALCN regulates cell shedding in mice and enhances metastasis in mouse models of cancer. Disseminated cells without oncogenic mutations form normal structures at secondary sites, suggesting that cell shedding is a physiological process that is hijacked during tumorigenesis.

Loss of NECTIN1 is a frequent event in human melanoma and is associated with metastasis. NECTIN1 depletion modulates a switch from cell–cell adhesion to cell–matrix adhesion in response to low levels of IGF1 signaling from the microenvironment.

A genomic and transcriptomic analysis identifies molecular features associated with long-term survival in ovarian cancer. Exceptional survival was heterogeneous across the cohort, suggesting that it is likely the function of multiple cell-intrinsic and microenvironmental factors working in combination.

Comprehensive genomic profiling of human H3K27M mutant diffuse midline gliomas, combining single-cell RNA sequencing and ATAC sequencing with bulk ChIP sequencing and other data, proposes distinct oligodendrocyte populations as potential cells of origin.

Single-cell RNA-seq and ATAC-seq, combined with spatial transcriptomics, identify age- and location-related cellular dynamics of diffuse midline gliomas, such as variable oligodendrocyte precursor-like tumor stem cell populations and increased mesenchymal states with age.

Co-deletion of all proteins with a functional methyl-CpG-binding domain does not impact genes or repeats silenced by DNA methylation. Analysis of chromatin accessibility and sequence motifs identifies transcription factors that appear sensitive to DNA methylation.

Live-cell imaging shows that interactions within topologically associating domains are transient and frequent throughout the cell cycle. Convergent CTCF sites regulate the frequency and duration of interactions, which last a few minutes on average.

Micro-C and nascent transcript profiling in mouse embryonic stem cells shows that enhancer–promoter interactions are robust to acute depletion of CTCF, cohesin, WAPL or YY1. Live-cell, single-molecule imaging shows that cohesin depletion reduces transcription factor binding to chromatin.

Expression of mdg4 retrotransposons during Drosophila metamorphosis activates the antiviral NF-κB factor Relish. Silencing of mdg4 or Relish at the pupal stage leads to an inability to clear exogenous viruses in adulthood.

Prrx1-expressing can act as stem cells for bone, white adipose tissue and dermis in adult mice. These cells have a key role in tissue homeostasis and repair and are regulated by Wnt signaling.

Pan-genome and pan-3D genome analyses of the Gossypium genus reveal evolutionary relationships among transposon-driven genome expansion and chromatin topology innovation and regulatory variations for cotton fiber development.

SD6, which encodes a bHLH transcription factor, along with another bHLH factor ICE2, antagonistically controls rice seed dormancy by regulating ABA catabolism and biosynthesis genes in a temperature-dependent manner.

CRISPR-Select is a quantitative assay for the functional impact of genetic variants, including pathogenicity, drug response, oncogenicity, cell motility and other cell states.