Trends in Genetics
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New articles

Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

September 19, 2022


Insights from multi-omics integration in complex disease primary tissues

  • Peter Kreitmaier,
  • Georgia Katsoula,
  • Eleftheria Zeggini
First published:September 19, 2022
Open Access
Genome-wide association studies (GWAS) have provided insights into the genetic basis of complex diseases. In the next step, integrative multi-omics approaches can characterize molecular profiles in relevant primary tissues to reveal the mechanisms that underlie disease development. Here, we highlight recent progress in four examples of complex diseases generated by integrative studies: type 2 diabetes (T2D), osteoarthritis, Alzheimer’s disease (AD), and systemic lupus erythematosus (SLE). High-resolution methodologies such as single-cell and spatial omics techniques will become even more important in the future.

Emerging functions of mitochondria-encoded noncoding RNAs

  • Bingbing Ren,
  • Min-Xin Guan,
  • Tianhua Zhou,
  • Xiujun Cai,
  • Ge Shan
First published:September 19, 2022
Open Access
Mitochondria, organelles that harbor their own circular genomes, are critical for energy production and homeostasis maintenance in eukaryotic cells. Recent studies discovered hundreds of mitochondria-encoded noncoding RNAs (mt-ncRNAs), including novel subtypes of mitochondria-encoded circular RNAs (mecciRNAs) and mitochondria-encoded double-stranded RNAs (mt-dsRNAs). Here, we discuss the emerging field of mt-ncRNAs by reviewing their expression patterns, biogenesis, metabolism, regulatory roles, and functional mechanisms.

September 1, 2022


The potential role of the mobile and non-coding genomes in adaptive response

  • Alice M. Godden,
  • Simone Immler
First published:September 01, 2022
Open Access
The tightly regulated feedback loops linking small RNAs (sRNAs) and transposable elements (TEs) offer the opportunity for an adaptive response to changing environments at the molecular level. Environmentally induced changes in TE and sRNA profiles may affect expression of coding genes and trigger an organismic and transgenerational response. Understanding this link may provide a mechanistic explanation for how species can adapt to changing climates and may offer novel molecular targets for biomedical and agricultural applications.

August 31, 2022


Chromoanagenesis in plants: triggers, mechanisms, and potential impact

  • Weier Guo,
  • Luca Comai,
  • Isabelle M. Henry
First published:August 31, 2022
Chromoanagenesis is a single catastrophic event that involves, in most cases, localized chromosomal shattering and reorganization, resulting in a dramatically restructured chromosome. First discovered in cancer cells, it has since been observed in various other systems, including plants. In this review, we discuss the origin, characteristics, and potential mechanisms underlying chromoanagenesis in plants. We report that multiple processes, including mutagenesis and genetic engineering, can trigger chromoanagenesis via a variety of mechanisms such as micronucleation, breakage–fusion–bridge (BFB) cycles, or chain-like translocations.

August 26, 2022


Mitochondrial genome engineering coming-of-age

(Trends in Genetics, 38: 8, 869–880, 2022)

  • Jose Domingo Barrera-Paez,
  • Carlos T. Moraes
First published:August 26, 2022
Error in the acknowledgments.

August 20, 2022


Earth Biogenome Project: present status and future plans

(Trends in Genetics 38:8 p: 811–820, 2022)

  • Pushpendra Kumar Gupta
First published:August 20, 2022
The following corrections are needed in the text appearing on pages 811 and 815.

August 6, 2022

Feature Review

Progress and opportunities through use of genomics in animal production

  • Huw E. Jones,
  • Philippe B. Wilson
First published:August 06, 2022
Open Access
The rearing of farmed animals is a vital component of global food production systems, but its impact on the environment, human health, animal welfare, and biodiversity is being increasingly challenged. Developments in genetic and genomic technologies have had a key role in improving the productivity of farmed animals for decades. Advances in genome sequencing, annotation, and editing offer a means not only to continue that trend, but also, when combined with advanced data collection, analytics, cloud computing, appropriate infrastructure, and regulation, to take precision livestock farming (PLF) and conservation to an advanced level.

August 4, 2022


Passing down maternal dietary memories through lncRNAs

  • Xin Yi Koh,
  • Jun Wei Pek
First published:August 04, 2022
Parental diet is known to influence the offspring in an intergenerational manner, and this has been implicated in species adaptation and general health. Recent studies highlight the role of maternal long noncoding RNAs (lncRNAs) in serving as one of the 'memories' of maternal diet in regulating offspring development and predisposition to metabolic disease.

Transperons: RNA operons as effectors of coordinated gene expression in eukaryotes

  • Rohini R. Nair,
  • Emese Pataki,
  • Jeffrey E. Gerst
First published:August 04, 2022
Coordinated gene expression allows spatiotemporal control of cellular processes and is achieved by the cotranscription/translation of functionally related genes/proteins. Prokaryotes evolved polycistronic messages (operons) to confer expression from a single promoter to efficiently cotranslate proteins functioning on the same pathway. Yet, despite having far greater diversity (e.g., gene number, distribution, modes of expression), eukaryotic cells employ individual promoters and monocistronic messages.

Ionizing radiation damage and repair from 3D-genomic perspective

  • Yang Zheng,
  • Hao Li,
  • Xiaochen Bo,
  • Hebing Chen
First published:August 04, 2022
Open Access
Ionizing radiation (IR)-induced DNA damage and repair are complex and occur at hierarchical chromatin structures; radiobiology needs to be studied from a 3D-genomic perspective. Differences in IR damage and repair throughout the 3D genome may help to explain differences in radiosensitivity.

Effective therapies for sickle cell disease: are we there yet?

  • Merlin Crossley,
  • Georgios E. Christakopoulos,
  • Mitchell J. Weiss
First published:August 04, 2022
Sickle cell disease (SCD) is a common genetic blood disorder associated with acute and chronic pain, progressive multiorgan damage, and early mortality. Recent advances in technologies to manipulate the human genome, a century of research and the development of techniques enabling the isolation, efficient genetic modification, and reimplantation of autologous patient hematopoietic stem cells (HSCs), mean that curing most patients with SCD could soon be a reality in wealthy countries. In parallel, ongoing research is pursuing more facile treatments, such as in-vivo-delivered genetic therapies and new drugs that can eventually be administered in low- and middle-income countries where most SCD patients reside.

Phenotype-aware prioritisation of rare Mendelian disease variants

  • Catherine Kelly,
  • Anita Szabo,
  • Nikolas Pontikos,
  • Gavin Arno,
  • Peter N. Robinson,
  • Jules O.B. Jacobsen,
  • Damian Smedley,
  • Valentina Cipriani
First published:August 04, 2022
Open Access
A molecular diagnosis from the analysis of sequencing data in rare Mendelian diseases has a huge impact on the management of patients and their families. Numerous patient phenotype-aware variant prioritisation (VP) tools have been developed to help automate this process, and shorten the diagnostic odyssey, but performance statistics on real patient data are limited. Here we identify, assess, and compare the performance of all up-to-date, freely available, and programmatically accessible tools using a whole-exome, retinal disease dataset from 134 individuals with a molecular diagnosis.

July 16, 2022

Feature Review

DNA base editing in nuclear and organellar genomes

  • Junjie Tan,
  • Joachim Forner,
  • Daniel Karcher,
  • Ralph Bock
First published:July 16, 2022
Open Access
Genome editing continues to revolutionize biological research. Due to its simplicity and flexibility, CRISPR/Cas-based editing has become the preferred technology in most systems. Cas nucleases tolerate fusion to large protein domains, thus allowing combination of their DNA recognition properties with new enzymatic activities. Fusion to nucleoside deaminase or reverse transcriptase domains has produced base editors and prime editors that, instead of generating double-strand breaks in the target sequence, induce site-specific alterations of single (or a few adjacent) nucleotides.

July 9, 2022

Genome of the Month

Solanum tuberosum (potato)

  • Ling Kui,
  • Aasim Majeed,
  • Sulaiman Ahmed,
  • Muhammad Saad Shoaib Khan,
  • Faisal Islam,
  • Jian Chen,
  • Yang Dong
First published:July 09, 2022
The potato was domesticated in the Andes around 8000–10 000 years ago but has dispersed globally since then. Since potatoes are mainly propagated clonally, the deleterious and dysfunctional alleles remain unpurged during meiosis. Most commonly cultivated and consumed tetraploid cultivars are highly heterozygous, possess rampant structural variations, and a high degree of intragenome heterogeneity, complicating the genome assembly process.

Complex genomic rearrangements: an underestimated cause of rare diseases

  • Jakob Schuy,
  • Christopher M. Grochowski,
  • Claudia M.B. Carvalho,
  • Anna Lindstrand
First published:July 09, 2022
Open Access
Complex genomic rearrangements (CGRs) are known contributors to disease but are often missed during routine genetic screening. Identifying CGRs requires (i) identifying copy number variants (CNVs) concurrently with inversions, (ii) phasing multiple breakpoint junctions in cis, as well as (iii) detecting and resolving structural variants (SVs) within repeats. We demonstrate how combining cytogenetics and new sequencing methodologies is being successfully applied to gain insights into the genomic architecture of CGRs.

July 8, 2022


Synthesizing genome regulation data with vote-counting

  • Martin Fischer,
  • Steve Hoffmann
First published:July 08, 2022
Open Access
The increasing availability of high-throughput datasets allows amalgamating research information across a large body of genome regulation studies. Given the recent success of meta-analyses on transcriptional regulators, epigenetic marks, and enhancer:gene associations, we expect that such surveys will continue to provide novel and reproducible insights. However, meta-analyses are severely hampered by the diversity of available data, concurring protocols, an eclectic amount of bioinformatics tools, and myriads of conceivable parameter combinations.

Chromosome-scale haplotype-resolved pangenomics

  • Shilpa Garg,
  • Renzo Balboa,
  • Josiah Kuja
First published:July 08, 2022
Complete pangenomics is crucial for understanding genetic diversity and evolution across the tree of life. Chromosome-scale, haplotype-resolved pangenomics allows complex structural variations, long-range interactions, and associated functions to be discerned in species populations. We explore the need for high-resolution pangenomes, discuss computational strategies for their development, and describe applications in biodiversity and human health.

July 7, 2022


New mechanism of chromatin compartmentalization by BRD2

  • Yubao Cheng,
  • Siyuan Wang
First published:July 07, 2022
Open Access
The molecular mechanism underlying 3D genome compartmentalization remains a mystery. Xie et al. found that the bromodomain and extraterminal (BET) family scaffold protein BRD2 promotes the compartmentalization of the accessible chromatin domains after cohesin loss. An antagonistic interplay between loop extrusion and compartmentalization modulates chromatin folding.

Unusual suspects in hereditary melanoma: POT1, POLE, BAP1

  • Ellie J. Maas,
  • Brigid Betz-Stablein,
  • Lauren G. Aoude,
  • H. Peter Soyer,
  • Aideen M. McInerney-Leo
First published:July 07, 2022
Systematic literature searches on POT1/POLE/BAP1 found that limited skin phenotypic characteristics have been documented in mutation carriers; 248 variants were annotated, and high-cluster variant regions associated with cutaneous melanoma were found in all three genes. Genotype–phenotype correlations can be used to identify patient disease predisposition based on mutation position and cluster regions.

July 6, 2022


Dissecting super-enhancer heterogeneity: time to re-examine cancer subtypes?

  • Tan Wu,
  • Hao Huang,
  • Xin Wang
First published:July 06, 2022
Open Access
The heterogeneity of transcriptional regulations by super-enhancers (SEs) is poorly understood in human cancers. Herein, we summarize a bioinformatics workflow for genome-wide SE profiling and identification of subtype-specific SEs and regulatory networks. Dissecting SE heterogeneity provides new insights into cancer biology and alternative therapeutic strategies for cancer precision medicine.

July 2, 2022


Resolving m6A epitranscriptome with stoichiometry

  • Ki-Jun Yoon,
  • Yoon Ki Kim
First published:July 02, 2022
A recent study by Hu et al. describes N6-methyladenosine (m6A)-selective allyl chemical labeling and sequencing (m6A-SAC-seq), which allows for quantitative, stoichiometric, and positional analyses of m6A at single-nucleotide resolution across the whole transcriptome level. Information on the m6A stoichiometry will provide additional layers of gene regulatory pathways mediated by m6A modification during diverse molecular, cellular, and physiological events.

June 27, 2022


The road not taken: host genetics in shaping intergenerational microbiomes

  • Shuqin Zeng,
  • Shaopu Wang,
  • R. Paul Ross,
  • Catherine Stanton
First published:June 27, 2022
The early-life gut microbiome is linked to human phenotypes as an imbalanced microbiome of this period is implicated in diseases throughout life. Several determinants of early-life gut microbiome are explored, however, mechanisms of acquisition, colonization, and stability of early-life gut microbiome and their interindividual variability remain elusive. Host genetics play a vital role to shape the gut microbiome and interact with it to modulate individual phenotypes in human studies and animal models.

June 20, 2022


Optogenetics for transcriptional programming and genetic engineering

  • Tien-Hung Lan,
  • Lian He,
  • Yun Huang,
  • Yubin Zhou
First published:June 20, 2022
Open Access
Optogenetics combines genetics and biophotonics to enable noninvasive control of biological processes with high spatiotemporal precision. When engineered into protein machineries that govern the cellular information flow as depicted in the central dogma, multiple genetically encoded non-opsin photosensory modules have been harnessed to modulate gene transcription, DNA or RNA modifications, DNA recombination, and genome engineering by utilizing photons emitting in the wide range of 200–1000 nm. We present herein generally applicable modular strategies for optogenetic engineering and highlight latest advances in the broad applications of opsin-free optogenetics to program transcriptional outputs and precisely manipulate the mammalian genome, epigenome, and epitranscriptome.

June 18, 2022


lncRNAs in fertility: redefining the gene expression paradigm?

  • Yonatan B. Tzur
First published:June 18, 2022
Comparative transcriptome approaches assume that highly or dynamically expressed genes are important. This has led to the identification of many genes critical for cellular activity and organism development. However, while testes express the highest levels of long noncoding RNAs (lncRNAs), there is scarcely any evidence for lncRNAs with significant roles in fertility. This was explained by changes in chromatin structure during spermatogenesis that lead to ‘promiscuous transcription’ with no functional roles for the transcripts.

May 28, 2022


Slippy-Sloppy translation: a tale of programmed and induced-ribosomal frameshifting

  • Julien Champagne,
  • Kelly Mordente,
  • Remco Nagel,
  • Reuven Agami
First published:May 28, 2022
Programmed ribosomal frameshifting (PRF) is a key mechanism that viruses use to generate essential proteins for replication, and as a means of regulating gene expression. PRF generally involves recoding signals or frameshift stimulators to elevate the occurrence of frameshifting at shift-prone ‘slippery’ sequences. Given its essential role in viral replication, targeting PRF was envisioned as an attractive tool to block viral infection. However, in contrast to controlled-PRF mechanisms, recent studies have shown that ribosomes of many human cancer cell types are prone to frameshifting upon amino acid shortage; thus, these cells are deemed to be sloppy.

Gene product diversity: adaptive or not?

  • Jianzhi Zhang,
  • Chuan Xu
First published:May 28, 2022
One gene does not equal one RNA or protein. The genomic revolution has revealed numerous different RNA and protein molecules that can be produced from one gene, such as circular RNAs generated by back-splicing, proteins with residues mismatching the genomic encoding because of RNA editing, and proteins extended in the C terminus via stop codon readthrough in translation. Are these diverse products results of exquisite gene regulations or imprecise biological processes? While there are cases where the gene product diversity appears beneficial, genome-scale patterns suggest that much of this diversity arises from nonadaptive, molecular errors.

May 25, 2022


Without mechanisms, theories and models in insect epigenetics remain a black box

  • Ryszard Maleszka,
  • Robert Kucharski
First published:May 25, 2022
Insect epigenetics must confront the remarkable diversity of epigenomic systems in various lineages and use mechanistic approaches to move beyond vague functional explanations based on predictions and inferences. To accelerate progress, what is required now is a convergence of genomic data with biochemical and single-cell-type analyses in selected species representing contrasting evolutionary solutions in epigenetics.

May 14, 2022


A new Down syndrome rat model races forward

  • Randall J. Roper,
  • Charles R. Goodlett
First published:May 14, 2022
Animal models of Down syndrome (DS) provide an essential resource for understanding genetic, cellular, and molecular contributions to traits associated with trisomy 21 (Ts21). Recent genetic enhancements in the development of DS models, including the new TcHSA21rat model ( Kazuki et al.), have potential to transform our understanding of and potential therapies for Ts21.