Sep 2025

• Advisory Board and Contents

Science & Society

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  Generative AI: a partner for genetic counseling?

  • Kenny Wong,
  • Vivian Pan,
  • Colleen Caleshu

  Generative artificial intelligence (AI)'s arrival in genetic counseling presents both opportunities and challenges. While offering the potential to ease burdens (e.g., by automating routine screening and summarizing patient histories) and expand access (e.g., through AI-driven preliminary education and interactive counseling), its integration demands careful evaluation, ethical design focusing on equity and privacy, and robust collaboration to ensure increased access and improved patient outcomes.

Spotlights

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  Unraveling immunity: insights from biobank-scale data

  • Ashley Richardson,
  • Kailash BP,
  • Chad H. Hogan

  The scale and granularity of biobanks are reshaping the future of immunogenetics, enabling breakthroughs at a pace never before possible. Here, we highlight two recent preprints that apply novel statistical methods to biobank data to understand how inherited variants shape immune traits and disease risk.
• 

  Sleeping less with a SIK3 mutation

  • Xin Yin,
  • Qinghua Liu

  Natural short sleepers (NSS) need only 4–6 h of sleep per night to function efficiently without negative health effects. Chen et al. recently found an NSS mutation in the salt-induced kinase 3 (SIK3) gene, shedding new light on the genetic basis of human sleep regulation.

Feature Review

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  Epigenetic effects of paternal environmental exposures and experiences on offspring phenotypes

  • Huan Liao,
  • Da Lu,
  • Sonali N. Reisinger,
  • Mehrshad Rashidi Mehrabadi,
  • Carolina Gubert,
  • Anthony J. Hannan

  Recent decades have revealed increasing evidence for epigenetic inheritance through paternal environmental exposures and experiences, affecting offspring health outcomes across diverse species. Key epigenetic mediators in sperm may include DNA methylation, chromatin modifications, as well as small and long non-coding (nc)RNAs. Identified environmental influences extend beyond lifestyle factors (e.g., exercise, diet, alcohol, and nicotine use) to include stress, infections, pollutants, and other toxins. Evidence from humans, rodents, and other species suggests that various paternal exposures before conception substantially shape the phenotypes in offspring, via developmental modulation, including changes to brain and behavior, metabolism, endocrinology, and physiology. These findings raise concerns regarding human epigenetic inheritance, because the relevant environmental exposures have changed significantly in recent decades, potentially increasing the risk of future generations for various disorders (‘transgenerational epigenopathy’). Here, we integrate evidence for paternal environmental exposures affecting offspring phenotypes, and associated epigenetic mechanisms, critically discussing potential implications for medicine and other scientific fields.

Reviews

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  The rare-to-common disease journey: a winding road to new therapies

  • Laura Reinholdt,
  • Elissa Chesler,
  • Martin Pera,
  • Nadia Rosenthal

  Open Access

  The study of genetic variants that cause rare diseases has been a central strategy of genetic research for the last century, but the contribution of rare variants to the multifactorial inheritance of common diseases has only recently emerged as an avenue to accelerate functional mapping of the human genome. This perspective defines rare and common diseases, surveys prospects for integrating their study to decipher pathogenic mechanisms, and cites current clinical hurdles of disease translation. We discuss the premise that research into rare disease etiology can inform our understanding of common illnesses and vice versa, identify impediments to progress in translating rare disease findings into common disease treatments, and offer suggestions for realizing the benefits of global health research in the discovery of rare disease variants.
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  Spatial omics enters the microscopic realm: opportunities and challenges

  • Yichen Si,
  • Joo Sang Lee,
  • Goo Jun,
  • Hyun Min Kang,
  • Jun Hee Lee

  Spatial transcriptomics (ST) enables systematic profiling of whole-transcriptome gene expression in tissues while preserving spatial context. Recent advances in sequencing- and imaging-based ST technologies have ushered in the era of microscopic-resolution ST (μST), allowing transcriptome mapping at cellular and even subcellular scales with unprecedented precision. Despite these advances, μST faces substantial challenges, including sparse transcript discovery per submicron (or micron)-sized spatial units and data fragmentation across platforms, hindering integration and analysis. There is also a growing demand for scalable, segmentation-free, and universally applicable analysis methods, as well as strategies for 3D mapping, multi-omics integration, and artificial intelligence (AI)-driven spatial analysis. In this review, we highlight recent breakthroughs, outline key challenges, and discuss emerging experimental and computational solutions shaping the future of μST.
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  Optimizing homology-directed repair for gene editing: the potential of single-stranded DNA donors

  • Ying-Ying Jin,
  • Peng Zhang,
  • De-Pei Liu

  CRISPR (clustered regularly interspaced short palindromic repeat) system-based precise genome editing remarkably impacts both scientific investigation and therapeutic practices. Among various techniques, DNA donor–mediated homology-directed repair (HDR) represents a promising method for precise gene editing. Although efficiency constraints have previously limited HDR, recent advancements have significantly enhanced its effectiveness. Therefore, it is essential to highlight the progress made in this field and to reassess the potential of the HDR approach. In this review, we explore the fundamental principles of HDR-dependent gene editing and evaluate current strategies to enhance HDR efficiency, with particular emphasis on single-stranded DNA (ssDNA) donor-mediated HDR. Finally, we discuss the prospects of high-efficiency ssDNA donor-mediated precise gene editing in laboratory research and clinical therapies.
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  Selection on the epigenome: small RNA inheritance in animal evolution

  • Isaac Harris,
  • Simone Immler,
  • Tracey Chapman,
  • Alexei A. Maklakov

  Open Access

  The inheritance of small RNAs (sRNAs) is taxonomically widespread. Changing environments alter the production and presence of sRNAs in the germline, and this can in theory either increase offspring phenotypic variance as an evolutionary bet-hedging strategy or elicit predictive and adaptive phenotypic responses that increase offspring fitness. Nevertheless, the putative role of sRNA inheritance systems in adaptive evolution is still debated and it is currently unclear how selection acts on sRNAs. We outline two adaptive sRNA inheritance strategies – specialist and generalist – and discuss non-adaptive alternatives and the evolutionary implications of different strategies. Our review suggests that the role of natural selection in sRNA inheritance has been significantly overlooked, potentially leading to misinterpretations of the causal agents and the evolutionary implications of sRNA inheritance.
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  Epigenetic perspectives on wheat speciation, adaptation, and development

  • Xuemei Liu,
  • Dongzhi Wang,
  • Zhaoheng Zhang,
  • Xuelei Lin,
  • Jun Xiao

  Bread wheat (Triticum aestivum) has undergone a complex evolutionary history shaped by polyploidization, domestication, and adaptation. Recent advances in multiomics approaches have shed light on the role of epigenetic mechanisms, including DNA methylation, histone modification, chromatin accessibility, and noncoding RNAs, in regulating gene expression throughout these processes. Epigenomic reprogramming contributes to genome stability and subgenome differentiation and modulates key agronomic traits by influencing flowering time, environmental responses, and developmental programs. This review synthesizes current insights into epigenetic regulation of wheat speciation, adaptation, and development, highlighting their potential applications in crop improvement. A deeper understanding of these mechanisms will facilitate targeted breeding strategies leveraging epigenetic variations to enhance wheat resilience and productivity in the face of changing environments.

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