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The authors review genetic studies of sensorineural hearing impairment (SNHI) and their resulting insights into the molecular mechanisms underlying auditory system function. They also discuss preclinical studies of inner-ear gene therapy and key translational opportunities and challenges for treating monogenic forms of SNHI and associated balance disorders.
Recent systems biology and single-cell approaches have revealed the impact of the microenvironment, lineage specification and cell identity, and the genome on epithelial–mesenchymal plasticity (EMP). In addition, cell memory (hysteresis) and cellular noise can drive stochastic transitions between cell states. The authors review these forces and the regulatory mechanisms that stabilize EMP states or facilitate epithelial–mesenchymal transitions (EMTs).
Wagner et al. report an organism-wide map of non-coding RNA expression in ageing and rejuvenated mice, identifying a set of broadly deregulated microRNAs that may act as systemic regulators of ageing.
Hook and Timp describe increasingly flexible ways in which single-molecule sequencing technologies are being used to analyse genomes. Examples include targeted genome sequencing, analysis of chromatin state and protein–DNA interactions, and sequencing of short reads.
In this Review, Gaulton et al. discuss how single-cell epigenomic methods generate cell type-, subtype- and state-resolved maps of candidate cis-regulatory elements in heterogeneous human tissues that can help to interpret the genetic basis of common traits and diseases.
Differences in facial morphology distinguish vertebrates. Here, Selleri and Rijli discuss advances in multi-omics and single-cell technologies linking genes, transcriptional networks and epigenetic landscapes to the establishment of facial patterning and its variation, with an emphasis on normal and abnormal craniofacial morphogenesis.
In this Review, the authors describe the emerging field of single-cell genetics, which lies at the intersection of single-cell genomics and human genetics. They review the first single-cell expression quantitative trait loci studies, which combine single-cell information with genotype data at the population scale and thereby link genetic variation to the cellular processes underpinning key aspects of human biology and disease.
Arutyunyan et al. describe a spatially resolved, single-cell multi-omics map of the entire maternal–fetal interface in the first trimester of human pregnancy.
Mutations that affect primary cilia cause ciliopathies with variable severity and expressivity. The diversity of cilia across cell types, tissues and developmental stages enables their function as versatile signalling hubs but may underlie the disconnect between genotype and phenotype. This Review examines the structural and functional diversity of primary cilia, their dynamic regulation in different cellular and developmental contexts and their disruption in disease.
In this Journal Club, Loic Yengo discusses a study by Tenesa et al., who used height as a model complex trait to estimate the degree to which height similarity between spouses is caused by mate choice.
Sophie von der Heyden highlights a paper by Barber et al. that examined variations in the genetic structuring of populations of the mantis shrimp Haptosquilla pulchella, furthering our understanding of the evolutionary dynamics of marine species.
A new study in Science reports the mechanism through which TDP-43 enables correct processing of STMN2 mRNA, and proposes strategies to restore neuronal Stathmin-2 synthesis in TDP-43 proteinopathies.
Variant calling is the process of identifying genetic variants, which is important for characterizing population genetic diversity and for identifying disease-associated variants in clinical sequencing projects. In this Review, the authors discuss the state-of-the-art in variant calling, focusing on challenging types of genetic variants, advances in both sequencing technologies and computational pipelines, and benchmarking strategies to assess the robustness of variant-calling strategies.
A paper in Cell introduces the EN-TEx resource, a detailed catalogue of allele-specific activity that can be used to develop deep learning models that analyse the biological impact of genetic variants.
In this Review, the authors discuss our growing knowledge of the underlying genetics of amyotrophic lateral sclerosis (ALS; also known as motor neuron disease). They discuss how this information provides insight into causal disease mechanisms and translational opportunities for developing clinical therapeutics.
