Deciphering the role of structural variation in human evolution: a functional perspective

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 88, P. 102240 - 102240

Published: Aug. 8, 2024

Advances in sequencing technologies have enabled the comparison of high-quality genomes diverse primate species, revealing vast amounts divergence due to structural variation. Given their large size, variants (SVs) can simultaneously alter function and regulation multiple genes. Studies estimate that collectively more than 3.5% genome is divergent humans versus other great apes, impacting thousands Functional genomics gene-editing tools various model systems recently emerged as an exciting frontier - investigating wide-ranging impacts SVs on molecular, cellular, systems-level phenotypes. This review examines existing research identifies future directions broaden our understanding functional roles phenotypic innovations diversity uniquely human features, ranging from cognition metabolic adaptations.

Language: Английский

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Protocol to process fresh human cerebral cortex biopsies for patch-clamp recording and immunostaining

STAR Protocols, Journal Year: 2024, Volume and Issue: 5(4), P. 103313 - 103313

Published: Sept. 17, 2024

Language: Английский

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Human-specific genetic modifiers of cortical architecture and function

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 88, P. 102241 - 102241

Published: Aug. 6, 2024

Language: Английский

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Gene expansions contributing to human brain evolution

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Genomic drivers of human-specific neurological traits remain largely undiscovered. Duplicated genes expanded uniquely in the human lineage likely contributed to brain evolution, including increased complexity synaptic connections between neurons and dramatic expansion neocortex. Discovering duplicate is challenging because similarity paralogs makes them prone sequence-assembly errors. To mitigate this issue, we analyzed a complete telomere-to-telomere genome sequence (T2T-CHM13) identified 213 duplicated gene families containing (>98% identity). Positing that important universal features should exist with at least one copy all modern humans exhibit expression brain, narrowed on 362 across thousands ancestrally diverse genomes present transcriptomes. Of these, 38 co-express modules enriched for autism-associated potentially contribute language cognition. We 13 are fixed among show convincing patterns. Using long-read DNA sequencing revealed hidden variation 200 ancestries, uncovering signatures selection not previously identified, possible balancing

Language: Английский

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Mechanisms and purpose of lowered action potential firing threshold in fast-spiking interneurons in the human neocortex

Published: Oct. 28, 2024

Abstract The mammalian brain exhibits various interspecies differences. Microanatomical and molecular differences in homologous neurons between species are best characterized the neocortical mantle, but purpose of these remains poorly understood. We performed whole-cell microelectrode recordings microanatomical analyses human fast-spiking parvalbumin (pvalb)-expressing interneurons tissue resected during surgery. Fast-spiking exhibited a lower action potential (AP) firing threshold humans than mice. Compared with mouse neurons, displayed an elongated axon initial segment (AIS), AIS was deficient low-voltage activated inhibitory Kv1 potassium channels. Contrarily, ion channels were prominent neurons. Computational interneuron model simulations revealed that human-type lowers AP shortens time lag for generation. Thus, supports fast in–fast out electrical circuit function pvalb which have electrically slow membrane kinetics somata. Teaser neocortex structural adaptations to shorten IN-OUT delay

Language: Английский

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If you please, draw me a neuron — linking evolutionary tinkering with human neuron evolution

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 89, P. 102260 - 102260

Published: Oct. 1, 2024

Language: Английский

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Human long noncoding RNA,VILMIR, is induced by major respiratory viral infections and modulates the host interferon response

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 29, 2024

ABSTRACT Long noncoding RNAs (lncRNAs) are a newer class of transcripts identified as key regulators biological processes. Here we aimed to identify novel lncRNA targets that play critical roles in major human respiratory viral infections by systematically mining large-scale transcriptomic datasets. Using bulk RNA-sequencing (RNA-seq) analysis, previously uncharacterized lncRNA, named virus inducible modulator interferon response ( VILMIR) , was consistently upregulated after vitro influenza infection across multiple epithelial cell lines and A subtypes. VILMIR also SARS-CoV-2 RSV . We experimentally confirmed the interferon-beta (IFN-β) treatment A549 line found expression robustly induced IFN-β dose time-specific manner. Single RNA-seq analysis bronchoalveolar lavage fluid (BALF) samples from COVID-19 patients uncovered various types including at least five immune cells. The upregulation cells further T monocyte lines, SUP-T1 THP-1, treatment. Finally, knockdown reduced magnitude host transcriptional responses Together, our results show is interferon-stimulated gene (ISG) regulates may be potential therapeutic target for upon mechanistic investigation. IMPORTANCE Identifying factors regulate developing new therapeutics. Human long have been regulatory during processes, however majority functions within antiviral remain unknown. In this study, influenza, SARS-CoV-2, RSV. demonstrated an several types. Our reveal present infections.

Language: Английский

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Aging-associated weakening of the action potential in fast-spiking interneurons in the human neocortex

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 27, 2024

ABSTRACT Aging is associated with the slowdown of neuronal processing and cognitive performance in brain; however, exact cellular mechanisms behind this deterioration humans are poorly elucidated. Recordings human acute brain slices prepared from tissue resected during surgery enable investigation changes age. Although neocortical fast-spiking cells widely implicated network activities underlying processes, they vulnerable to neurodegeneration. Herein, we analyzed electrical properties 147 interneurons neocortex samples 106 patients aged 11–84 years. By studying electrophysiological features action potentials passive membrane properties, report that potential overshoot significantly decreases spike half-width increases Moreover, maximum-rise speed (but not repolarization or afterhyperpolarization amplitude) changed age, suggesting a particular weakening sodium channel current generated soma. Cell measured as input resistance, time constant, cell capacitance remained unaffected by senescence. Thus, conclude shows significant This may contribute cortical functions aging.

Language: Английский

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A Human Touch: Hominid-Specific LRRC37B Regulates Axon Initial Segment Excitability

Epiliepsy currents/Epilepsy currents, Journal Year: 2024, Volume and Issue: 24(4), P. 286 - 288

Published: May 16, 2024

[Box: see text]

Language: Английский

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Super-resolution imaging of the neuronal cytoskeleton

npj Imaging, Journal Year: 2024, Volume and Issue: 2(1)

Published: Dec. 4, 2024

Language: Английский

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