212 papers
This paper introduces Blockbuster, a deterministic program that achieves the theoretical limits for inferring recent demographic history from genome-wide Site Frequency Spectra by accurately estimating the timing and intensity of population size changes while offering a method to mitigate the confounding effects of population structure.
This study utilizes CRISPR/Cas9-generated mouse and human embryonic stem cell models to demonstrate that heterozygous PCDH19 mutations cause PCDH19-Cluster Epilepsy through specific gene expression defects in developmental and neuronal pathways, while revealing that neurite morphology correlates directly with the levels of wild-type PCDH19 protein.
This study demonstrates that analyzing CETP's alternative splicing isoforms, rather than just the protein as a whole, reveals critical tissue-specific genetic regulations and causal impacts on human traits, including cardiovascular disease and endocrine functions, while suggesting that previously observed epistatic interactions may be mediated through splicing mechanisms.
This study demonstrates that the T27P mutation in the non-prion domain of the yeast protein Rnq1 creates a transmission barrier by preventing the propagation of wild-type prion conformations and promoting the formation of liquid-like aggregates, thereby revealing how interactions between non-prion and prion domains dictate amyloid versus liquid-like assembly and influence protein misfolding disease mechanisms.
Loss of Hippo signaling effectors Yap1 and Wwtr1 disrupts optic fissure closure by causing cells at the fissure edges to lose their retinal pigment epithelium fate and transdifferentiate into unpigmented neural retina, thereby creating a steric block that leads to coloboma.
This study challenges the recent hypothesis that fungal spores contain a single haploid chromosome set distributed across multiple nuclei, presenting fluorescent microscopy, UV mutagenesis, and genome sequencing data that instead confirm the nuclei are mitotic copies containing multiple chromosome sets.
This study demonstrates that while Black Soldier Fly larvae growth traits exhibit low to moderate heritability and significant dominance effects, selective breeding can achieve substantial genetic gain provided that genotype-by-diet interactions are strategically managed.
This study utilizes Multiplexed Parallel Reporter Assays to characterize variants associated with Cerebral Small Vessel Disease, identifying 26 allele-specific enhancers and mechanistically validating a functional SNV in the Versican gene that modulates transcriptional activity via NKX3.1 binding.
The paper introduces ENGINE, an efficient, supervised variance-component framework that learns optimal combinations of multiple environmental exposures to accurately model polygenic gene-environment interactions at biobank scale, demonstrating superior power and accuracy in capturing GxE variance compared to single-exposure or principal component approaches.
This study utilizes the human bicistronic gene SMIM45 to demonstrate that diverse evolutionary mechanisms, ranging from simple Alu insertions to complex "cultivator gene" processes, drive the origination and maturation of super-enhancers and super-silencers over hundreds of millions of years, ultimately facilitating the birth of a human-specific de novo gene expressed in the embryonic brain.
This study demonstrates that the central KOW2-3 domains of the transcription elongation factor Spt5 collaborate with the Pol II stalk (Rpb4/7) to function as a recruitment platform that coordinates 3'-end processing and maintains chromatin integrity during transcription elongation in *Saccharomyces cerevisiae*.
This study demonstrates that GBLUP-based multi-kernel models effectively estimate genetic variance and predict the performance of maize single-cross hybrids when parental information is available, while also revealing that Stiff Stalk germplasm has lost significant grain yield variance in intermediate-flowering groups, thereby highlighting both the potential and limitations of current US maize breeding strategies.
This study utilizes genome-wide SNP markers to reveal three distinct genetic groups and unique demographic histories of Pacific cod in Japanese waters, demonstrating that carefully selected outlier SNPs significantly enhance stock identification accuracy for sustainable fisheries management.
This study demonstrates that the Drosophila protein Putzig safeguards genome integrity in the female germline by acting as a central hub that facilitates Piwi-mediated transposon silencing through a two-tiered mechanism: promoting piRNA precursor transcription at clusters and licensing heterochromatin formation via Lsd1 recruitment.
This study establishes that cellular morphology is a polygenic trait governed by distributed transcriptional variation rather than dominant gene-phenotype relationships, demonstrating that a latent-space autoencoder can predict morphological features from gene expression across diverse donors and validating specific molecular anchors through CRISPR perturbation and transcriptome-wide association analyses.
This study demonstrates that rare, focal somatic mutations in neurodegeneration-related genes contribute to the etiology of sporadic amyotrophic lateral sclerosis and frontotemporal dementia, suggesting that localized genetic alterations can drive widespread neurodegeneration.
This paper introduces Rosalind, a DNA foundation model that overcomes the proximity bias of traditional gene-mapping approaches by accurately predicting distal variant-gene regulatory relationships from sequence, thereby successfully identifying novel osteoporosis risk genes and demonstrating a scalable framework for translating genetic insights into drug discovery.
This study demonstrates that a Sire Maternal Grandsire model effectively disentangles paternal and maternal genetic contributions to lifetime productivity in tropical dairy cattle, revealing a significant maternal-line influence and providing a more stable and predictive breeding framework than the classical Animal Model.
The paper introduces RETrace2, a high-resolution single-cell dual-omic method that leverages highly mutable homopolymers and sparse methylation profiling to simultaneously reconstruct detailed cell lineage trees and identify cell types with unprecedented accuracy in both in vitro and in vivo models.
This study reveals that the asexual tardigrade *Hypsibius exemplaris* maintains genome-wide heterozygosity through a modified meiotic process involving the failure of meiosis I followed by a meiosis II-like division, thereby challenging the notion that asexual reproduction inevitably leads to reduced genetic diversity.