Hasil untuk "Genetics"

McKinsey L. Goodenberger, R. Jenkins

C. Klein, A. Westenberger

Judy H. Cho

Mehrdad Hajibabaei, G. Singer, P. Hebert et al.

J. Poland, Trevor W. Rife

P. Ridge, M. Ebbert, J. Kauwe

Alzheimer's disease is the most common form of dementia and is the only top 10 cause of death in the United States that lacks disease-altering treatments. It is a complex disorder with environmental and genetic components. There are two major types of Alzheimer's disease, early onset and the more common late onset. The genetics of early-onset Alzheimer's disease are largely understood with variants in three different genes leading to disease. In contrast, while several common alleles associated with late-onset Alzheimer's disease, including APOE, have been identified using association studies, the genetics of late-onset Alzheimer's disease are not fully understood. Here we review the known genetics of early- and late-onset Alzheimer's disease.

M. Rose, F. Winston, P. Hieter

Sudhir Kumar, K. Tamura, M. Nei

J. Thoday

F. Sherman, G. Fink, J. Hicks

N. Bardeesy, R. DePinho

Anthony H. D. Brown, M. Clegg, A. Kahler et al.

P. Lewis, Sudhir Kumar, K. Tamura et al.

S. Cheetham, F. Gruhl, J. Mattick et al.

Cancer is a disease of aberrant gene expression. While the genetic causes of cancer have been intensively studied, it is becoming evident that a large proportion of cancer susceptibility cannot be attributed to variation in protein-coding sequences. This is highlighted by genome-wide association studies in cancer that reveal that more than 80% of cancer-associated SNPs occur in noncoding regions of the genome. In this review, we posit that a significant fraction of the genetic aetiology of cancer is exacted by noncoding regulatory sequences, particularly by long noncoding RNAs (lncRNAs). Recent studies indicate that several cancer risk loci are transcribed into lncRNAs and these transcripts play key roles in tumorigenesis. We discuss the epigenetic and other mechanisms through which lncRNAs function and how they contribute to each stage of cancer progression, understanding of which will be crucial for realising new opportunities in cancer diagnosis and treatment. Long noncoding RNAs play important roles in almost every aspect of cell biology from nuclear organisation and epigenetic regulation to post-transcriptional regulation and splicing, and we link these processes to the hallmarks and genetics of cancer. Finally, we highlight recent progress and future potential in the application of lncRNAs as therapeutic targets and diagnostic markers.

K. Boycott, Megan R. Vanstone, D. Bulman et al.

C. Børsting, N. Morling

D. Geschwind, J. Flint

Kun Zhao, Siyuan Dai, Yingying Zhang et al.

Early detection of Alzheimer's disease (AD) requires models capable of integrating macro-scale neuroanatomical alterations with micro-scale genetic susceptibility, yet existing multimodal approaches struggle to align these heterogeneous signals. We introduce R-GenIMA, an interpretable multimodal large language model that couples a novel ROI-wise vision transformer with genetic prompting to jointly model structural MRI and single nucleotide polymorphisms (SNPs) variations. By representing each anatomically parcellated brain region as a visual token and encoding SNP profiles as structured text, the framework enables cross-modal attention that links regional atrophy patterns to underlying genetic factors. Applied to the ADNI cohort, R-GenIMA achieves state-of-the-art performance in four-way classification across normal cognition (NC), subjective memory concerns (SMC), mild cognitive impairment (MCI), and AD. Beyond predictive accuracy, the model yields biologically meaningful explanations by identifying stage-specific brain regions and gene signatures, as well as coherent ROI-Gene association patterns across the disease continuum. Attention-based attribution revealed genes consistently enriched for established GWAS-supported AD risk loci, including APOE, BIN1, CLU, and RBFOX1. Stage-resolved neuroanatomical signatures identified shared vulnerability hubs across disease stages alongside stage-specific patterns: striatal involvement in subjective decline, frontotemporal engagement during prodromal impairment, and consolidated multimodal network disruption in AD. These results demonstrate that interpretable multimodal AI can synthesize imaging and genetics to reveal mechanistic insights, providing a foundation for clinically deployable tools that enable earlier risk stratification and inform precision therapeutic strategies in Alzheimer's disease.

Ellen Baake, Fernando Cordero, Enrico Di Gaspero et al.

We establish connections between the absorption probabilities of a class of birth-death processes with killing, and the stationary tail of a related class of birth-death processes with catastrophes. The major ingredients of the proofs are a decomposition of the dynamics of these processes, a Feynman--Kac type relationship for Markov chains with reset and rebirth, and the concept of Siegmund duality, which allows us to invert the relationship between the processes. We apply our results to a pair of ancestral processes in population genetics, namely the killed ancestral selection graph and the pruned lookdown ancestral selection graph, in a finite population setting and its diffusion limit.

Xiaoying Cai, Yao He, Iris Yu et al.

Abstract Due to envelope differences between Gram-positive and Gram-negative bacteria, engineering precision bactericidal contractile nanomachines requires atomic-level understanding of their structures; however, only those killing Gram-negative bacteria are currently known. Here, we report the atomic structures of an engineered diffocin, a contractile syringe-like molecular machine that kills the Gram-positive bacterium Clostridioides difficile. Captured in one pre-contraction and two post-contraction states, each structure fashions six proteins in the bacteria-targeting baseplate, two proteins in the energy-storing trunk, and a collar linking the sheath with the membrane-penetrating tube. Compared to contractile machines targeting Gram-negative bacteria, major differences reside in the baseplate and contraction magnitude, consistent with target envelope differences. The multifunctional hub-hydrolase protein connects the tube and baseplate and is positioned to degrade peptidoglycan during penetration. The full-length tape measure protein forms a coiled-coil helix bundle homotrimer spanning the entire diffocin. Our study offers mechanical insights and principles for designing potent protein-based precision antibiotics.