BIN1 is a novel protein that interacts with the functionally critical Myc box regions at the N terminus of the MYC oncoprotein. BIN1 is structurally related to amphiphysin, a breast cancer-associated autoimmune antigen, and RVS167, a negative regulator of the yeast cell cycle, suggesting roles in malignancy and cell cycle control. Consistent with this likelihood, BIN1 inhibited malignant cell transformation by MYC. Although BIN1 is expressed in many normal cells, its levels were greatly reduced or undetectable in 14/27 carcinoma cell lines and 3/6 primary breast tumours. Deficits were functionally significant because ectopic expression of BIN1 inhibited the growth of tumour cells lacking endogenous message. We conclude that BIN1 is an MYC-interacting protein with features of a tumour suppressor.
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http://dx.doi.org/10.1038/ng0996-69 | DOI Listing |
Brief Bioinform
November 2024
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
Augmenting traditional genome-wide association studies (GWAS) with advanced machine learning algorithms can allow the detection of novel signals in available cohorts. We introduce "genome-wide association neural networks (GWANN)" a novel approach that uses neural networks (NNs) to perform a gene-level association study with family history of Alzheimer's disease (AD). In UK Biobank, we defined cases (n = 42 110) as those with AD or family history of AD and sampled an equal number of controls.
View Article and Find Full Text PDFActa Neuropathol Commun
January 2025
Department of Biological Sciences, Purdue University, 915 Mitch Daniels Blvd, West Lafayette, IN, USA.
Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer's disease (AD) being the most common type. Neuropathological examination remains the gold standard for accurate AD diagnosis, however, most that we know about AD genetics is based on Genome-Wide Association Studies (GWAS) of clinically defined AD. Such studies have identified multiple AD susceptibility variants with a significant portion of the heritability unexplained and highlighting the phenotypic and genetic heterogeneity of the clinically defined entity.
View Article and Find Full Text PDFJ Neurochem
January 2025
Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.
To date, several studies have integrated genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) data from bulk tissues to identify novel Alzheimer's disease (AD) genetic variants and susceptibility genes. However, there is highly cell-type-specific nature in different bulk eQTL data. Until now, eQTL data from different brain single cells have been reported.
View Article and Find Full Text PDFHeliyon
October 2024
Department of Anesthesiology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006, 17# Yong Wai Zheng Street, Nanchang City, Jiangxi Province, PR China.
bioRxiv
June 2024
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Genetic regulation of alternative splicing constitutes an important link between genetic variation and disease. Nonetheless, RNA splicing is regulated by both -acting elements and -acting splicing factors. Determining splicing events that are directed primarily by the - or -acting mechanisms will greatly inform our understanding of the genetic basis of disease.
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