The extent to which the impact of regulatory genetic variants may depend on other factors, such as the expression levels of upstream transcription factors, remains poorly understood. Here we report a framework in which regulatory variants are first aggregated into sets, and using these as estimates of the total cis-genetic effects on a gene we model their non-additive interactions with the expression of other genes in the genome. Using 1220 lymphoblastoid cell lines across platforms and independent datasets we identify 74 genes where the impact of their regulatory variant-set is linked to the expression levels of networks of distal genes. We show that these networks are predominantly associated with tumourigenesis pathways, through which immortalised cells are able to rapidly proliferate. We consequently present an approach to define gene interaction networks underlying important cellular pathways such as cell immortalisation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969137 | PMC |
| http://dx.doi.org/10.1038/s41467-019-13762-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Glutamate Receptor-Like Gene AtGLR25 With Its Unusual Splice Variant Has a Role in Mediating Glutamate-Elicited Changes in Arabidopsis Root Architecture.
Plant Cell Environ
January 2025
College of Resources and Environmental Sciences, Department of Plant Nutrition, China Agricultural University, Beijing, Haidian, China.
The occurrence of external L-glutamate at the Arabidopsis root tip triggers major changes in root architecture, but the mechanism of -L-Glu sensing is unknown. Members of the family of GLUTAMATE RECEPTOR-LIKE (GLR) proteins are known to act as amino acid-gated Ca-permeable channels and to have signalling roles in diverse plant processes. To investigate the possible role of GLRs in the root architectural response to L-Glu, we screened a collection of mutants with T-DNA insertions in each of the 20 AtGLR genes.
View Article and Find Full Text PDFMassively parallel characterization of transcriptional regulatory elements.
Nature
January 2025
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.
View Article and Find Full Text PDFBiallelic variants in SREBF2 cause autosomal recessive spastic paraplegia.
J Genet Genomics
January 2025
Department of Medical Genetics and Center for Rare Diseases, the Second Affiliated Hospital of Zhejiang University School of Medicine, and Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation, Hangzhou, Zhejiang 310009, China; Nanhu Brain-computer Interface Institute, Hangzhou, Zhejiang 311100, China; MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310012, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai 200031, China; Lead contact. Electronic address:
Hereditary spastic paraplegias (HSPs) refer to a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by the degeneration of motor neurons. To date, a significant number of patients still have not received a definite genetic diagnosis. Therefore, identifying unreported causative genes continues to be of great importance.
View Article and Find Full Text PDFFunctional characterization of eQTLs and asthma risk loci with scATAC-seq across immune cell types and contexts.
Am J Hum Genet
January 2025
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201, USA. Electronic address:
cis-regulatory elements (CREs) control gene transcription dynamics across cell types and in response to the environment. In asthma, multiple immune cell types play an important role in the inflammatory process. Genetic variants in CREs can also affect gene expression response dynamics and contribute to asthma risk.
View Article and Find Full Text PDFThe ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease.
Autophagy
January 2025
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Although the relationship between macroautophagy/autophagy and Alzheimer disease (AD) is widely studied, the underlying mechanisms are poorly understood, especially the regulatory role of the initiation signaling of autophagy on AD. Here, we find that the ER transmembrane protein CANX (calnexin) is a novel interaction partner of the autophagy-inducing kinase ULK1 and is required for ULK1 recruitment to the ER under basal or starved conditions. Loss of CANX results in the inactivity of ULK1 kinase and inhibits autophagy flux.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!