Complex brain disorders are highly heritable and arise from a complex polygenic risk architecture. Many disease-associated loci are found in non-coding regions that house regulatory elements. These elements influence the transcription of target genes-many of which demonstrate cell-type-specific expression patterns-and thereby affect phenotypically relevant molecular pathways. Thus, cell-type-specificity must be considered when prioritizing candidate risk loci, variants and target genes. This Review discusses the use of high-throughput assays in human induced pluripotent stem cell-based neurodevelopmental models to probe genetic risk in a cell-type- and patient-specific manner. The application of massively parallel reporter assays in human induced pluripotent stem cells can characterize the human regulome and test the transcriptional responses of putative regulatory elements. Parallel CRISPR-based screens can further functionally dissect this genetic regulatory architecture. The integration of these emerging technologies could decode genetic risk into medically actionable information, thereby improving genetic diagnosis and identifying novel points of therapeutic intervention.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018778 | PMC |
| http://dx.doi.org/10.1038/s41593-020-00740-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A quantitative intracellular peptide binding assay reveals recognition determinants and context dependence of short linear motifs.
J Biol Chem
January 2025
Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA. Electronic address:
Transient protein-protein interactions play key roles in controlling dynamic cellular responses. Many examples involve globular protein domains that bind to peptide sequences known as Short Linear Motifs (SLiMs), which are enriched in intrinsically disordered regions of proteins. Here we describe a novel functional assay for measuring SLiM binding, called Systematic Intracellular Motif Binding Analysis (SIMBA).
View Article and Find Full Text PDFMassive Sequencing of V3-V4 Hypervariable Region in Pyogenic Liver Abscesses Reveals the Presence of Unusual Bacteria Not Detected by Classical Culture Methods.
Microorganisms
January 2025
Hospital Juárez de México, Mexico City 07760, Mexico.
Pyogenic liver abscesses (PLAs) are serious infections in which doctors often fail in identifying the causative agent due to microbiological limitations. These limitations in detecting uncommon pathogens complicate the treatment and recovery. Molecular techniques, like massive sequencing, enable the detection of uncommon pathogens and highlight the shortcomings of traditional cultures.
View Article and Find Full Text PDFThe Prevalence and Clinical Characteristics of -Associated Hearing Loss in 15,684 Hearing Loss Patients.
Genes (Basel)
January 2025
Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
belongs to the unconventional myosin superfamily, and the myosin IIIa protein localizes on the tip of the stereocilia of vestibular and cochlear hair cells. Deficiencies in have been reported to cause the deformation of hair cells into abnormally long stereocilia with an increase in spacing. is a rare causative gene of autosomal recessive sensorineural hearing loss (DFNB30), with only 13 cases reported to date.
View Article and Find Full Text PDFNovel Variants and Clinical Features of Hearing Loss in a Large Japanese Cohort.
Genes (Basel)
January 2025
Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Background/objectives: The gene is responsible for autosomal recessive non-syndromic sensorineural hearing loss and is assigned as DFNB18B. To date, 44 causative variants have been reported to cause non-syndromic hearing loss. However, the detailed clinical features for -associated hearing loss remain unclear.
View Article and Find Full Text PDFExploring the Potential of Genome-Wide Hybridization Capture Enrichment for Forensic DNA Profiling of Degraded Bones.
Genes (Basel)
December 2024
Australian Centre for Ancient DNA, The Environment Institute, School of Biological Sciences, The University of Adelaide, Adelaide, SA 5000, Australia.
Unlabelled: In many human rights and criminal contexts, skeletal remains are often the only available samples, and they present a significant challenge for forensic DNA profiling due to DNA degradation. Ancient DNA methods, particularly capture hybridization enrichment, have been proposed for dealing with severely degraded bones, given their capacity to yield results in ancient remains.
Background/objectives: This paper aims to test the efficacy of genome-wide capture enrichment on degraded forensic human remains compared to autosomal STRs analysis.
Want 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!