A novel discovery platform for targeted drug repurposing: application for psychiatric disorders

The Lancet Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Chromosome 4 Duplication Associated with Strabismus Leads to Gene Expression Changes in iPSC-Derived Cortical Neurons

Genes, Journal Year: 2025, Volume and Issue: 16(1), P. 80 - 80

Published: Jan. 12, 2025

Background/Objectives: Strabismus is the most common ocular disorder of childhood. Three rare, recurrent genetic duplications have been associated with both esotropia and exotropia, but mechanisms by which they contribute to strabismus are unknown. This work aims investigate smallest three, a 23 kb duplication on chromosome 4 (hg38|4:25,554,985-25,578,843). Methods: Using CRISPR bridging oligos, we introduced into Kolf2.1J iPSC line. We differentiated parent line cortical neurons using three-dimensional differentiation protocol, performed bulk RNASeq neural progenitors (day 14) 63). Results: successfully iPSCs nucleofecting oligo for newly formed junction along cas9 ribonucleoparticles. confirmed that cells had tandem without inversion or deletion. The reliably. There were total 37 differentially expressed genes (DEGs) at day 63, 25 downregulated 12 upregulated. 55 DEGs 14, 18 also 63. included number protocadherins, several involved in neuronal development, including SLITRK2, CSMD1, VGF, unknown function. Conclusions: A copy variant (CNV) confers risk affects gene expression highlighting likely results from abnormal identifying new pathways further research pathophysiology strabismus.

Language: Английский

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Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 28, 2024

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated protocadherin-related 15 (PCDH15) gene in onset disorders, such as bipolar disorder (BD). To further investigate we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified causative Usher syndrome, which presents with visual and auditory impairments, our mice Pcdh15 homozygous deletion (Pcdh15-null) did exhibit observable structural abnormalities either retina or inner ear. The Pcdh15-null showed very high levels spontaneous motor activity was too disturbed to perform standard behavioral testing. heterozygous (Pcdh15-het) exhibited enhanced locomotor activity, reduced prepulse inhibition, diminished cliff avoidance behavior. These observations agreed symptoms observed patients various disorders several models diseases. Specifically, hyperactivity may mirror manic episodes BD. obtain more physiological, long-term quantification hyperactive phenotype, implanted nano tag® sensor chips animals, enable continuous monitoring both body temperature. During light-off period, elevated temperature compared wild-type (WT) mice. decreased during light-on period. Comprehensive brain visualized using c-Fos mapping, assessed peak trough. There stark contrast between distribution expression WT brains periods. results provide valuable insights into neural basis thermal characteristics Pcdh15-deletion Therefore, can be novel for BD mania other strong genetic component that satisfies construct surface validity.

Language: Английский

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Effects of Copy Number Variations in the Plectin (PLEC) Gene on the Growth Traits and Meat Quality of Leizhou Black Goats

Animals, Journal Year: 2023, Volume and Issue: 13(23), P. 3651 - 3651

Published: Nov. 25, 2023

The plectin (PLEC) gene is crucial in regulating muscle development and maintaining the cytoskeleton. An abnormal expression of PLEC can lead to atrophy muscular dystrophy. In a previous study, we found that Leizhou black goats exhibit abundant structural variations gene. However, genetic effects these on growth traits meat quality are not fully understood. this three copy number (CNVs) were identified population 417 goats, using quantitative polymerase chain reaction (qPCR) technology. Population distribution analysis revealed high abundance various types CNVs. mRNA was be highly expressed tissue remained consistently from 1 month 24 months after birth. Specifically, gain type CNV-1 (chr14: 81056401-81064800) showed significant association with (p < 0.01). sequence shares similarities domain superfamilies associated skin disease. Furthermore, there differences chest circumference, body weight, carcass cross-sectional area longissimus dorsi lumbar muscle, shear stress between different 0.05). Notably, demonstrated better phenotypic values compared those loss normal types. These findings suggest could play role making it potential marker for assisted selection goat breeding.

Language: Английский

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Contribution of copy number variants on antipsychotic treatment response in Han Chinese patients with schizophrenia

EBioMedicine, Journal Year: 2024, Volume and Issue: 105, P. 105195 - 105195

Published: June 14, 2024

Response to antipsychotic drugs (APD) varies greatly among individuals and is affected by genetic factors. This study aims demonstrate genome-wide associations between copy number variants (CNVs) response APD in patients with schizophrenia.

Language: Английский

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One Copy Number Variation within the Angiopoietin-1 Gene Is Associated with Leizhou Black Goat Meat Quality

Animals, Journal Year: 2024, Volume and Issue: 14(18), P. 2682 - 2682

Published: Sept. 14, 2024

The ANGPT1 gene plays a crucial role in the regulation of angiogenesis and muscle growth, with previous studies identifying copy number variations (CNVs) within this among Leizhou black goats. In study, we investigated three CNVs 417 individuals LZBG using quantitative PCR (qPCR), examining impact different CNV types on expression their associations growth meat quality traits. Notably, CNV-1 (ARS1_chr14:24950001-24953600) overlaps protein-coding regions conserved domains; its gain-of-copies genotype (copies ≥ 3) was significantly correlated mRNA tissue (p < 0.01). Furthermore, demonstrated significant correlations various phenotypic traits, including carcass weight, body shear stress, chest circumference, cross-sectional area longissimus dorsi muscle. These findings indicate that may serve as valuable marker for selecting goats exhibiting enhanced muscular development characteristics, thereby holding potential applications targeted breeding programs aimed at improving quality.

Language: Английский

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Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 8, 2024

Genetic factors significantly influence the pathogenesis of psychiatric disorders. However, specific pathogenic mechanisms underlying these effects are not fully elucidated. Recent extensive genomic studies implicate protocadherin related 15 (PCDH15) gene in onset disorders such as bipolar disorder (BD). To further investigate disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified causative for Usher syndrome, which leads to visual and auditory impairments, our Pcdh15 homozygous deletion mice (Pcdh15-null) did show observable structural abnormalities either retina or inner ear. heterozygous (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, diminished cliff avoidance behavior. These observations aligned with symptoms observed various patients certain disease models. Specifically, hyperactivity may mirror manic episodes BD. achieve more physiological, long-term quantification hyperactive phenotype, implanted nano tag^® sensor chips animals, enabling continuous monitoring both activity body temperature. During light-off period, Pcdh15-null elevated temperature compared those wild-type (WT). decreased during light-on period. Comprehensive brain was visualized using c-Fos mapping, assessed peak trough. There stark contrast between distribution expression WT brains periods. results provide valuable insights into neural basis behavioral thermal characteristics Pcdh15-deletion mice. Therefore, can be novel BD mania other strong genetic component that satisfies construct surface validity.

Language: Английский

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Editorial Overview: Molecular neuroscience

Current Opinion in Neurobiology, Journal Year: 2024, Volume and Issue: 86, P. 102873 - 102873

Published: April 2, 2024

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CNVs and Human Well-being: Integrating Psychiatric, Physical, and Socioeconomic Perspectives

Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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