Gene expression-based biological test for major depressive disorder: an advanced study

Watanabe, Shinya; Numata, Shusuke; Iga, Jun‐ichi; Kinoshita, Makoto; Umehara, Hiroki; Ishii, Kazuo; Ohmori, Tetsuro

doi:10.2147/ndt.s120038

Cited by 7 publications

(7 citation statements)

References 36 publications

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“…Studies have also revealed that several members of the Rho family of GTPase activators have neuronal functions, including regulating dendritic morphology and synaptic plasticity [26]. ARHGAP24 has been found to be a genetic marker to distinguish patients with major depression from healthy people [27]. In this study, we rst demonstrated that the SNPs in ARHGAP24 gene were associated with several aggressive behavioral traits.…”

Section: Discussionmentioning

confidence: 63%

A Single Nucleotide Polymorphism in Promoter of Porcine ARHGAP24 Gene Regulates Aggressive Behavior of Weaned Pigs After Mixing by Affecting the Binding of Transcription Factor P53

Guo

Zhao

et al. 2022

Preprint

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Background: Weaned pigs often have more aggressive behavior after mixing, which has negative effects on animal welfare and growth performance. Identification of functional single nucleotide polymorphisms (SNPs) related to aggressive behavior of pigs would provide valuable molecular markers of aggressive behavioral trait for genetic improvement program. Rho GTPase Activating Protein 24 (ARHGAP24) gene plays an important role in regulating the process of axon guidance, which may impact aggressive behavior of pigs. Results: By re-sequencing the entire coding region, partially adjacent introns and the 5’ and 3’ flanking regions, 6 and 4 SNPs were identified in the 5’ flanking region and 5’ untranslated region (UTR) of porcine ARHGAP24 gene, respectively. Association analyses revealed that 9 SNPs were significantly associated with aggressive behavioral traits (P = < 1.00 × 10−4 - 4.51 × 10−2), and their haplotypes were significantly associated with aggressive behavior (P = < 1.00 × 10−4 - 2.99 × 10−2). The core promoter region of ARHGAP24 gene was identified between -670 bp and -1113 bp. Furthermore, the luciferase activity of allele A of rs335052970 was significantly less than that of allele G, suggesting the transcriptional activity of ARHGAP24 gene was inhibited by allele A of rs335052970. It was identified that the transcription factor p53 bound to the transcription factor binding sites (TFBSs) containing allele A of rs335052970. In porcine primary neural cells, p53 bind to the target promoter region of ARHGAP24 gene, reduce its promoter transcriptional activity, and then reduce its messenger RNA (mRNA) and protein expression through axon guidance pathway.Conclusion: The results demonstrated that ARHGAP24 gene had significant genetic effects on aggressive behavioral traits of pigs. Therefore, rs335052970 in ARHGAP24 gene can be used as a molecular marker to select less aggressive pigs and improve animal welfare.

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Section: Discussionmentioning

confidence: 63%

A Single Nucleotide Polymorphism in Promoter of Porcine ARHGAP24 Gene Regulates Aggressive Behavior of Weaned Pigs After Mixing by Affecting the Binding of Transcription Factor P53

Guo

Zhao

et al. 2022

Preprint

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“…Studies have also revealed that several members of the Rho family of GTPase activators have neuronal functions, including regulating dendritic morphology and synaptic plasticity (Ramakers, 2002). ARHGAP24 has been found to be a genetic marker to distinguish patients with major depression from healthy people (Watanabe et al, 2017). In this study, we first demonstrated that SNPs in the 5′-flanking region of the ARHGAP24 gene were associated with several aggressive behavioral traits.…”

Section: Discussionmentioning

confidence: 68%

“…Therefore, the ARHGAP24 gene may play an important role in regulating the process of axon guidance, which then impacts aggressive behavior. In addition, previous studies have found that the ARHGAP24 gene is associated with human depression (Watanabe et al, 2017) and childhood autism (Coutton et al, 2015) accompanied by aggressive behavior. The ARHGAP24 gene is also related to the growth performance of pigs (Meng et al, 2017).…”

Section: Introductionmentioning

confidence: 96%

A Single-Nucleotide Polymorphism in the Promoter of Porcine ARHGAP24 Gene Regulates Aggressive Behavior of Weaned Pigs After Mixing by Affecting the Binding of Transcription Factor p53

Zhao

Guo

et al. 2022

Front. Cell Dev. Biol.

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Pigs are important biomedical model animals for the study of human neurological diseases. Similar to human aggressive behavior in children and adolescents, weaned pigs also show more aggressive behavior after mixing, which has negative effects on animal welfare and growth performance. The identification of functional single-nucleotide polymorphisms (SNPs) related to the aggressive behavior of pigs would provide valuable molecular markers of the aggressive behavioral trait for genetic improvement program. The Rho GTPase–activating protein 24 (ARHGAP24) gene plays an important role in regulating the process of axon guidance, which may impact the aggressive behavior of pigs. By resequencing the entire coding region, partially adjacent introns and the 5′ and 3′ flanking regions, six and four SNPs were identified in the 5′ flanking region and 5′ untranslated region (UTR) of the porcine ARHGAP24 gene, respectively. Association analyses revealed that nine SNPs were significantly associated with aggressive behavioral traits (p = < 1.00 × 10–4–4.51 × 10–2), and their haplotypes were significantly associated with aggressive behavior (p = < 1.00 × 10–4–2.99 × 10–2). The core promoter region of the ARHGAP24 gene has been identified between −670 and −1,113 bp. Furthermore, the luciferase activity of allele A of rs335052970 was significantly less than that of allele G, suggesting that the transcriptional activity of the ARHGAP24 gene was inhibited by allele A of rs335052970. It was identified that the transcription factor p53 bound to the transcription factor binding sites (TFBSs) containing allele A of rs335052970. In porcine primary neural cells, p53 binds to the target promoter region of the ARHGAP24 gene, reduces its promoter transcriptional activity, and then reduces its messenger RNA (mRNA) and protein expression. The results demonstrated that the ARHGAP24 gene had significant genetic effects on aggressive behavioral traits of pigs. Therefore, rs335052970 in the ARHGAP24 gene can be used as a molecular marker to select the less aggressive pigs.

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“… 30 One study found that the expression of SLC6A4 was significantly higher in patients with schizophrenia and BD. 31 This indicates that studies should explain the relationship between SLC6A4 and BD. miRNAs play an important role in biomarker studies, which are especially needed for brain-based diseases, such as major depressive disorder.…”

Section: Discussionmentioning

confidence: 99%

Biomarker potential of hsa-miR-145-5p in peripheral whole blood of manic bipolar I patients

Tekin¹,

Asoğlu²,

Ay³

et al. 2022

Brazilian Journal of Psychiatry

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Objective: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers. Methods: We evaluated the expression profile of six candidate miRNAs ( hsa-miR-145-5p , hsa-miR-376a-3p , hsa-miR-3680-5p , hsa-miR-4253-5p , hsa-miR-4482-3p , and hsa-miR-4725 ) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis. Results: Four miRNAs were upregulated ( hsa-miR-376a-3p , hsa-miR-3680-5p , hsa-miR-4253-5p , hsa-miR-4482-3p ) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase ( DDC ) gene. The area under the curve of hsa-miR-145-5p was 0.987. Conclusion: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene.

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Gene expression-based biological test for major depressive disorder: an advanced study

Cited by 7 publications

References 36 publications

A Single Nucleotide Polymorphism in Promoter of Porcine ARHGAP24 Gene Regulates Aggressive Behavior of Weaned Pigs After Mixing by Affecting the Binding of Transcription Factor P53

A Single Nucleotide Polymorphism in Promoter of Porcine ARHGAP24 Gene Regulates Aggressive Behavior of Weaned Pigs After Mixing by Affecting the Binding of Transcription Factor P53

A Single-Nucleotide Polymorphism in the Promoter of Porcine ARHGAP24 Gene Regulates Aggressive Behavior of Weaned Pigs After Mixing by Affecting the Binding of Transcription Factor p53

Biomarker potential of hsa-miR-145-5p in peripheral whole blood of manic bipolar I patients

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