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Genetic Research of Neurodegenerative and Psychiatric Disorders

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (25 May 2021) | Viewed by 16105

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Special Issue Editors

Prof. Dr. Concetta Crisafulli

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Guest Editor

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98122 Messina, Italy
Interests: psychiatric genetics; molecular pathway; neurodegenerative disorder genetics; pharmacogenetics; neuroscience

Dr. Marco Calabrò

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Co-Guest Editor

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, 98125, Italy
Interests: psychiatric disorders; neurodegenerative disorders; neurodevelopmental disorders; genetics; pharmacogenetics; bioinformatics

Special Issue Information

Dear Colleagues,

The brain and its functions have always been a source of wonder and many questions. Studies on the pathologies afflicting the brain, either of psychiatric or neurodegenerative nature, are flourishing. Unfortunately, these disorders have inherited the sheer complexity of the brain. In recent decades, numerous researchers have struggled to identify the etiopathogenesis of both psychiatric and neurodegenerative pathologies. However, genetic anomalies are thought to be a relevant part of the puzzle. In the past century, the first associations between genetic variations and these disorders caused a rush to find key genes whose alterations are causative of mental pathologies. Unfortunately, the hope of finding specific genetic causes was wrecked by the not-so-significant data obtained from many large genome-wide analyses. Since then, we have understood that, apart from few exceptions, there are no single causative genes, but rather multiple genetic alterations and environmental variables, each with a weak effect that concur to increase the risk of mental disorders. We began to use novel approaches in order to identify the possible causative biological mechanisms: from the traditional neurocentric approach, to the inclusion of non-neuronal cell subtypes; from the focus on neurotransmission processes to the inclusion of several other processes, including immune/inflammation, oxidative stress; from the single-gene approach to pathway analysis. This field continues to be exciting and rich with novel discoveries; more and more data are amassing and are being elaborated upon thanks to the contributions of researchers all over the world.

In this Special Issue, we will present the state of the art on the genetics and genomic components of neurodegenerative and psychiatric disorders, assembling the most recent advances and original designs in one place, to provide a picture reflecting the biological/genetical background associated with disease pathogenesis and its role/significance in treatment.

Prof. Dr. Concetta Crisafulli
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

neurodegeneration
psychiatric disorders
genetics
neurons
glia
neurotransmission
oxidative stress
inflammation
immune system
pathway analysis

Published Papers (5 papers)

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Research

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25 pages, 2647 KiB

Open AccessArticle

by Line K. M. Lybech, Marco Calabró, Silvana Briuglia, Antonio Drago and Concetta Crisafulli

Genes 2021, 12(10), 1482; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12101482 - 23 Sep 2021

Cited by 5 | Viewed by 2053

Abstract

Suicide in Bipolar Disorder (BD) is a relevant clinical concern. Genetics may shape the individual risk for suicide behavior in BD, together with known clinical factors. The lack of consistent replication in BD may be associated with its multigenetic component. In the present contribution we analyzed a sample of BD individuals (from STEP-BD database) to identify the genetic variants potentially associated with three different suicide-related phenotypes: (1) a feeling that the life was not worth living; (2) fantasies about committing a violent suicide; (3) previous attempted suicide. The sample under analysis included 1115 BD individuals. None of the SNPs reached genome-wide significance. However, a trend of association was evidenced for rs2767403, an intron variant of AOPEP gene, in association with phenotype #1 (p = 5.977 × 10⁻⁶). The molecular pathway analysis showed a significant enrichment in all the investigated phenotypes on pathways related to post synaptic signaling, neurotransmission and neurodevelopment. Further, NOTCH signaling or the γ-aminobutyric acid (GABA)-ergic signaling were found to be associated with specific suicide-related phenotypes. The present investigation contributes to the hypothesis that the genetic architecture of suicide behaviors in BD is related to alteration of entire pathways rather than single genes. In particular, our molecular pathway analysis points on some specific molecular events that could be the focus of further research in this field. Full article

(This article belongs to the Special Issue Genetic Research of Neurodegenerative and Psychiatric Disorders)

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11 pages, 1002 KiB

Open AccessArticle

Genetic Predisposition to Alzheimer’s Disease Is Associated with Enlargement of Perivascular Spaces in Centrum Semiovale Region

by Iacopo Ciampa, Grégory Operto, Carles Falcon, Carolina Minguillon, Manuel Castro de Moura, David Piñeyro, Manel Esteller, Jose Luis Molinuevo, Roderic Guigó, Arcadi Navarro, Juan Domingo Gispert, Natalia Vilor-Tejedor and for the ALFA Study

Genes 2021, 12(6), 825; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12060825 - 27 May 2021

Cited by 6 | Viewed by 3823

Abstract

This study investigated whether genetic factors involved in Alzheimer’s disease (AD) are associated with enlargement of Perivascular Spaces (ePVS) in the brain. A total of 680 participants with T2-weighted MRI scans and genetic information were acquired from the ALFA study. ePVS in the basal ganglia (BG) and the centrum semiovale (CS) were assessed based on a validated visual rating scale. We used univariate and multivariate logistic regression models to investigate associations between ePVS in BG and CS with BIN1-rs744373, as well as APOE genotypes. We found a significant association of the BIN1-rs744373 polymorphism in the CS subscale (p value = 0.019; OR = 2.564), suggesting that G allele carriers have an increased risk of ePVS in comparison with A allele carriers. In stratified analysis by APOE-ε4 status (carriers vs. non-carriers), these results remained significant only for ε4 carriers (p value = 0.011; OR = 1.429). To our knowledge, the present study is the first suggesting that genetic predisposition for AD is associated with ePVS in CS. These findings provide evidence that underlying biological processes affecting AD may influence CS-ePVS. Full article

(This article belongs to the Special Issue Genetic Research of Neurodegenerative and Psychiatric Disorders)

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10 pages, 1727 KiB

Open AccessArticle

Mitochondrial D-Loop Region Methylation and Copy Number in Peripheral Blood DNA of Parkinson’s Disease Patients

by Andrea Stoccoro, Adam R. Smith, Filippo Baldacci, Claudia Del Gamba, Annalisa Lo Gerfo, Roberto Ceravolo, Katie Lunnon, Lucia Migliore and Fabio Coppedè

Genes 2021, 12(5), 720; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12050720 - 12 May 2021

Cited by 14 | Viewed by 2828

Abstract

Altered mitochondrial DNA (mtDNA) methylation has been detected in several human pathologies, although little attention has been given to neurodegenerative diseases. Recently, altered methylation levels of the mitochondrial displacement loop (D-loop) region, which regulates mtDNA replication, were observed in peripheral blood cells of Alzheimer’s disease and amyotrophic lateral sclerosis patients. However, nothing is yet known about D-loop region methylation levels in peripheral blood of Parkinson’s disease (PD) patients. In the current study, we investigated D-loop methylation levels and mtDNA copy number in peripheral blood of 30 PD patients and 30 age- and sex-matched control subjects. DNA methylation analyses have been performed by means of methylation-sensitive high-resolution melting (MS-HRM) and pyrosequencing techniques, while mtDNA copy number was analyzed by quantitative PCR. MS-HRM and pyrosequencing analyses provided very similar D-loop methylation levels in PD patients and control subjects, and no differences between the two groups have been observed. Treatment with L-dopa and duration of the disease had no effect on D-loop methylation levels in PD patients. Additionally, mtDNA copy number did not differ between PD patients and control subjects. Current results suggest that D-loop methylation levels are not altered in peripheral blood of PD patients nor influenced by dopaminergic treatment. Full article

(This article belongs to the Special Issue Genetic Research of Neurodegenerative and Psychiatric Disorders)

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18 pages, 1562 KiB

Open AccessArticle

Clustering Analysis Supports the Detection of Biological Processes Related to Autism Spectrum Disorder

by Leonardo Emberti Gialloreti, Roberto Enea, Valentina Di Micco, Daniele Di Giovanni and Paolo Curatolo

Genes 2020, 11(12), 1476; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11121476 - 09 Dec 2020

Cited by 7 | Viewed by 1912

Abstract

Genome sequencing has identified a large number of putative autism spectrum disorder (ASD) risk genes, revealing possible disrupted biological pathways; however, the genetic and environmental underpinnings of ASD remain mostly unanswered. The presented methodology aimed to identify genetically related clusters of ASD individuals. By using the VariCarta dataset, which contains data retrieved from 13,069 people with ASD, we compared patients pairwise to build “patient similarity matrices”. Hierarchical-agglomerative-clustering and heatmapping were performed, followed by enrichment analysis (EA). We analyzed whole-genome sequencing retrieved from 2062 individuals, and isolated 11,609 genetic variants shared by at least two people. The analysis yielded three clusters, composed, respectively, by 574 (27.8%), 507 (24.6%), and 650 (31.5%) individuals. Overall, 4187 variants (36.1%) were common to the three clusters. The EA revealed that the biological processes related to the shared genetic variants were mainly involved in neuron projection guidance and morphogenesis, cell junctions, synapse assembly, and in observational, imitative, and vocal learning. The study highlighted genetic networks, which were more frequent in a sample of people with ASD, compared to the overall population. We suggest that itemizing not only single variants, but also gene networks, might support ASD etiopathology research. Future work on larger databases will have to ascertain the reproducibility of this methodology. Full article

(This article belongs to the Special Issue Genetic Research of Neurodegenerative and Psychiatric Disorders)

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Review

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27 pages, 959 KiB

Open AccessReview

Genomic Mosaicism Formed by Somatic Variation in the Aging and Diseased Brain

by Isabel Costantino, Juliet Nicodemus and Jerold Chun

Genes 2021, 12(7), 1071; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12071071 - 14 Jul 2021

Cited by 14 | Viewed by 4791

Abstract

Over the past 20 years, analyses of single brain cell genomes have revealed that the brain is composed of cells with myriad distinct genomes: the brain is a genomic mosaic, generated by a host of DNA sequence-altering processes that occur somatically and do not affect the germline. As such, these sequence changes are not heritable. Some processes appear to occur during neurogenesis, when cells are mitotic, whereas others may also function in post-mitotic cells. Here, we review multiple forms of DNA sequence alterations that have now been documented: aneuploidies and aneusomies, smaller copy number variations (CNVs), somatic repeat expansions, retrotransposons, genomic cDNAs (gencDNAs) associated with somatic gene recombination (SGR), and single nucleotide variations (SNVs). A catch-all term of DNA content variation (DCV) has also been used to describe the overall phenomenon, which can include multiple forms within a single cell’s genome. A requisite step in the analyses of genomic mosaicism is ongoing technology development, which is also discussed. Genomic mosaicism alters one of the most stable biological molecules, DNA, which may have many repercussions, ranging from normal functions including effects of aging, to creating dysfunction that occurs in neurodegenerative and other brain diseases, most of which show sporadic presentation, unlinked to causal, heritable genes. Full article

(This article belongs to the Special Issue Genetic Research of Neurodegenerative and Psychiatric Disorders)

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