Journal of neurogenetics最新文献

{"title":"Change in gene expression levels of GABA, glutamate and neurosteroid pathways due to acoustic trauma in the cochlea.","authors":"Meltem Cerrah Gunes,&nbsp;Murat Salih Gunes,&nbsp;Alperen Vural,&nbsp;Fatma Aybuga,&nbsp;Arslan Bayram,&nbsp;Keziban Korkmaz Bayram,&nbsp;Mehmet Ilhan Sahin,&nbsp;Muhammet Ensar Dogan,&nbsp;Sevda Yesim Ozdemir,&nbsp;Yusuf Ozkul","doi":"10.1080/01677063.2021.1904922","DOIUrl":"https://doi.org/10.1080/01677063.2021.1904922","url":null,"abstract":"<p><p>The characteristic feature of noise-induced hearing loss (NIHL) is the loss or malfunction of the outer hair cells (OHC) and the inner hair cells (IHC) of the cochlea. 90-95% of the spiral ganglion neurons, forming the cell bodies of cochlear nerve, synapse with the IHCs. Glutamate is the most potent excitatory neurotransmitter for IHC-auditory nerve synapses. Excessive release of glutamate in response to acoustic trauma (AT), may cause excitotoxicity by causing damage to the spiral ganglion neurons (SGN) or loss of the spiral ganglion dendrites, post-synaptic to the IHCs. Another neurotransmitter, GABA, plays an important role in the processing of acoustic stimuli and central regulation after peripheral injury, so it is potentially related to the regulation of hearing function and sensitivity after noise. The aim of this study is to evaluate the effect of AT on the expressions of glutamate excitotoxicity, GABA inhibition and neurosteroid synthesis genes.We exposed 24 BALB/c mice to AT. Controls were sacrificed without exposure to noise, Post-AT(1) and Post-AT(15) were sacrificed on the 1st and 15th day, respectively, after noise exposure. The expressions of various genes playing roles in glutamate, GABA and neurosteroid pathways were compared between groups by real-time PCR.Expressions of <i>Cyp11a1</i>, <i>Gls</i>, <i>Gabra1</i>, <i>Grin2b</i>, <i>Sult1a1</i>, <i>Gad1,</i> and <i>Slc1a2</i> genes in Post-AT(15) mice were significantly decreased in comparison to control and Post-AT(1) mice. No significant differences in the expression of <i>Slc6a1</i> and <i>Slc17a8</i> genes was detected.These findings support the possible role of balance between glutamate excitotoxicity and GABA inhibition is disturbed during the post AT days and also the synthesis of some neurosteroids such as pregnenolone sulfate may be important in this balance.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"35 1","pages":"45-57"},"PeriodicalIF":1.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2021.1904922","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25568122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Description of clinical features and genetic analysis of one ultra-rare (SPG64) and two common forms (SPG5A and SPG15) of hereditary spastic paraplegia families.","authors":"Mahdieh Pashaei,&nbsp;Atefeh Davarzani,&nbsp;Reza Hajati,&nbsp;Babak Zamani,&nbsp;Shahriar Nafissi,&nbsp;Farzaneh Larti,&nbsp;Yalda Nilipour,&nbsp;Mohammad Rohani,&nbsp;Afagh Alavi","doi":"10.1080/01677063.2021.1895146","DOIUrl":"https://doi.org/10.1080/01677063.2021.1895146","url":null,"abstract":"<p><p>Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder, characterized by lower-limb spasticity and weakness. To date, more than 82 loci/genes (SPG1-SPG82) have been identified that contribute to the cause of HSP. Despite the use of next-generation sequencing-based methods, genetic-analysis has failed in the finding of causative genes in more than 50% of HSP patients, indicating a more significant heterogeneity and absence of a given phenotype-genotype correlation. Here, we performed whole-exome sequencing (WES) to identify HSP-causing genes in three unrelated-Iranian probands. Candidate variants were detected and confirmed in the probands and co-segregated in the family members. The phenotypic data gathered and compared with earlier cases with the same sub-types of disease. Three novel homozygous variants, c.978delT; p.Q327Kfs*39, c.A1208G; p.D403G and c.3811delT; p.S1271Lfs*44, in known HSP-causing genes including <i>ENTPD1</i>, <i>CYP7B1</i>, and <i>ZFYVE26</i> were identified, respectively. Intra and interfamilial clinical variability were observed among affected individuals. Mutations in <i>CYP7B1</i> and <i>ZFYVE26</i> are relatively common causes of HSP and associated with SPG5A and SPG15, respectively. However, mutations in <i>ENTPD1</i> are related to SPG64 which is an ultra-rare form of HSP. The research affirmed more complexities of phenotypic manifestations and allelic heterogeneity in HSP. Due to these complexities, it is not feasible to show a clear phenotype-genotype correlation in HSP cases. Identification of more families with mutations in HSP-causing genes may help the establishment of this correlation, further understanding of the molecular basis of the disease, and would provide an opportunity for genetic-counseling in these families.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"35 2","pages":"84-94"},"PeriodicalIF":1.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2021.1895146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25520610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compound heterozygous <i>KCTD7</i> variants in progressive myoclonus epilepsy.","authors":"Elizabeth A Burke,&nbsp;Morgan Sturgeon,&nbsp;Diane B Zastrow,&nbsp;Liliana Fernandez,&nbsp;Cameron Prybol,&nbsp;Shruti Marwaha,&nbsp;Edward P Frothingham,&nbsp;Patricia A Ward,&nbsp;Christine M Eng,&nbsp;Laure Fresard,&nbsp;Stephen B Montgomery,&nbsp;Gregory M Enns,&nbsp;Paul G Fisher,&nbsp;Lynne A Wolfe,&nbsp;Brian Harding,&nbsp;Blake Carrington,&nbsp;Kevin Bishop,&nbsp;Raman Sood,&nbsp;Yan Huang,&nbsp;Abdel Elkahloun,&nbsp;Camilo Toro,&nbsp;Alexander G Bassuk,&nbsp;Matthew T Wheeler,&nbsp;Thomas C Markello,&nbsp;William A Gahl,&nbsp;May Christine V Malicdan","doi":"10.1080/01677063.2021.1892095","DOIUrl":"https://doi.org/10.1080/01677063.2021.1892095","url":null,"abstract":"<p><p>KCTD7 is a member of the potassium channel tetramerization domain-containing protein family and has been associated with progressive myoclonic epilepsy (PME), characterized by myoclonus, epilepsy, and neurological deterioration. Here we report four affected individuals from two unrelated families in which we identified <i>KCTD7</i> compound heterozygous single nucleotide variants through exome sequencing. RNAseq was used to detect a non-annotated splicing junction created by a synonymous variant in the second family. Whole-cell patch-clamp analysis of neuroblastoma cells overexpressing the patients' variant alleles demonstrated aberrant potassium regulation. While all four patients experienced many of the common clinical features of PME, they also showed variable phenotypes not previously reported, including dysautonomia, brain pathology findings including a significantly reduced thalamus, and the lack of myoclonic seizures. To gain further insight into the pathogenesis of the disorder, zinc finger nucleases were used to generate <i>kctd7</i> knockout zebrafish. <i>Kctd7</i> homozygous mutants showed global dysregulation of gene expression and increased transcription of <i>c-fos</i>, which has previously been correlated with seizure activity in animal models. Together these findings expand the known phenotypic spectrum of <i>KCTD7</i>-associated PME, report a new animal model for future studies, and contribute valuable insights into the disease.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"35 2","pages":"74-83"},"PeriodicalIF":1.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2021.1892095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38967602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rapid molecular diagnostic method for spinal muscular atrophy.","authors":"Kai-Chen Wang,&nbsp;Chiao-Yuan Fang,&nbsp;Chi-Chang Chang,&nbsp;Chien-Kuan Chiang,&nbsp;Yi-Wen Chen","doi":"10.1080/01677063.2020.1853721","DOIUrl":"https://doi.org/10.1080/01677063.2020.1853721","url":null,"abstract":"<p><p>Spinal muscular atrophy (SMA) is a common autosomal recessive disorder which has been considered as the second common cause of infant death, with an estimated prevalence of 1 in 10,000 live births. The disorder is caused by survival motor neuron 1 gene (<i>SMN1</i>) deficiency leading to limb weakness, difficult swallowing and abnormal breathing. Here, a fast and accurate method for SMA detection has been developed. Genomic DNA sample collected from whole blood, amniotic fluid, or dried blood spots can be analysed by using the Clarity™ Digital PCR (dPCR) System for determining the copy numbers of <i>SMN1</i> and <i>SMN2</i> genes. Two hundred and fourteen clinical samples determined by qPCR-based method were enrolled and used to establish the cut-off ranges for unaffected individual, SMA carrier and SMA patient categories. After setting the cut-off range for each group, 12 samples were analyzed by both dPCR-based method and MLPA (multiplex ligation-dependent probe amplification), the current testing golden standard for SMA, and 100% concordant results between the two testing methods were performed. CSB SMA Detection Kit combined with dPCR platform provides a robust and precise approach to distinguish unaffected individuals, SMA carrier and SMA patients. This rapid molecular diagnostic method can be adapted to pre-pregnancy eugenics inspection, prenatal testing as well as newborns screening and help physicians or genetic counselors to improve population SMA incidence.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"35 1","pages":"29-32"},"PeriodicalIF":1.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2020.1853721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38725268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Biallelic ZNF335</i> mutations cause basal ganglia abnormality with progressive cerebral/cerebellar atrophy.","authors":"Ahmet Okay Caglayan,&nbsp;Kourosh Yaghouti,&nbsp;Tanyel Kockaya,&nbsp;Demet Kemer,&nbsp;Tufan Cankaya,&nbsp;Najim Ameziane,&nbsp;Ozgur Cogulu,&nbsp;Mahmut Coker,&nbsp;Cengiz Yalcinkaya","doi":"10.1080/01677063.2020.1833006","DOIUrl":"https://doi.org/10.1080/01677063.2020.1833006","url":null,"abstract":"<p><p>To date, less than 10 pedigrees have been reported with <i>ZNF335</i> mutations since it was discovered in 2012 and little is known about ZNF335-related clinical spectrum. We describe a 12 years old male patient who is only child of nonconsanguineous Turkish parents. Trio whole genome sequencing identified previously unreported compound heterozygous variants in <i>ZNF335</i>, namely, c.3889T > A p.(Ser1297Thr) and c.758G > A p.(Arg253Gln) where transmitted by his father and mother, respectively. Patient' magnetic resonance imaging findings were overlapping to those observed in the previous cases with <i>ZNF335</i> mutations. Here we report the oldest patient with biallelic <i>ZNF335</i> mutations. We recommend screening for ZNF335 defects in patients with basal ganglia anomaly, secondary white matter abnormalities and microcephaly.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"35 1","pages":"23-28"},"PeriodicalIF":1.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2020.1833006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38627967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of whole genome sequenced cases and controls shows that the association of variants in <i>TOMM40</i>, <i>BCAM</i>, <i>NECTIN2</i> and <i>APOC1</i> with late onset Alzheimer's disease is driven by linkage disequilibrium with <i>APOE</i> ε2/ε3/ε4 alleles.","authors":"David Curtis","doi":"10.1080/01677063.2020.1866569","DOIUrl":"10.1080/01677063.2020.1866569","url":null,"abstract":"<p><p>Variants in <i>APOE</i> are associated with risk of late onset Alzheimer's disease (LOAD) but the magnitude of the effect has been reported to vary across ancestries. Also, other variants in the region have been reported to show association though it has been unclear whether this was secondary to their linkage disequilibrium with the <i>APOE</i> variants rs429358 and rs7412. Previous analyses of exome-sequenced samples have identified other genes in which rare variants impact risk of disease. In this study 2000 whole genome sequenced cases and controls with different ancestries were subjected to gene-based weighted burden analysis to identify risk genes. Additionally, individual variants in the <i>APOE</i> region were tested for association with LOAD. When using the <i>APOE</i> variants as covariates no individual genes showed statistically significant evidence for association after Bonferroni correction for multiple testing, which may well be a consequence of the modest sample size. Likewise, for those variants initially showing evidence of association with LOAD incorporating the <i>APOE</i> variants as covariates dramatically reduced the strength of association. These results demonstrate that the differential association of <i>APOE</i> across ancestries does not appear to be driven by another variant in the region. It seems likely that no other genes in the region have a direct effect on LOAD risk.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"35 2","pages":"59-66"},"PeriodicalIF":1.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38977590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of GAL4 drivers that mark distinct cell types and regions in the <i>Drosophila</i> adult gut.","authors":"Seung Yeon Lim,&nbsp;Hyejin You,&nbsp;Jinhyeong Lee,&nbsp;Jaejin Lee,&nbsp;Yoojin Lee,&nbsp;Kyung-Ah Lee,&nbsp;Boram Kim,&nbsp;Ji-Hoon Lee,&nbsp;JiHyeon Jeong,&nbsp;Sooin Jang,&nbsp;Byoungsoo Kim,&nbsp;Hyungjun Choi,&nbsp;Gayoung Hwang,&nbsp;Min Sung Choi,&nbsp;Sung-Eun Yoon,&nbsp;Jae Young Kwon,&nbsp;Won-Jae Lee,&nbsp;Young-Joon Kim,&nbsp;Greg S B Suh","doi":"10.1080/01677063.2020.1853722","DOIUrl":"https://doi.org/10.1080/01677063.2020.1853722","url":null,"abstract":"<p><p>The gastrointestinal tract in the adult <i>Drosophila</i> serves as a model system for exploring the mechanisms underlying digestion, absorption and excretion, stem cell plasticity, and inter-organ communication, particularly through the gut-brain axis. It is also useful for studying the cellular and adaptive responses to dietary changes, alterations in microbiota and immunity, and systematic and endocrine signals. Despite the various cell types and distinct regions in the gastrointestinal tract, few tools are available to target and manipulate the activity of each cell type and region, and their gene expression. Here, we report 353 GAL4 lines and several split-GAL4 lines that are expressed in enteric neurons (ENs), progenitors (ISCs and EBs), enterocytes (ECs), enteroendocrine cells (EEs), or/and other cell types that are yet to be identified in distinct regions of the gut. We had initially collected approximately 600 GAL4 lines that may be expressed in the gut based on RNA sequencing data, and then crossed them to <i>UAS-GFP</i> to perform immunohistochemistry to identify those that are expressed selectively in the gut. The cell types and regional expression patterns that are associated with the entire set of GAL4 drivers and split-GAL4 combinations are annotated online at http://kdrc.kr/index.php (K-Gut Project). This GAL4 resource can be used to target specific populations of distinct cell types in the fly gut, and therefore, should permit a more precise investigation of gut cells that regulate important biological processes.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"35 1","pages":"33-44"},"PeriodicalIF":1.9,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2020.1853722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38379238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A journey to 'tame a small metazoan organism', ^‡ seen through the artistic eyes of <i>C. elegans</i> researchers.","authors":"Eleni Gourgou, Alexandra R Willis, Sebastian Giunti, Maria J De Rosa, Amanda G Charlesworth, Mirella Hernandez Lima, Elizabeth Glater, Sonja Soo, Bianca Pereira, Kübra Akbaş, Anushka Deb, Madhushree Kamak, Mark W Moyle, Annika Traa, Aakanksha Singhvi, Surojit Sural, Eugene Jennifer Jin","doi":"10.1080/01677063.2020.1839449","DOIUrl":"10.1080/01677063.2020.1839449","url":null,"abstract":"<p><p>In the following pages, we share a collection of photos, drawings, and mixed-media creations, most of them especially made for this JoN issue, manifesting <i>C. elegans</i> researchers' affection for their model organism and the founders of the field. This is a celebration of our community's growth, flourish, spread, and bright future. Descriptions provided by the contributors, edited for space. ¹.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"34 3-4","pages":"549-560"},"PeriodicalIF":1.9,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2020.1839449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10151241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nature's gift to neuroscience.","authors":"Joy Alcedo, Yishi Jin, Douglas S Portman, Veena Prahlad, David Raizen, Georgia Rapti, X Z Shawn Xu, Yun Zhang, Chun-Fang Wu","doi":"10.1080/01677063.2020.1841760","DOIUrl":"10.1080/01677063.2020.1841760","url":null,"abstract":"","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"34 3-4","pages":"223-224"},"PeriodicalIF":1.9,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2020.1841760","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9762051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Studying neural circuits of decision-making in <i>Drosophila</i> larva.","authors":"Tihana Jovanic","doi":"10.1080/01677063.2020.1719407","DOIUrl":"https://doi.org/10.1080/01677063.2020.1719407","url":null,"abstract":"<p><p>To study neural circuits underlying decisions, the model organism used for that purpose has to be simple enough to be able to dissect the circuitry neuron by neuron across the nervous system and in the same time complex enough to be able to perform different types of decisions. Here, I lay out the case: (1) that <i>Drosophila</i> larva is an advantageous model system that balances well these two requirements and (2) the insights gained from this model, assuming that circuit principles may be shared across species, can be used to advance our knowledge of neural circuit implementation of decision-making in general, including in more complex brains.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"34 1","pages":"162-170"},"PeriodicalIF":1.9,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/01677063.2020.1719407","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37639667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}