Genomics and Informatics最新文献_第5页

Analysis of gene expression profiles to study malaria vaccine dose efficacy and immune response modulation. 基因表达谱分析研究疟疾疫苗剂量有效性和免疫反应调节。

Genomics and Informatics Pub Date : 2022-09-01 Epub Date: 2022-09-30 DOI: 10.5808/gi.22049

Supantha Dey, Harpreet Kaur, Mohit Mazumder, Elia Brodsky

{"title":"Analysis of gene expression profiles to study malaria vaccine dose efficacy and immune response modulation.","authors":"Supantha Dey, Harpreet Kaur, Mohit Mazumder, Elia Brodsky","doi":"10.5808/gi.22049","DOIUrl":"https://doi.org/10.5808/gi.22049","url":null,"abstract":"Malaria is a life-threatening disease, and Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of each dose of vaccine on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on samples collected from the Gene Expression Omnibus datasets. Subsequently, differential gene expression analysis using edgeR revealed the significantly (false discovery rate < 0.005) 158 downregulated and 61 upregulated genes between control vs. controlled human malaria infection samples. Further, enrichment analysis of significant genes delineated the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc., genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight into the dual role of cytokine responses in malaria pathogenesis. The variations in their expression patterns after various doses of vaccination are linked to the protection as it decreases the severe inflammatory effects in malaria patients. This study will be helpful in designing a better vaccine against malaria and understanding the functions of cytokine response as well.","PeriodicalId":36591,"journal":{"name":"Genomics and Informatics","volume":" ","pages":"e32"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33511401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of missing levels of nesting in multilevel analysis. 多层分析中缺少嵌套层的影响。

Genomics and Informatics Pub Date : 2022-09-01 Epub Date: 2022-09-30 DOI: 10.5808/gi.22052

Seho Park, Yujin Chung

{"title":"The effect of missing levels of nesting in multilevel analysis.","authors":"Seho Park, Yujin Chung","doi":"10.5808/gi.22052","DOIUrl":"https://doi.org/10.5808/gi.22052","url":null,"abstract":"Multilevel analysis is an appropriate and powerful tool for analyzing hierarchical structure data widely applied from public health to genomic data. In practice, however, we may lose the information on multiple nesting levels in the multilevel analysis since data may fail to capture all levels of hierarchy, or the top or intermediate levels of hierarchy are ignored in the analysis. In this study, we consider a multilevel linear mixed effect model (LMM) with single imputation that can involve all data hierarchy levels in the presence of missing top or intermediate-level clusters. We evaluate and compare the performance of a multilevel LMM with single imputation with other models ignoring the data hierarchy or missing intermediate-level clusters. To this end, we applied a multilevel LMM with single imputation and other models to hierarchically structured cohort data with some intermediate levels missing and to simulated data with various cluster sizes and missing rates of intermediate-level clusters. A thorough simulation study demonstrated that an LMM with single imputation estimates fixed coefficients and variance components of a multilevel model more accurately than other models ignoring data hierarchy or missing clusters in terms of mean squared error and coverage probability. In particular, when models ignoring data hierarchy or missing clusters were applied, the variance components of random effects were overestimated. We observed similar results from the analysis of hierarchically structured cohort data.","PeriodicalId":36591,"journal":{"name":"Genomics and Informatics","volume":" ","pages":"e34"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33511402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Viral culture, genome characterization, and mutation analysis of human influenza A virus. 人甲型流感病毒的病毒培养、基因组特征和突变分析。

Genomics and Informatics Pub Date : 2022-09-01 Epub Date: 2022-09-30 DOI: 10.5808/gi.22043

Rujittika Mungmunpuntipantip, Viroj Wiwanitkti

{"title":"Viral culture, genome characterization, and mutation analysis of human influenza A virus.","authors":"Rujittika Mungmunpuntipantip, Viroj Wiwanitkti","doi":"10.5808/gi.22043","DOIUrl":"https://doi.org/10.5808/gi.22043","url":null,"abstract":"2022 Korea Genome Organization This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons. org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Dear Editor, we found that the publication on “Genome characterization and mutation analysis of human influenza A virus in Thailand” in the journal [1] is very interesting. This study's findings indicated that 90 samples, including 44 H1N1 and 46 H3N2 viruses, were virally positive. Forty-three of these samples were successfully isolated, and 25 of those had their viral genomes entirely amplified. The genetic characterization of influenza viruses that are now in circulation is suggested as the final step in preparing for pandemic and epidemic outbreaks in the future. We all agree that the information is helpful. However, the most accurate laboratory analysis should be used to generate the results. There may be some clinical laboratory significance to the low isolatable rate in this report. The Madin-Darby canine kidney (MDCK) cells were used in the current study's methods for viral culture. According to a prior clinical investigation [2], MDCK-SIAT1 cells outperform conventional MDCK. Utilizing a better cell type for culture may aid in the virus's capacity to be isolated and provide accurate information on the molecular epidemiology of influenza A.","PeriodicalId":36591,"journal":{"name":"Genomics and Informatics","volume":" ","pages":"e37"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33511405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mining and analysis of microsatellites in human coronavirus genomes using the in-house built Java pipeline. 使用内部构建的Java管道挖掘和分析人类冠状病毒基因组中的微卫星。

Genomics and Informatics Pub Date : 2022-09-01 Epub Date: 2022-09-30 DOI: 10.5808/gi.20033

P K Bharti, Akhtar Husai

{"title":"Mining and analysis of microsatellites in human coronavirus genomes using the in-house built Java pipeline.","authors":"P K Bharti, Akhtar Husai","doi":"10.5808/gi.20033","DOIUrl":"https://doi.org/10.5808/gi.20033","url":null,"abstract":"Microsatellites or simple sequence repeats are motifs of 1 to 6 nucleotides in length present in both coding and non-coding regions of DNA. These are found widely distributed in the whole genome of prokaryotes, eukaryotes, bacteria, and viruses and are used as molecular markers in studying DNA variations, gene regulation, genetic diversity and evolutionary studies, etc. However, in vitro microsatellite identification proves to be time-consuming and expensive. Therefore, the present research has been focused on using an in-house built java pipeline to identify, analyse, design primers and find related statistics of perfect and compound microsatellites in the seven complete genome sequences of coronavirus, including the genome of coronavirus disease 2019, where the host is Homo sapiens. Based on search criteria among seven genomic sequences, it was revealed that the total number of perfect simple sequence repeats (SSRs) found to be in the range of 76 to 118 and compound SSRs from 01 to10, thus reflecting the low conversion of perfect simple sequence to compound repeats. Furthermore, the incidence of SSRs was insignificant but positively correlated with genome size (R2 = 0.45, p > 0.05), with simple sequence repeats relative abundance (R2 = 0.18, p > 0.05) and relative density (R2 = 0.23, p > 0.05). Dinucleotide repeats were the most abundant in the coding region of the genome, followed by tri, mono, and tetra. This comparative study would help us understand the evolutionary relationship, genetic diversity, and hypervariability in minimal time and cost.","PeriodicalId":36591,"journal":{"name":"Genomics and Informatics","volume":" ","pages":"e35"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33511404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A systemic study on the vulnerability and fatality of prostate cancer patients towards COVID-19 through analysis of the TMPRSS2, CXCL10 and their co-expressed genes. 通过分析TMPRSS2、CXCL10及其共表达基因，系统研究前列腺癌患者对COVID-19的易感性和致死率。

Genomics and Informatics Pub Date : 2022-09-01 Epub Date: 2022-09-30 DOI: 10.5808/gi.22012

Md Thosif Raza, Shagufta Mizan

{"title":"A systemic study on the vulnerability and fatality of prostate cancer patients towards COVID-19 through analysis of the TMPRSS2, CXCL10 and their co-expressed genes.","authors":"Md Thosif Raza, Shagufta Mizan","doi":"10.5808/gi.22012","DOIUrl":"https://doi.org/10.5808/gi.22012","url":null,"abstract":"A pandemic of respiratory disease named coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is reported prostate cancer patients are susceptible to COVID-19 infection. To understand the possible causes of prostate cancer patients' increased vulnerability and mortality from COVID-19 infection, we focused on the two most important agents, transmembrane protease serine subtype 2 (TMPRSS2) and the C-X-C motif 10 (CXCL10). When SARS-CoV-2 binds to the host cell via S protein-angiotensin-converting enzyme-2 receptor interaction, TMPRSS2 contributes in the proteolytic cleavage of the S protein, allowing the viral and cellular membranes to fuse. CXCL10 is a cytokine found in elevated level in both COVID-19 and cancer-causing cytokine storm. We discovered that TMPRSS2 and CXCL10 are overexpressed in prostate cancer and COVID-19 using the UALCAN and GEPIA2 datasets. The functional importance of TMPRSS2 and CXCL10 in prostate cancer development was then determined by analyzing the frequency of genetic changes in their amino acid sequences using the cBioPortal online portal. Finally, we used the PANTHER database to examine the pathology of the targeted genes. We observed that TMPRSS2 and CXCL10, together with their often co-expressed genes, are important in the binding activity and immune responses in prostate cancer and COVID-19 infection, respectively. Finally, we found that TMPRSS2 and CXCL10 are two putative biomarkers responsible for the increased vulnerability and fatality of prostate cancer patients to COVID-19.","PeriodicalId":36591,"journal":{"name":"Genomics and Informatics","volume":" ","pages":"e31"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33511400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Pathogenesis and prognosis of primary oral squamous cell carcinoma based on microRNAs target genes: a systems biology approach. 基于microrna靶基因的原发性口腔鳞状细胞癌的发病机制和预后:一种系统生物学方法。

Genomics and Informatics Pub Date : 2022-09-01 Epub Date: 2022-09-30 DOI: 10.5808/gi.22038

Amir Taherkhani, Shahab Shahmoradi Dehto, Shokoofeh Jamshidi, Setareh Shojaei

{"title":"Pathogenesis and prognosis of primary oral squamous cell carcinoma based on microRNAs target genes: a systems biology approach.","authors":"Amir Taherkhani, Shahab Shahmoradi Dehto, Shokoofeh Jamshidi, Setareh Shojaei","doi":"10.5808/gi.22038","DOIUrl":"https://doi.org/10.5808/gi.22038","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck malignancy, with frequent cervical lymph-node metastasis, leading to a poor prognosis in OSCC patients. The present study aimed to identify potential markers, including microRNAs (miRNAs) and genes, significantly involved in the etiology of early-stage OSCC. Additionally, the main OSCC's dysregulated Gene Ontology annotations and significant signaling pathways were identified. The dataset GSE45238 underwent multivariate statistical analysis in order to distinguish primary OSCC tissues from healthy oral epithelium. Differentially expressed miRNAs (DEMs) with the criteria of p-value < 0.001 and |Log2 fold change| > 1.585 were identified in the two groups, and subsequently, validated targets of DEMs were identified. A protein interaction map was constructed, hub genes were identified, significant modules within the network were illustrated, and significant pathways and biological processes associated with the clusters were demonstrated. Using the GEPI2 database, the hub genes' predictive function was assessed. Compared to the healthy controls, main OSCC had a total of 23 DEMs. In patients with head and neck squamous cell carcinoma (HNSCC), upregulation of CALM1, CYCS, THBS1, MYC, GATA6, and SPRED3 was strongly associated with a poor prognosis. In HNSCC patients, overexpression of PIK3R3, GIGYF1, and BCL2L11 was substantially correlated with a good prognosis. Besides, \"proteoglycans in cancer\" was the most significant pathway enriched in the primary OSCC. The present study results revealed more possible mechanisms mediating primary OSCC and may be useful in the prognosis of the patients with early-stage OSCC.","PeriodicalId":36591,"journal":{"name":"Genomics and Informatics","volume":" ","pages":"e27"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33538777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Computer-aided drug design of Azadirachta indica compounds against nervous necrosis virus by targeting grouper heat shock cognate protein 70 (GHSC70): quantum mechanics calculations and molecular dynamic simulation approaches. 以石斑鱼热休克同源蛋白70 (GHSC70)为靶点的印楝化合物抗神经坏死病毒的计算机辅助药物设计:量子力学计算和分子动力学模拟方法

Genomics and Informatics Pub Date : 2022-09-01 Epub Date: 2022-09-30 DOI: 10.5808/gi.21063

Sk Injamamul Islam, Saloa Saloa, Sarower Mahfuj, Md Jakiul Islam, Moslema Jahan Mou

{"title":"Computer-aided drug design of Azadirachta indica compounds against nervous necrosis virus by targeting grouper heat shock cognate protein 70 (GHSC70): quantum mechanics calculations and molecular dynamic simulation approaches.","authors":"Sk Injamamul Islam, Saloa Saloa, Sarower Mahfuj, Md Jakiul Islam, Moslema Jahan Mou","doi":"10.5808/gi.21063","DOIUrl":"https://doi.org/10.5808/gi.21063","url":null,"abstract":"Nervous necrosis virus (NNV) is a deadly infectious disease that affects several fish species. It has been found that the NNV utilizes grouper heat shock cognate protein 70 (GHSC70) to enter the host cell. Thus, blocking the virus entry by targeting the responsible protein can protect the fishes from disease. The main objective of the study was to evaluate the inhibitory potentiality of 70 compounds of Azadirachta indica (Neem plant) which has been reported to show potential antiviral activity against various pathogens, but activity against the NNV has not yet been reported. The binding affinity of 70 compounds was calculated against the GHSC70 with the docking and molecular dynamics (MD) simulation approaches. Both the docking and MD methods predict 4 (PubChem CID: 14492795, 10134, 5280863, and 11119228) inhibitory compounds that bind strongly with the GHSC70 protein with a binding affinity of -9.7, -9.5, -9.1, and -9.0 kcal/mol, respectively. Also, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the compounds confirmed the drug-likeness properties. As a result of the investigation, it may be inferred that Neem plant compounds may act as significant inhibitors of viral entry into the host cell. More in-vitro testing is needed to establish their effectiveness.","PeriodicalId":36591,"journal":{"name":"Genomics and Informatics","volume":" ","pages":"e33"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33511403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Whole-exome sequencing analysis in a case of primary congenital glaucoma due to the partial uniparental isodisomy. 先天性青光眼的全外显子组测序分析。

Genomics and Informatics Pub Date : 2022-09-01 Epub Date: 2022-09-30 DOI: 10.5808/gi.21044

Parisima Ghaffarian Zavarzadeh, Morteza Bonyadi, Zahra Abedi

{"title":"Whole-exome sequencing analysis in a case of primary congenital glaucoma due to the partial uniparental isodisomy.","authors":"Parisima Ghaffarian Zavarzadeh, Morteza Bonyadi, Zahra Abedi","doi":"10.5808/gi.21044","DOIUrl":"https://doi.org/10.5808/gi.21044","url":null,"abstract":"We described a clinical, laboratory, and genetic presentation of a pathogenic variant of the CYP1B1 gene through a report of a case of primary congenital glaucoma and a trio analysis of this candidate variant in the family with the sanger sequencing method and eventually completed our study with the secondary/incidental findings. This study reports a rare case of primary congenital glaucoma, an 8-year-old female child with a negative family history of glaucoma and uncontrolled intraocular pressure. This case's whole-exome sequencing data analysis presents a homozygous pathogenic single nucleotide variant in the CYP1B1 gene (NM 000104:exon3:c.G1103A:p.R368H). At the same time, this pathogenic variant was obtained as a heterozygous state in her unaffected father but not her mother. The diagnosis was made based on molecular findings of whole-exome sequencing data analysis. Therefore, the clinical reports and bioinformatics findings supported the relation between the candidate pathogenic variant and the disease. However, it should not be forgotten that primary congenital glaucoma is not peculiar to the CYP1B1 gene. Since the chance of developing autosomal recessive disorders with low allele frequency and unrelated parents is extraordinary in offspring. However, further data analysis of whole-exome sequencing and sanger sequencing method were applied to obtain the type of mutation and how it was carried to the offspring.","PeriodicalId":36591,"journal":{"name":"Genomics and Informatics","volume":" ","pages":"e28"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33538776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

The UGT1A9*22 genotype identifies a high-risk group for irinotecan toxicity among gastric cancer patients. UGT1A9*22基因型确定了胃癌患者中伊立替康毒性的高危人群。

Genomics and Informatics Pub Date : 2022-09-01 Epub Date: 2022-09-30 DOI: 10.5808/gi.22051

Choong-Kun Lee, Hong Jae Chon, Woo Sun Kwon, Hyo-Jeong Ban, Sang Cheol Kim, Hyunwook Kim, Hei-Cheul Jeung, Jimyung Chung, Sun Young Rha

{"title":"The UGT1A9*22 genotype identifies a high-risk group for irinotecan toxicity among gastric cancer patients.","authors":"Choong-Kun Lee, Hong Jae Chon, Woo Sun Kwon, Hyo-Jeong Ban, Sang Cheol Kim, Hyunwook Kim, Hei-Cheul Jeung, Jimyung Chung, Sun Young Rha","doi":"10.5808/gi.22051","DOIUrl":"https://doi.org/10.5808/gi.22051","url":null,"abstract":"Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3, and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III-IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of severe toxicity such as intense diarrhea or neutropenia.","PeriodicalId":36591,"journal":{"name":"Genomics and Informatics","volume":" ","pages":"e29"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33538778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Two novel mutations in ALDH18A1 and SPG11 gene found by whole-exome sequencing in spastic paraplegia disease patients in Iran. 通过全外显子组测序在伊朗痉挛性截瘫患者中发现ALDH18A1和SPG11基因的两个新突变

Genomics and Informatics Pub Date : 2022-09-01 Epub Date: 2022-09-30 DOI: 10.5808/gi.22030

Sajad Rafiee Komachali, Zakieh Siahpoosh, Mansoor Salehi

{"title":"Two novel mutations in ALDH18A1 and SPG11 gene found by whole-exome sequencing in spastic paraplegia disease patients in Iran.","authors":"Sajad Rafiee Komachali, Zakieh Siahpoosh, Mansoor Salehi","doi":"10.5808/gi.22030","DOIUrl":"https://doi.org/10.5808/gi.22030","url":null,"abstract":"Hereditary spastic paraplegia is a not common inherited neurological disorder with heterogeneous clinical expressions. ALDH18A1 (located on 10q24.1) gene-related spastic paraplegias (SPG9A and SPG9B) are rare metabolic disorders caused by dominant and recessive mutations that have been found recently. Autosomal recessive hereditary spastic paraplegia is a common and clinical type of familial spastic paraplegia linked to the SPG11 locus (locates on 15q21.1). There are different symptoms of spastic paraplegia, such as muscle atrophy, moderate MR, short stature, balance problem, and lower limb weakness. Our first proband involves a 45 years old man and our second proband involves a 20 years old woman both are affected by spastic paraplegia disease. Genomic DNA was extracted from the peripheral blood of the patients, their parents, and their siblings using a filter-based methodology and quantified and used for molecular analysis and sequencing. Sequencing libraries were generated using Agilent SureSelect Human All ExonV7 kit, and the qualified libraries are fed into NovaSeq 6000 Illumina sequencers. Sanger sequencing was performed by an ABI prism 3730 sequencer. Here, for the first time, we report two cases, the first one which contains likely pathogenic NM_002860: c.475C>T: p.R159X mutation of the ALDH18A1 and the second one has likely pathogenic NM_001160227.2: c.5454dupA: p.Glu1819Argfs Ter11 mutation of the SPG11 gene and also was identified by the whole-exome sequencing and confirmed by Sanger sequencing. Our aim with this study was to confirm that these two novel variants are direct causes of spastic paraplegia.","PeriodicalId":36591,"journal":{"name":"Genomics and Informatics","volume":" ","pages":"e30"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33511399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0