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1
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Jafari P, Forrest M, Segal J, Wang P, Tjota MY. Pan-Cancer Molecular Biomarkers: Practical Considerations for the Surgical Pathologist. Mod Pathol 2025; 38:100752. [PMID: 40058460 DOI: 10.1016/j.modpat.2025.100752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 02/25/2025] [Accepted: 02/26/2025] [Indexed: 03/29/2025]
Abstract
Traditional anatomic pathologic classification of cancer is based on tissue of origin and morphologic and immunohistochemical characterization of the malignant cells. With the technological improvements of massively parallel or next-generation sequencing, oncogenic drivers that are shared across different tumor types are increasingly being identified and used as pan-cancer biomarkers. This approach is reflected in the growing list of Food and Drug Administration-approved tumor-agnostic therapies, including pembrolizumab in the setting of microsatellite instability and high tumor mutational burden, larotrectinib and entrectinib for solid tumors with NTRK fusions, and combined dabrafenib-trametinib for BRAF V600E-mutated neoplasms. Several other biomarkers are currently under investigation, including fibroblast growth factor receptor (FGFR), RET, and ROS1 fusions; ERBB2 amplification; and mutations in the AKT1/2/3, NF1, RAS pathway and (mitogen-activated protein kinase (MAPK) pathway. As molecular assays are increasingly incorporated into routine tumor workup, the emergence of additional pan-cancer biomarkers is likely to be a matter more of "when" than "if." In this review, we first explore some of the conceptual and technical considerations at the intersection of surgical and molecular pathology, followed by a brief overview of both established and emerging molecular pan-cancer biomarkers and their diagnostic and clinical applications.
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Affiliation(s)
- Pari Jafari
- Department of Pathology, The University of Chicago, Chicago, Illinois
| | - Megan Forrest
- Department of Pathology, The University of Chicago, Chicago, Illinois
| | - Jeremy Segal
- Department of Pathology, The University of Chicago, Chicago, Illinois
| | - Peng Wang
- Department of Pathology, The University of Chicago, Chicago, Illinois
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2
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Alhatim HA, Abdullah MNH, Jamaludin SA, Nurdin AB, Amer SA. STR profiling in a cohort of Saudi patients with acute leukemia. J Taibah Univ Med Sci 2025; 20:62-72. [PMID: 40026413 PMCID: PMC11869027 DOI: 10.1016/j.jtumed.2025.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 11/19/2024] [Accepted: 01/25/2025] [Indexed: 03/05/2025] Open
Abstract
Objective This study was aimed at characterizing whether the autosomal short tandem repeats (STRs) used in forensic identification might differ between leukemic blood samples and saliva samples. Methods Blood and saliva samples were collected from 27 patients diagnosed with acute leukemia in Riyadh City, KSA. DNA was extracted, and 15 STR loci were amplified. Results Approximately 59.3% of patients with leukemia exhibited mutations at the STR loci. Loss of heterozygosity (LOH) occurred in 40.7% of the patients at D19S433, D16S539, vWA, D13S317, TH01, FGA, and D2S1338. Microsatellite instability (MSI) was detected in 22.2% of patients at TPOX, vWA, D19S433, D16S539, and D18S51. D19S433 and D16S539 were the most affected loci, exhibiting an alteration percentage of 18.52%, followed by vWA (11.11%); in contrast, D2S1338, D18S51, and TPOX were the least affected loci, showing a mutation percentage of 3.7%. D13S317, TH01, and FGA showed moderate genetic mutation (7.41%). CSF1PO, D21S11, D3S1358, D5S818, D7S820, D8S1179, and amelogenin did not show genetic changes in all samples. The overall genetic variability between saliva and blood samples significantly differed (P < 0.001). Conclusion Our results demonstrate the potential application of forensically used STR loci in diagnosis and monitoring of patients with leukemia. Further study applying next generation sequencing technology is necessary to validate these findings and explore the clinical applications of forensically used STRs as diagnostic tools for leukemia.
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Affiliation(s)
- Husein A. Alhatim
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Malaysia
| | - Muhammad NH Abdullah
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Malaysia
| | - Suhaili A. Jamaludin
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Malaysia
| | - Armania B. Nurdin
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Malaysia
| | - Sayed A. Amer
- Department of Forensic Sciences, College of Criminal Justice, Naif Arab University for Security Sciences, KSA
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Liu J, Yu S, Lü P, Gong X, Sun M, Tang M. De novo assembly and characterization of the complete mitochondrial genome of Phellodendron amurense reveals three repeat-mediated recombination. Gene 2025; 935:149031. [PMID: 39461576 DOI: 10.1016/j.gene.2024.149031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 10/18/2024] [Accepted: 10/21/2024] [Indexed: 10/29/2024]
Abstract
Phellodendron amurense Rupr., a rare herb renowned for its medicinal and ecological significance, has remained genetically unexplored at the mitochondrial level until now. This study presents the first-ever systematic assembly and annotation of the complete mitochondrial genome of P. amurense, achieved through a hybrid strategy combining Illumina and Nanopore sequencing data. The mitochondrial genome spans 566,285 bp with a GC content of 45.51 %, structured into two circular molecules. Our comprehensive analysis identified 32 protein-coding genes (PCGs), 33 tRNA genes, and 3 rRNA genes, alongside 181 simple sequence repeats, 19 tandem repeats, and 310 dispersed repeats. Notably, multiple genome conformations were predicted due to repeat-mediated homologous recombination. Additionally, we assembled the chloroplast genome, identifying 21 mitochondrial plastid sequences that provide insights into organelle genome interactions. A total of 380 RNA-editing sites within the mitochondrial PCGs were predicted, enhancing our understanding of gene regulation and function. Phylogenetic analysis using mitochondrial PCGs from 30 species revealed evolutionary relationships, confirming the homology between P. amurense and Citrus species. This foundational study offers a valuable genetic resource for the Rutaceae family, facilitating further research into genetic evolution and molecular diversity in plant mitochondrial genomes.
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Affiliation(s)
- Junlin Liu
- School of Life Sciences, Jiangsu University, Zhenjiang 212013, Jiangsu, China
| | - Shaoshuai Yu
- Department of Pharmacy, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China
| | - Peng Lü
- School of Life Sciences, Jiangsu University, Zhenjiang 212013, Jiangsu, China
| | - Xun Gong
- Department of Rheumatology & Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, China
| | - Mengmeng Sun
- Changchun University of Chinese Medicine, Changchun 130117, Jilin, China
| | - Min Tang
- School of Life Sciences, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
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4
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Du L, Chen J, Sun D, Zhao K, Zeng Q, Yang N. Krait2: a versatile software for microsatellite investigation, visualization and marker development. BMC Genomics 2025; 26:72. [PMID: 39863857 PMCID: PMC11762079 DOI: 10.1186/s12864-025-11252-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 01/16/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Microsatellites are highly polymorphic repeat sequences ubiquitously interspersed throughout almost all genomes which are widely used as powerful molecular markers in diverse fields. Microsatellite expansions play pivotal roles in gene expression regulation and are implicated in various neurological diseases and cancers. Although much effort has been devoted to developing efficient tools for microsatellite identification, there is still a lack of a powerful tool for large-scale microsatellite analysis. RESULTS We present Krait2, a user-friendly graphical tool for investigating perfect, imperfect and compound microsatellites from FASTA and FASTQ formatted genomic datasets. Krait2 not only provides features such as primer design, repeat filtering, repeat annotation and statistical analysis, but also offers various output formats to support customized downstream analysis. Moreover, it has capability of analyzing multiple genomes simultaneously and conducting comparative analysis. CONCLUSIONS Krait2 is a versatile and easy-to-use software for both novices and experts to identify and analyze microsatellites. The installer and source code are available at https://github.com/lmdu/krait2 .
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Affiliation(s)
- Lianming Du
- Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China.
| | - Jiahao Chen
- Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China
| | - Dalin Sun
- Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China
| | - Kelei Zhao
- Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China
| | - Qianglin Zeng
- Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China
| | - Nan Yang
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province and Ministry of Education, Southwest Minzu University, Chengdu, 610225, China.
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5
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Tesi N, Salazar A, Zhang Y, van der Lee S, Hulsman M, Knoop L, Wijesekera S, Krizova J, Schneider AF, Pennings M, Sleegers K, Kamsteeg EJ, Reinders M, Holstege H. Characterizing tandem repeat complexities across long-read sequencing platforms with TREAT and otter. Genome Res 2024; 34:1942-1953. [PMID: 39406499 DOI: 10.1101/gr.279351.124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 10/03/2024] [Indexed: 11/09/2024]
Abstract
Tandem repeats (TRs) play important roles in genomic variation and disease risk in humans. Long-read sequencing allows for the accurate characterization of TRs; however, the underlying bioinformatics perspectives remain challenging. We present otter and TREAT: otter is a fast targeted local assembler, cross-compatible across different sequencing platforms. It is integrated in TREAT, an end-to-end workflow for TR characterization, visualization, and analysis across multiple genomes. In a comparison with existing tools based on long-read sequencing data from both Oxford Nanopore Technology (ONT, Simplex and Duplex) and Pacific Bioscience (PacBio, Sequel II and Revio), otter and TREAT achieve state-of-the-art genotyping and motif characterization accuracy. Applied to clinically relevant TRs, TREAT/otter significantly identify individuals with pathogenic TR expansions. When applied to a case-control setting, we replicate previously reported associations of TRs with Alzheimer's disease, including those near or within APOC1 (P = 2.63 × 10-9), SPI1 (P = 6.5 × 10-3), and ABCA7 (P = 0.04) genes. Finally, we use TREAT/otter to systematically evaluate potential biases when genotyping TRs using diverse ONT and PacBio long-read sequencing data sets. We show that, in rare cases (0.06%), long-read sequencing from coverage drops in TRs, including the disease-associated TRs in ABCA7 and RFC1 genes. Such coverage drops can lead to TR misgenotyping, hampering the accurate characterization of TR alleles. Taken together, our tools can accurately genotype TRs across different sequencing technologies and with minimal requirements, allowing end-to-end analysis and comparisons of TRs in human genomes, with broad applications in research and clinical fields.
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Affiliation(s)
- Niccoló Tesi
- Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands;
- Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
- Delft Bioinformatics Lab, Delft University of Technology, 2628CD Delft, The Netherlands
| | - Alex Salazar
- Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
| | - Yaran Zhang
- Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
| | - Sven van der Lee
- Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
- Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
| | - Marc Hulsman
- Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
- Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
- Delft Bioinformatics Lab, Delft University of Technology, 2628CD Delft, The Netherlands
| | - Lydian Knoop
- Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
| | - Sanduni Wijesekera
- Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
| | - Jana Krizova
- Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
| | - Anne-Fleur Schneider
- Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
| | - Maartje Pennings
- Department of Genome Diagnostics, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands
| | - Kristel Sleegers
- Complex Genetics of Alzheimer's Disease Group, Antwerp Center for Molecular Neurology, VIB, Antwerp B-2650, Belgium
| | - Erik-Jan Kamsteeg
- Department of Genome Diagnostics, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands
| | - Marcel Reinders
- Delft Bioinformatics Lab, Delft University of Technology, 2628CD Delft, The Netherlands
| | - Henne Holstege
- Section Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
- Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081HV Amsterdam, The Netherlands
- Delft Bioinformatics Lab, Delft University of Technology, 2628CD Delft, The Netherlands
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Geng R, Xu J, Jiang J, Cheng Z, Sun M, Xia N, Gao J. Identification of New Cultivar and Different Provenances of Dendrocalamus brandisii (Poaceae: Bambusoideae) Using Simple Sequence Repeats Developed from the Whole Genome. PLANTS (BASEL, SWITZERLAND) 2024; 13:2910. [PMID: 39458856 PMCID: PMC11511551 DOI: 10.3390/plants13202910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/10/2024] [Accepted: 10/14/2024] [Indexed: 10/28/2024]
Abstract
Dendrocalamus brandisii is a high-quality bamboo species that can be used for both bamboo shoots and wood. The nutritional components and flavors of D. brandisii vary from different geographical provenances. However, the unique biological characteristics of bamboo make morphological classification methods unsuitable for distinguishing them. Although the new cultivar 'Manxie No.1' has significant differences in the branch characteristics and the color of shoot sheaths compared to the D. brandisii, it still lacks precise genetic information at the molecular level. This study identified 231,789 microsatellite markers based on the whole genome of D. brandisii and analyzed their type composition and distribution on chromosomes in detail. Then, using TP-M13-SSR fluorescence-labeling technology, 34 pairs of polymorphic primers were screened to identify the new cultivar 'Manxie No.1' and 11 different geographical provenances of D. brandisii. We also constructed DNA fingerprinting profiles for them. At the same time, we mapped six polymorphic SSRs to the gene of D. brandisii, among which SSR673 was mapped to DhB10G011540, which is related to plant immunity. The specific markers selected in this study can rapidly identify the provenances and the new cultivar of D. brandisii and help explore candidate genes related to some important traits.
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Affiliation(s)
- Ruiman Geng
- Key Laboratory of National Forestry and Grassland Administration/Beijing for Bamboo & Rattan Science and Technology, International Center for Bamboo and Rattan, Beijing 100102, China; (R.G.); (J.X.); (J.J.); (Z.C.)
| | - Junlei Xu
- Key Laboratory of National Forestry and Grassland Administration/Beijing for Bamboo & Rattan Science and Technology, International Center for Bamboo and Rattan, Beijing 100102, China; (R.G.); (J.X.); (J.J.); (Z.C.)
| | - Jutang Jiang
- Key Laboratory of National Forestry and Grassland Administration/Beijing for Bamboo & Rattan Science and Technology, International Center for Bamboo and Rattan, Beijing 100102, China; (R.G.); (J.X.); (J.J.); (Z.C.)
| | - Zhanchao Cheng
- Key Laboratory of National Forestry and Grassland Administration/Beijing for Bamboo & Rattan Science and Technology, International Center for Bamboo and Rattan, Beijing 100102, China; (R.G.); (J.X.); (J.J.); (Z.C.)
| | - Maosheng Sun
- Institute of Bamboo and Rattan, Southwest Forestry University, Kunming 650224, China;
| | - Nianhe Xia
- South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China;
| | - Jian Gao
- Key Laboratory of National Forestry and Grassland Administration/Beijing for Bamboo & Rattan Science and Technology, International Center for Bamboo and Rattan, Beijing 100102, China; (R.G.); (J.X.); (J.J.); (Z.C.)
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7
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Xia Y, Li D, Chen T, Pan S, Huang H, Zhang W, Liang Y, Fu Y, Peng Z, Zhang H, Zhang L, Peng S, Shi R, He X, Zhou S, Jiao W, Zhao X, Wu X, Zhou L, Zhou J, Ouyang Q, Tian Y, Jiang X, Zhou Y, Tang S, Shen J, Ohshima K, Tan Z. Microsatellite density landscapes illustrate short tandem repeats aggregation in the complete reference human genome. BMC Genomics 2024; 25:960. [PMID: 39402450 PMCID: PMC11477012 DOI: 10.1186/s12864-024-10843-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 09/26/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Microsatellites are increasingly realized to have biological significance in human genome and health in past decades, the assembled complete reference sequence of human genome T2T-CHM13 brought great help for a comprehensive study of short tandem repeats in the human genome. RESULTS Microsatellites density landscapes of all 24 chromosomes were built here for the first complete reference sequence of human genome T2T-CHM13. These landscapes showed that short tandem repeats (STRs) are prone to aggregate characteristically to form a large number of STRs density peaks. We classified 8,823 High Microsatellites Density Peaks (HMDPs), 35,257 Middle Microsatellites Density Peaks (MMDPs) and 199, 649 Low Microsatellites Density Peaks (LMDPs) on the 24 chromosomes; and also classified the motif types of every microsatellites density peak. These STRs density aggregation peaks are mainly composing of a single motif, and AT is the most dominant motif, followed by AATGG and CCATT motifs. And 514 genomic regions were characterized by microsatellite density feature in the full T2T-CHM13 genome. CONCLUSIONS These landscape maps exhibited that microsatellites aggregate in many genomic positions to form a large number of microsatellite density peaks with composing of mainly single motif type in the complete reference genome, indicating that the local microsatellites density varies enormously along the every chromosome of T2T-CHM13.
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Affiliation(s)
- Yun Xia
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Douyue Li
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Tingyi Chen
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Saichao Pan
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Hanrou Huang
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Wenxiang Zhang
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Yulin Liang
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Yongzhuo Fu
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Zhuli Peng
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Hongxi Zhang
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Liang Zhang
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Shan Peng
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Ruixue Shi
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Xingxin He
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Siqian Zhou
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Weili Jiao
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Xiangyan Zhao
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Xiaolong Wu
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Lan Zhou
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Jingyu Zhou
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Qingjian Ouyang
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - You Tian
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Xiaoping Jiang
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Yi Zhou
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Shiying Tang
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | - Junxiong Shen
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China
| | | | - Zhongyang Tan
- Bioinformatic Center, College of Biology, Hunan University, Lushan Road (S), Yuelu District, Changsha, 410082, China.
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Paul B, Siddaramappa S. Comparative analysis of the diversity of trinucleotide repeats in bacterial genomes. Genome 2024; 67:281-291. [PMID: 38593473 DOI: 10.1139/gen-2023-0097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
The human gut is the most favorable niche for microbial populations, and few studies have explored the possibilities of horizontal gene transfer between host and pathogen. Trinucleotide repeat (TNR) expansion in humans can cause more than 40 neurodegenerative diseases. Further, TNRs are a type of microsatellite that resides on coding regions can contribute to the synthesis of homopolymeric amino acids. Hence, the present study aims to estimate the occurrence and diversity of TNRs in bacterial genomes available in the NCBI Genome database. Genome-wide analyses revealed that several bacterial genomes contain different types of uninterrupted TNRs. It was found that TNRs are abundant in the genomes of Alcaligenes faecalis, Mycoplasma gallisepticum, Mycoplasma genitalium, Sorangium cellulosum, and Thermus thermophilus. Interestingly, the genome of Bacillus thuringiensis strain YBT-1518 contained 169 uninterrupted ATT repeats. The genome of Leclercia adecarboxylata had 46 uninterrupted CAG repeats, which potentially translate into polyglutamine. In some instances, the TNRs were present in genes that potentially encode essential functions. Similar occurrences in human genes are known to cause genetic disorders. Further analysis of the occurrence of TNRs in bacterial genomes is likely to provide a better understanding of mismatch repair, genetic disorders, host-pathogen interaction, and homopolymeric amino acids.
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Affiliation(s)
- Bobby Paul
- Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Shivakumara Siddaramappa
- Institute of Bioinformatics and Applied Biotechnology, Biotech Park, Electronic City, Bengaluru 560100, Karnataka, India
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9
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Choi JW, Lee JO, Lee S. Detecting microsatellite instability by length comparison of microsatellites in the 3' untranslated region with RNA-seq. Brief Bioinform 2024; 25:bbae423. [PMID: 39210504 PMCID: PMC11361843 DOI: 10.1093/bib/bbae423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 07/30/2024] [Accepted: 08/09/2024] [Indexed: 09/04/2024] Open
Abstract
Microsatellite instability (MSI), a phenomenon caused by deoxyribonucleic acid (DNA) mismatch repair system deficiencies, is an important biomarker in cancer research and clinical diagnostics. MSI detection often involves next-generation sequencing data, with many studies focusing on DNA. Here, we introduce a novel approach by measuring microsatellite lengths directly from ribonucleic acid sequencing (RNA-seq) data and comparing its distribution to detect MSI. Our findings reveal distinct instability patterns between MSI-high (MSI-H) and microsatellite stable samples, indicating the efficacy of RNA-based MSI detection. Additionally, microsatellites in the 3'-untranslated regions showed the greatest predictive value for MSI detection. Notably, this efficacy extends to detecting MSI-H samples even in tumors not commonly associated with MSI. Our approach highlights the utility of RNA-seq data in MSI detection, facilitating more precise diagnostics through the integration of various biological data.
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Affiliation(s)
- Jin-Wook Choi
- Department of Health Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, 08826 Seoul, Republic of Korea
| | - Jin-Ok Lee
- Department of Health Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, 08826 Seoul, Republic of Korea
| | - Sejoon Lee
- Department of Health Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, 08826 Seoul, Republic of Korea
- Department of Pathology and Translational Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173beon-gil, Bundang-gu, 13620 Seongnam, Republic of Korea
- Precision Medicine Center, Seoul National University Bundang Hospital, 82 Gumi-ro, Bundang-gu, 13620 Seongnam, Republic of Korea
- Department of Genomic Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, Bundang-gu, 13620 Seongnam, Republic of Korea
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10
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Anthony H, Seoighe C. Performance assessment of computational tools to detect microsatellite instability. Brief Bioinform 2024; 25:bbae390. [PMID: 39129364 PMCID: PMC11317526 DOI: 10.1093/bib/bbae390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 06/26/2024] [Accepted: 07/25/2024] [Indexed: 08/13/2024] Open
Abstract
Microsatellite instability (MSI) is a phenomenon seen in several cancer types, which can be used as a biomarker to help guide immune checkpoint inhibitor treatment. To facilitate this, researchers have developed computational tools to categorize samples as having high microsatellite instability, or as being microsatellite stable using next-generation sequencing data. Most of these tools were published with unclear scope and usage, and they have yet to be independently benchmarked. To address these issues, we assessed the performance of eight leading MSI tools across several unique datasets that encompass a wide variety of sequencing methods. While we were able to replicate the original findings of each tool on whole exome sequencing data, most tools had worse receiver operating characteristic and precision-recall area under the curve values on whole genome sequencing data. We also found that they lacked agreement with one another and with commercial MSI software on gene panel data, and that optimal threshold cut-offs vary by sequencing type. Lastly, we tested tools made specifically for RNA sequencing data and found they were outperformed by tools designed for use with DNA sequencing data. Out of all, two tools (MSIsensor2, MANTIS) performed well across nearly all datasets, but when all datasets were combined, their precision decreased. Our results caution that MSI tools can have much lower performance on datasets other than those on which they were originally evaluated, and in the case of RNA sequencing tools, can even perform poorly on the type of data for which they were created.
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Affiliation(s)
- Harrison Anthony
- School of Mathematical and Statistical Sciences, University of Galway, Galway H91 TK33, Ireland
- The SFI Centre for Research Training in Genomics Data Science, Galway D02 FX65, Ireland
| | - Cathal Seoighe
- School of Mathematical and Statistical Sciences, University of Galway, Galway H91 TK33, Ireland
- The SFI Centre for Research Training in Genomics Data Science, Galway D02 FX65, Ireland
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11
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Mokveld T, Dolzhenko E, Dashnow H, Nicholas TJ, Sasani T, van der Sanden B, Jadhav B, Pedersen B, Kronenberg Z, Tucci A, Sharp AJ, Quinlan AR, Gilissen C, Hoischen A, Eberle MA. TRGT-denovo: accurate detection of de novo tandem repeat mutations. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.07.16.600745. [PMID: 39071386 PMCID: PMC11275785 DOI: 10.1101/2024.07.16.600745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
Abstract
Motivation Identifying de novo tandem repeat (TR) mutations on a genome-wide scale is essential for understanding genetic variability and its implications in rare diseases. While PacBio HiFi sequencing data enhances the accessibility of the genome's TR regions for genotyping, simple de novo calling strategies often generate an excess of likely false positives, which can obscure true positive findings, particularly as the number of surveyed genomic regions increases. Results We developed TRGT-denovo, a computational method designed to accurately identify all types of de novo TR mutations-including expansions, contractions, and compositional changes-within family trios. TRGT-denovo directly interrogates read evidence, allowing for the detection of subtle variations often overlooked in variant call format (VCF) files. TRGT-denovo improves the precision and specificity of de novo mutation (DNM) identification, reducing the number of de novo candidates by an order of magnitude compared to genotype-based approaches. In our experiments involving eight rare disease trios previously studiedTRGT-denovo correctly reclassified all false positive DNM candidates as true negatives. Using an expanded repeat catalog, it identified new candidates, of which 95% (19/20) were experimentally validated, demonstrating its effectiveness in minimizing likely false positives while maintaining high sensitivity for true discoveries. Availability and implementation Built in Rust, TRGT-denovo is available as source code and a pre-compiled Linux binary along with a user guide at: https://github.com/PacificBiosciences/trgt-denovo.
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Affiliation(s)
| | | | | | | | - T Sasani
- Univ. of Utah, Salt Lake City, UT
| | - B van der Sanden
- Department of Human Genetics, Research Institute for Medical Innovation, Radboud university medical center, Nijmegen, the Netherlands
| | - B Jadhav
- Icahn School of Medicine at Mount Sinai, New York, NY
| | | | | | - A Tucci
- Genomics England, London, UK
| | - A J Sharp
- Icahn School of Medicine at Mount Sinai, New York, NY
| | | | - C Gilissen
- Department of Human Genetics, Research Institute for Medical Innovation, Radboud university medical center, Nijmegen, the Netherlands
| | - A Hoischen
- Department of Human Genetics, Research Institute for Medical Innovation, Radboud university medical center, Nijmegen, the Netherlands
- Department of Internal Medicine, Radboud Expertise Center for Immunodeficiency and Autoinflammation and Radboud Center for Infectious Disease (RCI), Radboud university medical center, Nijmegen, the Netherlands
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12
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Kim JH, Koh IG, Lee H, Lee GH, Song DY, Kim SW, Kim Y, Han JH, Bong G, Lee J, Byun H, Son JH, Kim YR, Lee Y, Kim JJ, Park JW, Kim IB, Choi JK, Jang JH, Trost B, Lee J, Kim E, Yoo HJ, An JY. Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder. Psychiatry Clin Neurosci 2024; 78:405-415. [PMID: 38751214 PMCID: PMC11488627 DOI: 10.1111/pcn.13676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 02/14/2024] [Accepted: 04/15/2024] [Indexed: 07/06/2024]
Abstract
AIM Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.
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Affiliation(s)
- Jae Hyun Kim
- Department of Integrated Biomedical and Life Science, Korea University, Seoul, Republic of Korea
- L-HOPE Program for Community-Based Total Learning Health Systems, Korea University, Seoul, Republic of Korea
| | - In Gyeong Koh
- Department of Integrated Biomedical and Life Science, Korea University, Seoul, Republic of Korea
- L-HOPE Program for Community-Based Total Learning Health Systems, Korea University, Seoul, Republic of Korea
| | - Hyeji Lee
- Department of Integrated Biomedical and Life Science, Korea University, Seoul, Republic of Korea
- L-HOPE Program for Community-Based Total Learning Health Systems, Korea University, Seoul, Republic of Korea
| | - Gang-Hee Lee
- Department of Integrated Biomedical and Life Science, Korea University, Seoul, Republic of Korea
- L-HOPE Program for Community-Based Total Learning Health Systems, Korea University, Seoul, Republic of Korea
| | - Da-Yea Song
- Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Soo-Whee Kim
- Department of Integrated Biomedical and Life Science, Korea University, Seoul, Republic of Korea
- L-HOPE Program for Community-Based Total Learning Health Systems, Korea University, Seoul, Republic of Korea
| | - Yujin Kim
- Department of Integrated Biomedical and Life Science, Korea University, Seoul, Republic of Korea
- L-HOPE Program for Community-Based Total Learning Health Systems, Korea University, Seoul, Republic of Korea
| | - Jae Hyun Han
- Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Psychiatry, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - Guiyoung Bong
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeewon Lee
- Department of Psychiatry, Soonchunhyang University College of Medicine, Asan, Republic of Korea
| | - Heejung Byun
- Department of Neuropsychiatry, Seoul Metropolitan Children's Hospital, Seoul, Republic of Korea
| | - Ji Hyun Son
- Department of Neuropsychiatry, Seoul Metropolitan Children's Hospital, Seoul, Republic of Korea
| | - Ye Rim Kim
- Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoojeong Lee
- Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Justine Jaewon Kim
- Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jung Woo Park
- Center for Biomedical Computing, Division of National Supercomputing, Korea Institute of Science and Technology Information, Daejeon, Republic of Korea
| | - Il Bin Kim
- Department of Psychiatry, Hanyang University Guri Hospital, Guri, Republic of Korea
| | - Jung Kyoon Choi
- Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Ja-Hyun Jang
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Brett Trost
- Molecular Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada
- Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Junehawk Lee
- Center for Biomedical Computing, Division of National Supercomputing, Korea Institute of Science and Technology Information, Daejeon, Republic of Korea
| | - Eunjoon Kim
- Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, Republic of Korea
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Hee Jeong Yoo
- Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Joon-Yong An
- Department of Integrated Biomedical and Life Science, Korea University, Seoul, Republic of Korea
- L-HOPE Program for Community-Based Total Learning Health Systems, Korea University, Seoul, Republic of Korea
- School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul, Republic of Korea
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13
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Trajkovski M, Pastore A, Plavec J. Dimeric structures of DNA ATTTC repeats promoted by divalent cations. Nucleic Acids Res 2024; 52:1591-1601. [PMID: 38296828 PMCID: PMC10899783 DOI: 10.1093/nar/gkae052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 01/10/2024] [Accepted: 01/16/2024] [Indexed: 02/02/2024] Open
Abstract
Structural studies of repetitive DNA sequences may provide insights why and how certain repeat instabilities in their number and nucleotide sequence are managed or even required for normal cell physiology, while genomic variability associated with repeat expansions may also be disease-causing. The pentanucleotide ATTTC repeats occur in hundreds of genes important for various cellular processes, while their insertion and expansion in noncoding regions are associated with neurodegeneration, particularly with subtypes of spinocerebellar ataxia and familial adult myoclonic epilepsy. We describe a new striking domain-swapped DNA-DNA interaction triggered by the addition of divalent cations, including Mg2+ and Ca2+. The results of NMR characterization of d(ATTTC)3 in solution show that the oligonucleotide folds into a novel 3D architecture with two central C:C+ base pairs sandwiched between a couple of T:T base pairs. This structural element, referred to here as the TCCTzip, is characterized by intercalative hydrogen-bonding, while the nucleobase moieties are poorly stacked. The 5'- and 3'-ends of TCCTzip motif are connected by stem-loop segments characterized by A:T base pairs and stacking interactions. Insights embodied in the non-canonical DNA structure are expected to advance our understanding of why only certain pyrimidine-rich DNA repeats appear to be pathogenic, while others can occur in the human genome without any harmful consequences.
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Affiliation(s)
- Marko Trajkovski
- Slovenian NMR Centre, National Institute of Chemistry, 1000 Ljubljana, Slovenia
| | - Annalisa Pastore
- King's College London, the Maurice Wohl Clinical Neuroscience Institute, London, UK
| | - Janez Plavec
- Slovenian NMR Centre, National Institute of Chemistry, 1000 Ljubljana, Slovenia
- Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana, Slovenia
- EN-FIST, Center of Excellence, 1000 Ljubljana, Slovenia
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Crimini E, Boscolo Bielo L, Berton Giachetti PPM, Pellizzari G, Antonarelli G, Taurelli Salimbeni B, Repetto M, Belli C, Curigliano G. Beyond PD(L)-1 Blockade in Microsatellite-Instable Cancers: Current Landscape of Immune Co-Inhibitory Receptor Targeting. Cancers (Basel) 2024; 16:281. [PMID: 38254772 PMCID: PMC10813411 DOI: 10.3390/cancers16020281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 01/24/2024] Open
Abstract
High microsatellite instability (MSI-H) derives from genomic hypermutability due to deficient mismatch repair function. Colorectal (CRC) and endometrial cancers (EC) are the tumor types that more often present MSI-H. Anti-PD(L)-1 antibodies have been demonstrated to be agnostically effective in patients with MSI-H cancer, but 50-60% of them do not respond to single-agent treatment, highlighting the necessity of expanding their treatment opportunities. Ipilimumab (anti-CTLA4) is the only immune checkpoint inhibitor (ICI) non-targeting PD(L)-1 that has been approved so far by the FDA for MSI-H cancer, namely, CRC in combination with nivolumab. Anti-TIM3 antibody LY3321367 showed interesting clinical activity in combination with anti-PDL-1 antibody in patients with MSI-H cancer not previously treated with anti-PD(L)-1. In contrast, no clinical evidence is available for anti-LAG3, anti-TIGIT, anti-BTLA, anti-ICOS and anti-IDO1 antibodies in MSI-H cancers, but clinical trials are ongoing. Other immunotherapeutic strategies under study for MSI-H cancers include vaccines, systemic immunomodulators, STING agonists, PKM2 activators, T-cell immunotherapy, LAIR-1 immunosuppression reversal, IL5 superagonists, oncolytic viruses and IL12 partial agonists. In conclusion, several combination therapies of ICIs and novel strategies are emerging and may revolutionize the treatment paradigm of MSI-H patients in the future. A huge effort will be necessary to find reliable immune biomarkers to personalize therapeutical decisions.
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Affiliation(s)
- Edoardo Crimini
- Division of Early Drug Development, European Institute of Oncology, IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy (G.P.); (G.A.)
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
| | - Luca Boscolo Bielo
- Division of Early Drug Development, European Institute of Oncology, IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy (G.P.); (G.A.)
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
| | - Pier Paolo Maria Berton Giachetti
- Division of Early Drug Development, European Institute of Oncology, IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy (G.P.); (G.A.)
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
| | - Gloria Pellizzari
- Division of Early Drug Development, European Institute of Oncology, IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy (G.P.); (G.A.)
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
| | - Gabriele Antonarelli
- Division of Early Drug Development, European Institute of Oncology, IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy (G.P.); (G.A.)
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
| | - Beatrice Taurelli Salimbeni
- Division of Early Drug Development, European Institute of Oncology, IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy (G.P.); (G.A.)
| | - Matteo Repetto
- Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Carmen Belli
- Division of Early Drug Development, European Institute of Oncology, IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy (G.P.); (G.A.)
| | - Giuseppe Curigliano
- Division of Early Drug Development, European Institute of Oncology, IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy (G.P.); (G.A.)
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
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15
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Liu Z, Zheng Y. An immune-cell transcription factor tethers DNA together. Nature 2023; 624:255-256. [PMID: 38030764 DOI: 10.1038/d41586-023-03628-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2023]
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16
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Darshan K, Aggarwal R, Bashyal BM, Singh J, Saharan MS, Gurjar MS, Solanke AU. Characterization and development of transcriptome-derived novel EST-SSR markers to assess genetic diversity in Chaetomium globosum. 3 Biotech 2023; 13:379. [PMID: 37900266 PMCID: PMC10600081 DOI: 10.1007/s13205-023-03794-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 09/25/2023] [Indexed: 10/31/2023] Open
Abstract
Chaetomium globosum Kunze, an internationally recognized biocontrol fungus. It mycoparasitizes various plant pathogens and produce antifungal metabolites to suppress the growth of pathogenic fungi. Lack of detailed genome level diversity studies has delimited the development and utilization of potential C. globosum strains. The present study was taken to reveal the distribution, identification, and characterization of expressed sequence tag-simple sequence repeats (EST-SSRs) in C. globosum. RNA-Seq experiment was performed for C. globosum potential isolate Cg2 (AY429049) using Illumina HiSeq 2500. Reference-guided de novo assembly yielded 45,582 transcripts containing 27,957 unigenes. We generated a new set of 8485 EST-SSR markers distributed in 5908 unigene sequences with one SSR locus distribution density per 6.1 kb. Six distinct classes of SSR repeat motifs were identified. The most abundant were mononucleotide repeats (51.67%), followed by tri-nucleotides (36.61%). Out of 5034 EST-SSR primers, 50 primer pairs were selected and validated for the polymorphic study of 15 C. globosum isolates. Twenty-two SSR markers showed average genetic polymorphism among C. globosum isolates. The number of alleles (Na) per marker ranges from 2 to 4, with a total of 74 alleles detected for 22 markers with a mean polymorphism information content (PIC) value of 0.4. UPGMA hierarchical clustering analysis generated three main clusters of C. globosum isolates and exhibited a lower similarity index range from 0.59 to 0.85. Thus, the newly developed EST-SSR markers could replace traditional methods for determining diversity. The study will also enhance the genomic research in C. globosum to explore its biocontrol potential against phytopathogens. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-023-03794-7.
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Affiliation(s)
- K. Darshan
- Division of Plant Pathology, Fungal Molecular Biology Laboratory, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
- Forest Protection Division, ICFRE-Tropical Forest Research Institute, Jabalpur, Madhya Pradesh 482021 India
| | - Rashmi Aggarwal
- Division of Plant Pathology, Fungal Molecular Biology Laboratory, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - Bishnu Maya Bashyal
- Division of Plant Pathology, Fungal Molecular Biology Laboratory, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - Jagmohan Singh
- Division of Plant Pathology, Fungal Molecular Biology Laboratory, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - M. S. Saharan
- Division of Plant Pathology, Fungal Molecular Biology Laboratory, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - M. S. Gurjar
- Division of Plant Pathology, Fungal Molecular Biology Laboratory, ICAR-Indian Agricultural Research Institute, New Delhi, 110012 India
| | - Amolkumar U. Solanke
- ICAR-National Institute for Plant Biotechnology, ICAR-IARI, New Delhi, 110012 India
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Bacher JW, Udho EB, Strauss EE, Vyazunova I, Gallinger S, Buchanan DD, Pai RK, Templeton AS, Storts DR, Eshleman JR, Halberg RB. A Highly Sensitive Pan-Cancer Test for Microsatellite Instability. J Mol Diagn 2023; 25:806-826. [PMID: 37544360 PMCID: PMC10629437 DOI: 10.1016/j.jmoldx.2023.07.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 07/10/2023] [Accepted: 07/18/2023] [Indexed: 08/08/2023] Open
Abstract
Microsatellite instability (MSI) is an evolving biomarker for cancer detection and treatment. MSI was first used to identify patients with Lynch syndrome, a hereditary form of colorectal cancer (CRC), but has recently become indispensable in predicting patient response to immunotherapy. To address the need for pan-cancer MSI detection, a new multiplex assay was developed that uses novel long mononucleotide repeat (LMR) markers to improve sensitivity. A total of 469 tumor samples from 20 different cancer types, including 319 from patients with Lynch syndrome, were tested for MSI using the new LMR MSI Analysis System. Results were validated by using deficient mismatch repair (dMMR) status according to immunohistochemistry as the reference standard and compared versus the Promega pentaplex MSI panel. The sensitivity of the LMR panel for detection of dMMR status by immunohistochemistry was 99% for CRC and 96% for non-CRC. The overall percent agreement between the LMR and Promega pentaplex panels was 99% for CRC and 89% for non-CRC tumors. An increased number of unstable markers and the larger size shifts observed in dMMR tumors using the LMR panel increased confidence in MSI determinations. The LMR MSI Analysis System expands the spectrum of cancer types in which MSI can be accurately detected.
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Affiliation(s)
- Jeffery W Bacher
- R&D Clinical Diagnostics, Promega Corporation, Madison, Wisconsin; Department of Medicine, University of Wisconsin, Madison, Wisconsin.
| | - Eshwar B Udho
- R&D Clinical Diagnostics, Promega Corporation, Madison, Wisconsin
| | | | - Irina Vyazunova
- R&D Clinical Diagnostics, Promega Corporation, Madison, Wisconsin
| | - Steven Gallinger
- Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Daniel D Buchanan
- Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia; Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Rish K Pai
- Health Science Research, Mayo Clinic, Scottsdale, Arizona
| | | | - Douglas R Storts
- R&D Clinical Diagnostics, Promega Corporation, Madison, Wisconsin
| | - James R Eshleman
- School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Richard B Halberg
- Department of Medicine, University of Wisconsin, Madison, Wisconsin; Department of Oncology, McArdle Laboratory of Cancer Research, University of Wisconsin, Madison, Wisconsin; University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
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18
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Zhuo J, Vasupalli N, Wang Y, Zhou G, Gao H, Zheng Y, Li B, Hou D, Lin X. Molecular identification of Bambusa changningensis is the natural bamboo hybrid of B. rigida × Dendrocalamus farinosus. FRONTIERS IN PLANT SCIENCE 2023; 14:1231940. [PMID: 37727859 PMCID: PMC10505617 DOI: 10.3389/fpls.2023.1231940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 08/09/2023] [Indexed: 09/21/2023]
Abstract
Bamboo is one of the fastest-growing plants commonly used in food, fibre, paper, biofuel, ornamental and medicinal industries. Natural hybridization in bamboo is rare due to its long vegetative period followed by gregarious flowering and death of the entire population. In the current study, a new bamboo species, Bambusa changningensis, shows intermediate characteristics of Dendrocalamus farinosus and B. rigida morphologically, but it is unknown whether B. changningensis is a natural hybrid. Moreover, B. changningensis has been identified as a superior variety of Sichuan Province with high pulping yield, fibre length and width. Therefore, we analyzed the morphological characteristics, DNA markers, DNA barcoding and chloroplast genomes to identify the hybrid origin of B. changningensis and possible maternal parent. We have developed the transcriptomic data for B. changningensis and mined the SSR loci. The putative parental lines and hybrid were screened for 64 SSR makers and identified that SSR14, SSR28, SSR31 and SSR34 markers showed both alleles of the parental species in B. changningensis, proving heterozygosity. Sequencing nuclear gene GBSSI partial regions and phylogenetic analysis also confirm the hybrid nature of B. changningensis. Further, we have generated the complete chloroplast genome sequence (139505 bp) of B. changningensis. By analyzing the cp genomes of both parents and B. changningensis, we identified that B. rigida might be the female parent. In conclusion, our study identified that B. changningensis is a natural hybrid, providing evidence for bamboo's natural hybridization. This is the first report on confirming a natural bamboo hybrid and its parents through SSR and chloroplast genome sequence.
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Affiliation(s)
- Juan Zhuo
- State Key Laboratory of Subtropical Silviculture, Zhejiang A & F University, Lin’An, Zhejiang, China
| | - Naresh Vasupalli
- State Key Laboratory of Subtropical Silviculture, Zhejiang A & F University, Lin’An, Zhejiang, China
| | - Yong Wang
- Forest and Bamboo Resources Conservation and Cultivation Institute, Yibin Forestry and Bamboo Industry Research Institute, Yibin, Sichuan, China
| | - Guoqiang Zhou
- Forest and Bamboo Resources Conservation and Cultivation Institute, Yibin Forestry and Bamboo Industry Research Institute, Yibin, Sichuan, China
| | - Huibin Gao
- Forest and Bamboo Resources Conservation and Cultivation Institute, Yibin Forestry and Bamboo Industry Research Institute, Yibin, Sichuan, China
| | - Ying Zheng
- State Key Laboratory of Subtropical Silviculture, Zhejiang A & F University, Lin’An, Zhejiang, China
| | - Benxiang Li
- Sichuan Changning Century Bamboo Garden, Yibin, Sichuan, China
| | - Dan Hou
- State Key Laboratory of Subtropical Silviculture, Zhejiang A & F University, Lin’An, Zhejiang, China
| | - Xinchun Lin
- State Key Laboratory of Subtropical Silviculture, Zhejiang A & F University, Lin’An, Zhejiang, China
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Duhan N, Kaur S, Kaundal R. ranchSATdb: A Genome-Wide Simple Sequence Repeat (SSR) Markers Database of Livestock Species for Mutant Germplasm Characterization and Improving Farm Animal Health. Genes (Basel) 2023; 14:1481. [PMID: 37510385 PMCID: PMC10378808 DOI: 10.3390/genes14071481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 07/13/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023] Open
Abstract
Microsatellites, also known as simple sequence repeats (SSRs), are polymorphic loci that play an important role in genome research, animal breeding, and disease control. Ranch animals are important components of agricultural landscape. The ranch animal SSR database, ranchSATdb, is a web resource which contains 15,520,263 putative SSR markers. This database provides a comprehensive tool for performing end-to-end marker selection, from SSRs prediction to generating marker primers and their cross-species feasibility, visualization of the resulting markers, and finding similarities between the genomic repeat sequences all in one place without the need to switch between other resources. The user-friendly online interface allows users to browse SSRs by genomic coordinates, repeat motif sequence, chromosome, motif type, motif frequency, and functional annotation. Users may enter their preferred flanking area around the repeat to retrieve the nucleotide sequence, they can investigate SSRs present in the genic or the genes between SSRs, they can generate custom primers, and they can also execute in silico validation of primers using electronic PCR. For customized sequences, an SSR prediction pipeline called miSATminer is also built. New species will be added to this website's database on a regular basis throughout time. To improve animal health via genomic selection, we hope that ranchSATdb will be a useful tool for mapping quantitative trait loci (QTLs) and marker-assisted selection. The web-resource is freely accessible at https://bioinfo.usu.edu/ranchSATdb/.
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Affiliation(s)
- Naveen Duhan
- Department of Plants, Soils, and Climate/Center for Integrated BioSystems, College of Agriculture and Applied Sciences, Utah State University, Logan, UT 84322, USA
- Bioinformatics Facility, Center for Integrated BioSystems, Utah State University, Logan, UT 84322, USA
| | - Simardeep Kaur
- Department of Plants, Soils, and Climate/Center for Integrated BioSystems, College of Agriculture and Applied Sciences, Utah State University, Logan, UT 84322, USA
- Division of Biochemistry, ICAR-Indian Agricultural Research Institute, New Delhi 110012, India
- ICAR-Research Complex for North Eastern Hill Region (NEH), Umiam 793103, India
| | - Rakesh Kaundal
- Department of Plants, Soils, and Climate/Center for Integrated BioSystems, College of Agriculture and Applied Sciences, Utah State University, Logan, UT 84322, USA
- Bioinformatics Facility, Center for Integrated BioSystems, Utah State University, Logan, UT 84322, USA
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20
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Shi W, Hu S, Song W, Huang Y, Shi C, Wang S. Uncovering the first complete chloroplast genomics, comparative analysis, and phylogenetic relationships of the medicinal plants Rhamnus cathartica and Frangula alnus ( Rhamnaceae). PHYSIOLOGY AND MOLECULAR BIOLOGY OF PLANTS : AN INTERNATIONAL JOURNAL OF FUNCTIONAL PLANT BIOLOGY 2023; 29:855-869. [PMID: 37520808 PMCID: PMC10382440 DOI: 10.1007/s12298-023-01331-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 06/04/2023] [Accepted: 07/05/2023] [Indexed: 08/01/2023]
Abstract
Rhamnus cathartica and Frangula alnus are economically valuable medicinal plants from the Rhamnaceae family. However, their chloroplast genome structure, phylogenetic position, relationships, and evolution remain poorly understood. Herein, the complete chloroplast genome resources of R. cathartica and F. alnus have been added. The first comparative analysis of the Rhamnus and Frangula species based on complete chloroplast genomes was provided. The chloroplast genomes of R. cathartica and F. alnus exhibited a quadripartite structure, with total lengths of 161,149 bp and 161,255 bp, respectively. The lack of the infA and psbL genes does not negatively impact the normal functioning of Rhamnus and Frangula species. The rpl20 and rpl33 genes are undergoing rapid evolution. Rhamnus and Frangula species prefer amino acids with A/U-terminal codons. There were between 100 and 126 simple sequence repeats and between 38 and 100 long repeats. Several highly divergent intergenic regions (trnK-UUU-trnQ-UUG, atpH-atpI, trnY-GUA-trnE-UUC, trnG-GCC-trnfM-CAU, trnT-UGU-trnF-GAA, rpl20-rps12, and rpl22-rps19) and highly divergent genes (ycf3, ndhA, rpl32, and ycf1) were identified, which could serve as potential phylogenetic markers due to their variability. We reconstructed the phylogenetic relationships among Rhamnus species and F. alnus using complete chloroplast genomes. There is no significant correlation between the medicinal value of the species analyzed and their phylogenetic relationships. These results provide valuable insights for understanding the phylogenetic relationship and evolution of Rhamnus and Frangula species. These findings could serve as a foundation for future studies on the Rhamnaceae. Supplementary Information The online version contains supplementary material available at 10.1007/s12298-023-01331-7.
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Affiliation(s)
- Wenbo Shi
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao, 266042 China
| | - Siqi Hu
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao, 266042 China
| | - Weicai Song
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao, 266042 China
| | - Yahui Huang
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao, 266042 China
| | - Chao Shi
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao, 266042 China
- Plant Germplasm and Genomics Center, Germplasm Bank of Wild Species in Southwest China, Kunming Institute of Botany, The Chinese Academy of Sciences, Kunming, 650204 China
| | - Shuo Wang
- College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao, 266042 China
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21
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Shi Y, Niu Y, Zhang P, Luo H, Liu S, Zhang S, Wang J, Li Y, Liu X, Song T, Xu T, He S. Characterization of genome-wide STR variation in 6487 human genomes. Nat Commun 2023; 14:2092. [PMID: 37045857 PMCID: PMC10097659 DOI: 10.1038/s41467-023-37690-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 03/27/2023] [Indexed: 04/14/2023] Open
Abstract
Short tandem repeats (STRs) are abundant and highly mutagenic in the human genome. Many STR loci have been associated with a range of human genetic disorders. However, most population-scale studies on STR variation in humans have focused on European ancestry cohorts or are limited by sequencing depth. Here, we depicted a comprehensive map of 366,013 polymorphic STRs (pSTRs) constructed from 6487 deeply sequenced genomes, comprising 3983 Chinese samples (~31.5x, NyuWa) and 2504 samples from the 1000 Genomes Project (~33.3x, 1KGP). We found that STR mutations were affected by motif length, chromosome context and epigenetic features. We identified 3273 and 1117 pSTRs whose repeat numbers were associated with gene expression and 3'UTR alternative polyadenylation, respectively. We also implemented population analysis, investigated population differentiated signatures, and genotyped 60 known disease-causing STRs. Overall, this study further extends the scale of STR variation in humans and propels our understanding of the semantics of STRs.
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Affiliation(s)
- Yirong Shi
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yiwei Niu
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Peng Zhang
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Huaxia Luo
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Shuai Liu
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Sijia Zhang
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Jiajia Wang
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Yanyan Li
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Xinyue Liu
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Tingrui Song
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Tao Xu
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
- Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
| | - Shunmin He
- Key Laboratory of RNA Biology, Center for Big Data Research in Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
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22
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Kurokawa R, Kurokawa M, Mitsutake A, Nakaya M, Baba A, Nakata Y, Moritani T, Abe O. Clinical and neuroimaging review of triplet repeat diseases. Jpn J Radiol 2023; 41:115-130. [PMID: 36169768 PMCID: PMC9889482 DOI: 10.1007/s11604-022-01343-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 09/18/2022] [Indexed: 02/04/2023]
Abstract
Triplet repeat diseases (TRDs) refer to a group of diseases caused by three nucleotide repeats elongated beyond a pathologic threshold. TRDs are divided into the following four groups depending on the pathomechanisms, although the pathomechanisms of several diseases remain unelucidated: polyglutamine disorders, caused by a pathologic repeat expansion of CAG (coding the amino acid glutamine) located within the exon; loss-of-function repeat disorders, characterized by the common feature of a loss of function of the gene within which they occur; RNA gain-of-function disorders, involving the production of a toxic RNA species; and polyalanine disorders, caused by a pathologic repeat expansion of GCN (coding the amino acid alanine) located within the exon. Many of these TRDs manifest through neurologic symptoms; moreover, neuroimaging, especially brain magnetic resonance imaging, plays a pivotal role in the detection of abnormalities, differentiation, and management of TRDs. In this article, we reviewed the clinical and neuroimaging features of TRDs. An early diagnosis of TRDs through clinical and imaging approaches is important and may contribute to appropriate medical intervention for patients and their families.
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Affiliation(s)
- Ryo Kurokawa
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan ,Division of Neuroradiology, Department of Radiology, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109 USA
| | - Mariko Kurokawa
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan ,Division of Neuroradiology, Department of Radiology, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109 USA
| | - Akihiko Mitsutake
- Department of Neurology, International University of Health and Welfare, Mita Hospital, 1-4-3 Mita, Minato-ku, Tokyo, 108-8329 Japan
| | - Moto Nakaya
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan
| | - Akira Baba
- Division of Neuroradiology, Department of Radiology, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109 USA
| | - Yasuhiro Nakata
- Department of Neuroradiology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu, Tokyo 183-0042 Japan
| | - Toshio Moritani
- Division of Neuroradiology, Department of Radiology, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109 USA
| | - Osamu Abe
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan
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23
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Liu Y, Wan L, Ngai CK, Wang Y, Lam SL, Guo P. Structures and conformational dynamics of DNA minidumbbells in pyrimidine-rich repeats associated with neurodegenerative diseases. Comput Struct Biotechnol J 2023; 21:1584-1592. [PMID: 36874156 PMCID: PMC9975016 DOI: 10.1016/j.csbj.2023.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 02/05/2023] [Accepted: 02/05/2023] [Indexed: 02/10/2023] Open
Abstract
Expansions of short tandem repeats (STRs) are associated with approximately 50 human neurodegenerative diseases. These pathogenic STRs are prone to form non-B DNA structure, which has been considered as one of the causative factors for repeat expansions. Minidumbbell (MDB) is a relatively new type of non-B DNA structure formed by pyrimidine-rich STRs. An MDB is composed of two tetraloops or pentaloops, exhibiting a highly compact conformation with extensive loop-loop interactions. The MDB structures have been found to form in CCTG tetranucleotide repeats associated with myotonic dystrophy type 2, ATTCT pentanucleotide repeats associated with spinocerebellar ataxia type 10, and the recently discovered ATTTT/ATTTC repeats associated with spinocerebellar ataxia type 37 and familial adult myoclonic epilepsy. In this review, we first introduce the structures and conformational dynamics of MDBs with a focus on the high-resolution structural information determined by nuclear magnetic resonance spectroscopy. Then we discuss the effects of sequence context, chemical environment, and nucleobase modification on the structure and thermostability of MDBs. Finally, we provide perspectives on further explorations of sequence criteria and biological functions of MDBs.
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Affiliation(s)
- Yuan Liu
- South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou, Guangdong 510640, China
| | - Liqi Wan
- School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Cheuk Kit Ngai
- Department of Chemistry, The Chinese University of Hong Kong, Shatin N.T., Hong Kong, China
| | - Yang Wang
- Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
| | - Sik Lok Lam
- Department of Chemistry, The Chinese University of Hong Kong, Shatin N.T., Hong Kong, China
| | - Pei Guo
- Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
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24
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Steely CJ, Watkins WS, Baird L, Jorde LB. The mutational dynamics of short tandem repeats in large, multigenerational families. Genome Biol 2022; 23:253. [PMID: 36510265 PMCID: PMC9743774 DOI: 10.1186/s13059-022-02818-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 11/17/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Short tandem repeats (STRs) compose approximately 3% of the genome, and mutations at STR loci have been linked to dozens of human diseases including amyotrophic lateral sclerosis, Friedreich ataxia, Huntington disease, and fragile X syndrome. Improving our understanding of these mutations would increase our knowledge of the mutational dynamics of the genome and may uncover additional loci that contribute to disease. To estimate the genome-wide pattern of mutations at STR loci, we analyze blood-derived whole-genome sequencing data for 544 individuals from 29 three-generation CEPH pedigrees. These pedigrees contain both sets of grandparents, the parents, and an average of 9 grandchildren per family. RESULTS We use HipSTR to identify de novo STR mutations in the 2nd generation of these pedigrees and require transmission to the third generation for validation. Analyzing approximately 1.6 million STR loci, we estimate the empirical de novo STR mutation rate to be 5.24 × 10-5 mutations per locus per generation. Perfect repeats mutate about 2 × more often than imperfect repeats. De novo STRs are significantly enriched in Alu elements. CONCLUSIONS Approximately 30% of new STR mutations occur within Alu elements, which compose only 11% of the genome, but only 10% are found in LINE-1 insertions, which compose 17% of the genome. Phasing these mutations to the parent of origin shows that parental transmission biases vary among families. We estimate the average number of de novo genome-wide STR mutations per individual to be approximately 85, which is similar to the average number of observed de novo single nucleotide variants.
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Affiliation(s)
- Cody J. Steely
- grid.223827.e0000 0001 2193 0096Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112 USA
| | - W. Scott Watkins
- grid.223827.e0000 0001 2193 0096Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112 USA
| | - Lisa Baird
- grid.223827.e0000 0001 2193 0096Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112 USA
| | - Lynn B. Jorde
- grid.223827.e0000 0001 2193 0096Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112 USA
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25
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Morales-Juarez DA, Jackson SP. Clinical prospects of WRN inhibition as a treatment for MSI tumours. NPJ Precis Oncol 2022; 6:85. [PMID: 36379964 PMCID: PMC9666358 DOI: 10.1038/s41698-022-00319-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 10/06/2022] [Indexed: 11/17/2022] Open
Abstract
The discovery of synthetic lethal interactions with genetic deficiencies in cancers has highlighted several candidate targets for drug development, with variable clinical success. Recent work has unveiled a promising synthetic lethal interaction between inactivation/inhibition of the WRN DNA helicase and tumours with microsatellite instability, a phenotype that arises from DNA mismatch repair deficiency. While these and further studies have highlighted the therapeutic potential of WRN inhibitors, compounds with properties suitable for clinical exploitation remain to be described. Furthermore, the complexities of MSI development and its relationship to cancer evolution pose challenges for clinical prospects. Here, we discuss possible paths of MSI tumour development, the viability of WRN inhibition as a strategy in different scenarios, and the necessary conditions to create a roadmap towards successful implementation of WRN inhibitors in the clinic.
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Affiliation(s)
- David A Morales-Juarez
- Wellcome and Cancer Research UK Gurdon Institute, and Department of Biochemistry, University of Cambridge, Cambridge, UK.
| | - Stephen P Jackson
- Wellcome and Cancer Research UK Gurdon Institute, and Department of Biochemistry, University of Cambridge, Cambridge, UK.
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
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26
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Wang L, Zhang S, Fang J, Jin X, Mamut R, Li P. The Chloroplast Genome of the Lichen Photobiont Trebouxiophyceae sp. DW1 and Its Phylogenetic Implications. Genes (Basel) 2022; 13:genes13101840. [PMID: 36292725 PMCID: PMC9601494 DOI: 10.3390/genes13101840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/30/2022] [Accepted: 10/10/2022] [Indexed: 11/16/2022] Open
Abstract
Lichens are symbiotic associations of algae and fungi. The genetic mechanism of the symbiosis of lichens and the influence of symbiosis on the size and composition of the genomes of symbiotic algae have always been intriguing scientific questions explored by lichenologists. However, there were limited data on lichen genomes. Therefore, we isolated and purified a lichen symbiotic alga to obtain a single strain (Trebouxiophyceae sp. DW1), and then obtained its chloroplast genome information by next-generation sequencing (NGS). The chloroplast genome is 129,447 bp in length, and the GC content is 35.2%. Repetitive sequences with the length of 30–35 bp account for 1.27% of the total chloroplast genome. The simple sequence repeats are all mononucleotide repeats. Codon usage analysis showed that the genome tended to use codon ending in A/U. By comparing the length of different regions of Trebouxiophyceae genomes, we found that the changes in the length of exons, introns, and intergenic sequences affect the size of genomes. Trebouxiophyceae had an unstable chloroplast genome structure, with IRs repeatedly losing during evolution. Phylogenetic analysis showed that Trebouxiophyceae is paraphyletic, and Trebouxiophyceae sp. DW1 is sister to the clade of Koliella longiseta and Pabia signiensis.
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Affiliation(s)
- Lidan Wang
- College of Life Sciences and Technology, Xinjiang University, Urumchi 830046, China
| | - Shenglu Zhang
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jinjin Fang
- College of Life Sciences and Technology, Xinjiang University, Urumchi 830046, China
| | - Xinjie Jin
- College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China
| | - Reyim Mamut
- College of Life Sciences and Technology, Xinjiang University, Urumchi 830046, China
- Correspondence: (R.M.); (P.L.)
| | - Pan Li
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China
- Correspondence: (R.M.); (P.L.)
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27
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Keerti A, Ninave S. DNA Fingerprinting: Use of Autosomal Short Tandem Repeats in Forensic DNA Typing. Cureus 2022; 14:e30210. [DOI: 10.7759/cureus.30210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 10/11/2022] [Indexed: 11/06/2022] Open
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28
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Masnovo C, Lobo AF, Mirkin SM. Replication dependent and independent mechanisms of GAA repeat instability. DNA Repair (Amst) 2022; 118:103385. [PMID: 35952488 PMCID: PMC9675320 DOI: 10.1016/j.dnarep.2022.103385] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 07/28/2022] [Accepted: 07/30/2022] [Indexed: 11/20/2022]
Abstract
Trinucleotide repeat instability is a driver of human disease. Large expansions of (GAA)n repeats in the first intron of the FXN gene are the cause Friedreich's ataxia (FRDA), a progressive degenerative disorder which cannot yet be prevented or treated. (GAA)n repeat instability arises during both replication-dependent processes, such as cell division and intergenerational transmission, as well as in terminally differentiated somatic tissues. Here, we provide a brief historical overview on the discovery of (GAA)n repeat expansions and their association to FRDA, followed by recent advances in the identification of triplex H-DNA formation and replication fork stalling. The main body of this review focuses on the last decade of progress in understanding the mechanism of (GAA)n repeat instability during DNA replication and/or DNA repair. We propose that the discovery of additional mechanisms of (GAA)n repeat instability can be achieved via both comparative approaches to other repeat expansion diseases and genome-wide association studies. Finally, we discuss the advances towards FRDA prevention or amelioration that specifically target (GAA)n repeat expansions.
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Affiliation(s)
- Chiara Masnovo
- Department of Biology, Tufts University, Medford, MA 02155, USA
| | - Ayesha F Lobo
- Department of Biology, Tufts University, Medford, MA 02155, USA
| | - Sergei M Mirkin
- Department of Biology, Tufts University, Medford, MA 02155, USA.
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29
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Microsatellite Variation in the Most Devastating Beetle Pests (Coleoptera: Curculionidae) of Agricultural and Forest Crops. Int J Mol Sci 2022; 23:ijms23179847. [PMID: 36077247 PMCID: PMC9456221 DOI: 10.3390/ijms23179847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 08/19/2022] [Accepted: 08/24/2022] [Indexed: 12/03/2022] Open
Abstract
Weevils, classified in the family Curculionidae (true weevils), constitute a group of phytophagous insects of which many species are considered significant pests of crops. Within this family, the red palm weevil (RPW), Rhynchophorus ferrugineus, has an integral role in destroying crops and has invaded all countries of the Middle East and many in North Africa, Southern Europe, Southeast Asia, Oceania, and the Caribbean Islands. Simple sequence repeats (SSRs), also termed microsatellites, have become the DNA marker technology most applied to study population structure, evolution, and genetic diversity. Although these markers have been widely examined in many mammalian and plant species, and draft genome assemblies are available for many species of true weevils, very little is yet known about SSRs in weevil genomes. Here we carried out a comparative analysis examining and comparing the relative abundance, relative density, and GC content of SSRs in previously sequenced draft genomes of nine true weevils, with an emphasis on R. ferrugineus. We also used Illumina paired-end sequencing to generate draft sequence for adult female RPW and characterized it in terms of perfect SSRs with 1–6 bp nucleotide motifs. Among weevil genomes, mono- to trinucleotide SSRs were the most frequent, and mono-, di-, and hexanucleotide SSRs exhibited the highest GC content. In these draft genomes, SSR number and genome size were significantly correlated. This work will aid our understanding of the genome architecture and evolution of Curculionidae weevils and facilitate exploring SSR molecular marker development in these species.
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30
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Wang Y, Sha H, Li X, Zhou T, Luo X, Zou G, Chai Y, Liang H. Microsatellite Characteristics of Silver Carp ( Hypophthalmichthysmolitrix) Genome and Genetic Diversity Analysis in Four Cultured Populations. Genes (Basel) 2022; 13:genes13071267. [PMID: 35886050 PMCID: PMC9320178 DOI: 10.3390/genes13071267] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/07/2022] [Accepted: 07/12/2022] [Indexed: 02/04/2023] Open
Abstract
Hypophthalmichthys molitrix is one of the four most important fish in China and has high breeding potential. However, simple sequence repeat (SSR) markers developed on H. molitrix genome level for genetic diversity analysis are limited. In this study, the distribution characteristics of SSRs in the assembled H. molitrix genome were analyzed, and new markers were developed to preliminarily evaluate the genetic diversity of the four breeding populations. A total of 368,572 SSRs were identified from the H. molitrix genome. The total length of SSRs was 6,492,076 bp, accounting for 0.77% of the total length of the genome sequence. The total frequency and total density were 437.73 loci/Mb and 7713.16 bp/Mb, respectively. Among the 2–6 different nucleotide repeat types, SSRs were dominated by di-nucleotide repeats (204,873, 55.59%), and AC/GT was the most abundant motif. The number of SSRs on each chromosome was positively correlated with the length. The 13 pairs of markers developed were used to analyze the genetic diversity of four cultivated populations in Hubei Province. The results showed that the genetic diversity of the four populations was low, and the ranges of alleles (Na), effective alleles (Ne), observed heterozygosity (Ho), and Shannon’s index information (I) were 3.538–4.462, 2.045–2.461, 0.392–0.450, and 0.879–0.954, respectively. Genetic variation occurs mainly among individuals within populations (95.35%). UPGMA tree and Bayesian analysis showed that four populations could be divided into two different branches. Therefore, the genome-wide SSRs were effectively in genetic diversity analysis on H. molitrix.
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Affiliation(s)
- Yajun Wang
- Engineering Research Center of Ecology and Agricultural Use of Wetland, Ministry of Education, College of Agriculture, College of Animal Science, Yangtze University, Jingzhou 434025, China;
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China; (H.S.); (X.L.); (T.Z.); (X.L.); (G.Z.)
| | - Hang Sha
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China; (H.S.); (X.L.); (T.Z.); (X.L.); (G.Z.)
| | - Xiaohui Li
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China; (H.S.); (X.L.); (T.Z.); (X.L.); (G.Z.)
| | - Tong Zhou
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China; (H.S.); (X.L.); (T.Z.); (X.L.); (G.Z.)
| | - Xiangzhong Luo
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China; (H.S.); (X.L.); (T.Z.); (X.L.); (G.Z.)
| | - Guiwei Zou
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China; (H.S.); (X.L.); (T.Z.); (X.L.); (G.Z.)
| | - Yi Chai
- Engineering Research Center of Ecology and Agricultural Use of Wetland, Ministry of Education, College of Agriculture, College of Animal Science, Yangtze University, Jingzhou 434025, China;
- Correspondence: (Y.C.); (H.L.)
| | - Hongwei Liang
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China; (H.S.); (X.L.); (T.Z.); (X.L.); (G.Z.)
- Correspondence: (Y.C.); (H.L.)
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31
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Halman A, Dolzhenko E, Oshlack A. STRipy: A graphical application for enhanced genotyping of pathogenic short tandem repeats in sequencing data. Hum Mutat 2022; 43:859-868. [PMID: 35395114 PMCID: PMC9541159 DOI: 10.1002/humu.24382] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 12/01/2021] [Accepted: 04/06/2022] [Indexed: 11/22/2022]
Abstract
Expansions of short tandem repeats (STRs) have been implicated as the causal variant in over 50 diseases known to date. There are several tools which can genotype STRs from high-throughput sequencing (HTS) data. However, running these tools out of the box only allows around half of the known disease-causing loci to be genotyped. Furthermore, the genotypes estimated at these loci are often underestimated with maximum lengths limited to either the read or fragment length, which is less than the pathogenic cutoff for some diseases. Although analysis tools can be customized to genotype extra loci, this requires proficiency in bioinformatics to set up, limiting their widespread usage by other researchers and clinicians. To address these issues, we have developed a new software called STRipy, which is able to target all known disease-causing STRs from HTS data. We created an intuitive graphical interface for STRipy and significantly simplified the detection of STRs expansions. Moreover, we genotyped all disease loci for over two and half thousand samples to provide population-wide distributions to assist with interpretation of results. We believe the simplicity and breadth of STRipy will increase the genotyping of STRs in sequencing data resulting in further diagnoses of rare STR diseases.
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Affiliation(s)
- Andreas Halman
- Peter MacCallum Cancer CentreMelbourneVictoriaAustralia
- Sir Peter MacCallum Department of OncologyThe University of MelbourneParkvilleVictoriaAustralia
- Murdoch Children's Research Institute, Royal Children's HospitalParkvilleVictoriaAustralia
- Florey Department of Neuroscience and Mental HealthThe University of MelbourneParkvilleVictoriaAustralia
- School of Natural Sciences and HealthTallinn UniversityTallinnEstonia
| | | | - Alicia Oshlack
- Peter MacCallum Cancer CentreMelbourneVictoriaAustralia
- Sir Peter MacCallum Department of OncologyThe University of MelbourneParkvilleVictoriaAustralia
- School of BioSciencesUniversity of MelbourneParkvilleVictoriaAustralia
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32
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Liufu T, Zheng Y, Yu J, Yuan Y, Wang Z, Deng J, Hong D. The polyG diseases: a new disease entity. Acta Neuropathol Commun 2022; 10:79. [PMID: 35642014 PMCID: PMC9153130 DOI: 10.1186/s40478-022-01383-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 05/16/2022] [Indexed: 12/20/2022] Open
Abstract
Recently, inspired by the similar clinical and pathological features shared with fragile X-associated tremor/ataxia syndrome (FXTAS), abnormal expansion of CGG repeats in the 5' untranslated region has been found in neuronal intranuclear inclusion disease (NIID), oculopharyngeal myopathy with leukoencephalopathy (OPML), and oculopharyngodistal myopathy (OPDMs). Although the upstream open reading frame has not been elucidated in OPML and OPDMs, polyglycine (polyG) translated by expanded CGG repeats is reported to be as a primary pathogenesis in FXTAS and NIID. Collectively, these findings indicate a new disease entity, the polyG diseases. In this review, we state the common clinical manifestations, pathological features, mechanisms, and potential therapies in these diseases, and provide preliminary opinions about future research in polyG diseases.
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Affiliation(s)
- Tongling Liufu
- Department of Neurology, Peking University First Hospital, Beijing, China
| | - Yilei Zheng
- Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jiaxi Yu
- Department of Neurology, Peking University First Hospital, Beijing, China
| | - Yun Yuan
- Department of Neurology, Peking University First Hospital, Beijing, China
| | - Zhaoxia Wang
- Department of Neurology, Peking University First Hospital, Beijing, China.,Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, China
| | - Jianwen Deng
- Department of Neurology, Peking University First Hospital, Beijing, China. .,Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, China.
| | - Daojun Hong
- Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, China. .,Department of Medical Genetics, The First Affiliated Hospital of Nanchang University, Nanchang, China.
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33
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Tang J, Yao D, Zhou H, Du L, Daroch M. Reevaluation of Parasynechococcus-like Strains and Genomic Analysis of Their Microsatellites and Compound Microsatellites. PLANTS (BASEL, SWITZERLAND) 2022; 11:plants11081060. [PMID: 35448788 PMCID: PMC9024877 DOI: 10.3390/plants11081060] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 04/06/2022] [Accepted: 04/11/2022] [Indexed: 05/28/2023]
Abstract
Morphologically similar to Synechococcus, a large number of Parasynechococcus strains were misclassified, resulting in extreme underestimation of their genetic diversity. In this study, 80 Synechococcus-like strains were reevaluated using a combination of 16S rRNA phylogeny and genomic approach, identifying 54 strains as Parasynechococcus-like strains and showing considerably intragenus genetic divergence among the subclades identified. Further, bioinformatics analysis disclosed diversified patterns of distribution, abundance, density, and diversity of microsatellites (SSRs) and compound microsatellites (CSSRs) in genomes of these Parasynechococcus-like strains. Variations of SSRs and CSSRs were observed amongst phylotypes and subclades. Both SSRs and CSSRs were in particular unequally distributed among genomes. Dinucleotide SSRs were the most widespread, while the genomes showed two patterns in the second most abundant repeat type (mononucleotide or trinucleotide SSRs). Both SSRs and CSSRs were predominantly observed in coding regions. These two types of microsatellites showed positive correlation with genome size (p < 0.01) but negative correlation with GC content (p < 0.05). Additionally, the motif (A)n, (AG)n and (AGC)n was a major one in the corresponding category. Meanwhile, distinctive motifs of CSSRs were found in 39 genomes. This study characterizes SSRs and CSSRs in genomes of Parasynechococcus-like strains and will be useful as a prerequisite for future studies regarding their distribution, function, and evolution. Moreover, the identified SSRs may facilitate fast acclimation of Parasynechococcus-like strains to fluctuating environments and contribute to the extensive distribution of Parasynechococcus species in global marine environments.
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Affiliation(s)
- Jie Tang
- School of Food and Bioengineering, Chengdu University, Chengdu 610106, China; (J.T.); (D.Y.); (H.Z.); (L.D.)
| | - Dan Yao
- School of Food and Bioengineering, Chengdu University, Chengdu 610106, China; (J.T.); (D.Y.); (H.Z.); (L.D.)
| | - Huizhen Zhou
- School of Food and Bioengineering, Chengdu University, Chengdu 610106, China; (J.T.); (D.Y.); (H.Z.); (L.D.)
| | - Lianming Du
- School of Food and Bioengineering, Chengdu University, Chengdu 610106, China; (J.T.); (D.Y.); (H.Z.); (L.D.)
| | - Maurycy Daroch
- School of Environment and Energy, Peking University Shenzhen Graduate School, 2199 Lishui Road, Shenzhen 518055, China
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34
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Tak YE, Boulay G, Lee L, Iyer S, Perry NT, Schultz HT, Garcia SP, Broye L, Horng JE, Rengarajan S, Naigles B, Volorio A, Sander JD, Gong J, Riggi N, Joung JK, Rivera MN. Genome-wide functional perturbation of human microsatellite repeats using engineered zinc finger transcription factors. CELL GENOMICS 2022; 2. [PMID: 35967079 PMCID: PMC9374162 DOI: 10.1016/j.xgen.2022.100119] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Y. Esther Tak
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA
- Department of Pathology, Harvard Medical School, Boston, MA, USA
| | - Gaylor Boulay
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
- Department of Pathology, Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Lukuo Lee
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
| | - Sowmya Iyer
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
| | - Nicholas T. Perry
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA
| | - Hayley T. Schultz
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA
| | - Sara P. Garcia
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
| | - Liliane Broye
- Institute of Pathology, Department of Experimental Pathology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland
| | - Joy E. Horng
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA
| | - Shruthi Rengarajan
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
| | - Beverly Naigles
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
| | - Angela Volorio
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
- Institute of Pathology, Department of Experimental Pathology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland
| | - Jeffry D. Sander
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA
- Department of Pathology, Harvard Medical School, Boston, MA, USA
| | - Jingyi Gong
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA
| | - Nicolò Riggi
- Institute of Pathology, Department of Experimental Pathology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland
- Corresponding author
| | - J. Keith Joung
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA, USA
- Department of Pathology, Harvard Medical School, Boston, MA, USA
- Corresponding author
| | - Miguel N. Rivera
- Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA
- Department of Pathology, Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Corresponding author
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35
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Genome-Wide Survey and Development of the First Microsatellite Markers Database ( AnCorDB) in Anemone coronaria L. Int J Mol Sci 2022; 23:ijms23063126. [PMID: 35328546 PMCID: PMC8949970 DOI: 10.3390/ijms23063126] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 03/08/2022] [Accepted: 03/10/2022] [Indexed: 12/31/2022] Open
Abstract
Anemone coronaria L. (2n = 2x = 16) is a perennial, allogamous, highly heterozygous plant marketed as a cut flower or in gardens. Due to its large genome size, limited efforts have been made in order to develop species-specific molecular markers. We obtained the first draft genome of the species by Illumina sequencing an androgenetic haploid plant of the commercial line “MISTRAL® Magenta”. The genome assembly was obtained by applying the MEGAHIT pipeline and consisted of 2 × 106 scaffolds. The SciRoKo SSR (Simple Sequence Repeats)-search module identified 401.822 perfect and 188.987 imperfect microsatellites motifs. Following, we developed a user-friendly “Anemone coronaria Microsatellite DataBase” (AnCorDB), which incorporates the Primer3 script, making it possible to design couples of primers for downstream application of the identified SSR markers. Eight genotypes belonging to eight cultivars were used to validate 62 SSRs and a subset of markers was applied for fingerprinting each cultivar, as well as to assess their intra-cultivar variability. The newly developed microsatellite markers will find application in Breeding Rights disputes, developing genetic maps, marker assisted breeding (MAS) strategies, as well as phylogenetic studies.
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36
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Genome-wide SSR markers in bottle gourd: development, characterization, utilization in assessment of genetic diversity of National Genebank of India and synteny with other related cucurbits. J Appl Genet 2022; 63:237-263. [PMID: 35106708 DOI: 10.1007/s13353-022-00684-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/06/2022] [Accepted: 01/15/2022] [Indexed: 10/19/2022]
Abstract
Lagenaria siceraria (Molina) Standley is an important cultivated crop with its immense importance in pharmaceutical industry and as vegetable. Its seed, root, stem, leaves, flower, and fruit are used as an ointment for ailment of various diseases throughout Asia. Despite its worldwide importance, informative co-dominant microsatellite markers in the bottle gourd crop are very restricted, impeding genetic improvement, cultivar identification, and phylogenetic studies. Next-generation sequencing has revolutionized the approaches for discovery, assessment, and validation of molecular markers. We conducted a genome-wide analysis, for developing SSR markers by utilizing restriction site-associated DNA sequencing (RAD-Seq) data obtained from NCBI. By performing in silico mining of microsatellite repeat motifs, we developed 45,066 perfect SSR markers. Of which 207 markers were successfully validated and 120 (57.97%) polymorphic primer pairs were utilized for an in-depth genetic diversity and population structure analysis of 96 accessions from the National Genebank of India. Tetranucleotide repeats (∼34.3%) were the most prevalent followed by trinucleotide repeats (∼30.73%), further 21.03%, 9.6%, and 4.3% of di-, penta-, and hexa-nucleotide repeats in the bottle gourd genome, respectively. Synteny of SSR markers on 11 bottle gourd linkage groups was correlated with the 7 chromosomes of cucumber (93.2%), 12 chromosomes of melon (87.4%), and 11 of watermelon (90.8%). The generated SSR markers provide a valuable tool for germplasm characterization, genetic linkage map construction, studying synteny, gene discovery, and for breeding in bottle gourd and other cucurbits species. KEY MESSAGE: Development of 45,066 perfect microsatellite markers as a valuable tool for marker assisted selection (MAS) in plant breeding.
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37
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Annear DJ, Vandeweyer G, Sanchis-Juan A, Raymond FL, Kooy RF. Non-Mendelian inheritance patterns and extreme deviation rates of CGG repeats in autism. Genome Res 2022; 32:1967-1980. [PMID: 36351771 PMCID: PMC9808627 DOI: 10.1101/gr.277011.122] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 10/14/2022] [Indexed: 11/10/2022]
Abstract
As expansions of CGG short tandem repeats (STRs) are established as the genetic etiology of many neurodevelopmental disorders, we aimed to elucidate the inheritance patterns and role of CGG STRs in autism-spectrum disorder (ASD). By genotyping 6063 CGG STR loci in a large cohort of trios and quads with an ASD-affected proband, we determined an unprecedented rate of CGG repeat length deviation across a single generation. Although the concept of repeat length being linked to deviation rate was solidified, we show how shorter STRs display greater degrees of size variation. We observed that CGG STRs did not segregate by Mendelian principles but with a bias against longer repeats, which appeared to magnify as repeat length increased. Through logistic regression, we identified 19 genes that displayed significantly higher rates and degrees of CGG STR expansion within the ASD-affected probands (P < 1 × 10-5). This study not only highlights novel repeat expansions that may play a role in ASD but also reinforces the hypothesis that CGG STRs are specifically linked to human cognition.
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Affiliation(s)
- Dale J. Annear
- Department of Medical Genetics, University of Antwerp, 2600 Antwerp, Belgium
| | - Geert Vandeweyer
- Department of Medical Genetics, University of Antwerp, 2600 Antwerp, Belgium
| | - Alba Sanchis-Juan
- NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, United Kingdom;,Department of Haematology, University of Cambridge, NHS Blood and Transplant Centre, Cambridge, CB2 0PT, United Kingdom
| | - F. Lucy Raymond
- NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, United Kingdom;,Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, United Kingdom
| | - R. Frank Kooy
- Department of Medical Genetics, University of Antwerp, 2600 Antwerp, Belgium
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38
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Yao D, Cheng L, Du L, Li M, Daroch M, Tang J. Genome-Wide Investigation and Analysis of Microsatellites and Compound Microsatellites in Leptolyngbya-like Species, Cyanobacteria. Life (Basel) 2021; 11:life11111258. [PMID: 34833134 PMCID: PMC8619395 DOI: 10.3390/life11111258] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/03/2021] [Accepted: 11/16/2021] [Indexed: 01/12/2023] Open
Abstract
Microsatellites (simple sequence repeats, SSRs) are ubiquitously distributed in almost all known genomes. Here, the first investigation was designed to examine the SSRs and compound microsatellites (CSSRs) in genomes of Leptolyngbya-like strains. The results disclosed diversified patterns of distribution, abundance, density, and diversity of SSRs and CSSRs in genomes, indicating that they may be subject to rapid evolutionary change. The numbers of SSRs and CSSRs were extremely unevenly distributed among genomes, ranging from 11,086 to 24,000 and from 580 to 1865, respectively. Dinucleotide SSRs were the most abundant category in 31 genomes, while the other 15 genomes followed the pattern: mono- > di- > trinucleotide SSRs. The patterns related to SSRs and CSSRs showed differences among phylogenetic groups. Both SSRs and CSSRs were overwhelmingly distributed in coding regions. The numbers of SSRs and CSSRs were significantly positively correlated with genome size (p < 0.01) and negatively correlated with GC content (p < 0.05). Moreover, the motif (A/C)n and (AG)n was predominant in mononucleotide and dinucleotide SSRs, and unique motifs of CSSRs were identified in 39 genomes. This study provides the first insight into SSRs and CSSRs in genomes of Leptolyngbya-like strains and will be useful to understanding their distribution, predicting their function, and tracking their evolution. Additionally, the identified SSRs may provide an evolutionary advantage of fast adaptation to environmental changes and may play an important role in the cosmopolitan distribution of Leptolyngbya strains to globally diverse niches.
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Affiliation(s)
- Dan Yao
- Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu 610106, China; (D.Y.); (L.D.)
| | - Lei Cheng
- Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology & Business University, Beijing 100048, China;
| | - Lianming Du
- Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu 610106, China; (D.Y.); (L.D.)
| | - Meijin Li
- School of Environment and Energy, Peking University Shenzhen Graduate School, Shenzhen 518055, China; (M.L.); (M.D.)
| | - Maurycy Daroch
- School of Environment and Energy, Peking University Shenzhen Graduate School, Shenzhen 518055, China; (M.L.); (M.D.)
| | - Jie Tang
- Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu 610106, China; (D.Y.); (L.D.)
- Correspondence: ; Tel.: +86-028-84616063
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39
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Ferragut Cardoso AP, Banerjee M, Nail AN, Lykoudi A, States JC. miRNA dysregulation is an emerging modulator of genomic instability. Semin Cancer Biol 2021; 76:120-131. [PMID: 33979676 PMCID: PMC8576067 DOI: 10.1016/j.semcancer.2021.05.004] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 04/30/2021] [Accepted: 05/03/2021] [Indexed: 12/12/2022]
Abstract
Genomic instability consists of a range of genetic alterations within the genome that contributes to tumor heterogeneity and drug resistance. It is a well-established characteristic of most cancer cells. Genome instability induction results from defects in DNA damage surveillance mechanisms, mitotic checkpoints and DNA repair machinery. Accumulation of genetic alterations ultimately sets cells towards malignant transformation. Recent studies suggest that miRNAs are key players in mediating genome instability. miRNAs are a class of small RNAs expressed in most somatic tissues and are part of the epigenome. Importantly, in many cancers, miRNA expression is dysregulated. Consequently, this review examines the role of miRNA dysregulation as a causal step for induction of genome instability and subsequent carcinogenesis. We focus specifically on mechanistic studies assessing miRNA(s) and specific subtypes of genome instability or known modes of genome instability. In addition, we provide insight on the existing knowledge gaps within the field and possible ways to address them.
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Affiliation(s)
- Ana P Ferragut Cardoso
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, 40202, USA
| | - Mayukh Banerjee
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, 40202, USA
| | - Alexandra N Nail
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, 40202, USA
| | - Angeliki Lykoudi
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, 40202, USA
| | - J Christopher States
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, 40202, USA.
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40
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Tian HF, Hu QM, Li Z. Genome-wide identification of simple sequence repeats and development of polymorphic SSR markers in swamp eel (Monopterus albus). Sci Prog 2021; 104:368504211035597. [PMID: 34375541 PMCID: PMC10358632 DOI: 10.1177/00368504211035597] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Swamp eel is one model species for sexual reversion and an aquaculture fish in China. One local strain with deep yellow and big spots of Monopterus albus has been selected for consecutive selective breeding. The objectives of this study were characterizing the Simple Sequence Repeats (SSRs) of M. albus in the assembled genome obtained recently, and developing polymorphic SSRs for future breeding programs. METHODS The genome wide SSRs were mined by using MISA software, and their types and genomic distribution patterns were investigated. Based on the available flanking sequences, primer pairs were batched developed, and Polymorphic SSRs were identified by using Polymorphic SSR Retrieval tool. The obtained polymorphic SSRs were validated by using e-PCR and capillary electrophoresis, then they were used to investigate genetic diversity of one breeding population. RESULTS A total of 364,802 SSRs were identified in assembled M. albus genome. The total length, density and frequency of SSRs were 8,204,641 bp, 10,259 bp/Mb, and 456.16 loci/Mb, respectively. Mononucleotide repeats were predominant among SSRs (33.33%), and AC and AAT repeats were the most abundant di- and tri-nucleotide repeats motifs. A total of 287,189 primer pairs were designed, and a high-density physical map was constructed (359.11 markers per Mb). A total of 871 polymorphic SSRs were identified, and 38 SSRs of 101 randomly selected ones were validated by using e-PCR and capillary electrophoresis. Using these 38 polymorphic SSRs, 201 alleles were detected and genetic diversity level (Na, PIC, HO, and He) was evaluated. CONCLUSIONS The genome-wide SSRs and newly developed SSR markers will provide a useful tool for genetic mapping, diversity analysis studies in swamp eel in the future. The high level of genetic diversity (Na = 5.29, PIC = 0.5068, HO = 0.4665, He = 0.5525) but excess of homozygotes (FIS = 0.155) in one breeding population provide baseline information for future breeding program.
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Affiliation(s)
- Hai-feng Tian
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, Hubei, China
| | - Qiao-mu Hu
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, Hubei, China
| | - Zhong Li
- Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, Hubei, China
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41
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Lei Y, Zhou Y, Price M, Song Z. Genome-wide characterization of microsatellite DNA in fishes: survey and analysis of their abundance and frequency in genome-specific regions. BMC Genomics 2021; 22:421. [PMID: 34098869 PMCID: PMC8186053 DOI: 10.1186/s12864-021-07752-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 05/24/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Microsatellite repeats are ubiquitous in organism genomes and play an important role in the chromatin organization, regulation of gene activity, recombination and DNA replication. Although microsatellite distribution patterns have been studied in most phylogenetic lineages, they are unclear in fish species. RESULTS Here, we present the first systematic examination of microsatellite distribution in coding and non-coding regions of 14 fish genomes. Our study showed that the number and type of microsatellites displayed nonrandom distribution for both intragenic and intergenic regions, suggesting that they have potential roles in transcriptional or translational regulation and DNA replication slippage theories alone were insufficient to explain the distribution patterns. Our results showed that microsatellites are dominant in non-coding regions. The total number of microsatellites ranged from 78,378 to 1,012,084, and the relative density varied from 4925.76 bp/Mb to 25,401.97 bp/Mb. Overall, (A + T)-rich repeats were dominant. The dependence of repeat abundance on the length of the repeated unit (1-6 nt) showed a great similarity decrease, whereas more tri-nucleotide repeats were found in exonic regions than tetra-nucleotide repeats of most species. Moreover, the incidence of different repeated types appeared species- and genomic-specific. These results highlight potential mechanisms for maintaining microsatellite distribution, such as selective forces and mismatch repair systems. CONCLUSIONS Our data could be beneficial for the studies of genome evolution and microsatellite DNA evolutionary dynamics, and facilitate the exploration of microsatellites structural, function, composition mode and molecular markers development in these species.
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Affiliation(s)
- Yi Lei
- Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, 610065, People's Republic of China
| | - Yu Zhou
- Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, 610065, People's Republic of China
| | - Megan Price
- Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, 610065, People's Republic of China
| | - Zhaobin Song
- Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, College of Life Sciences, Sichuan University, Chengdu, 610065, People's Republic of China.
- Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, People's Republic of China.
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42
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Gharesouran J, Hosseinzadeh H, Ghafouri-Fard S, Taheri M, Rezazadeh M. STRs: Ancient Architectures of the Genome beyond the Sequence. J Mol Neurosci 2021; 71:2441-2455. [PMID: 34056692 DOI: 10.1007/s12031-021-01850-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 04/22/2021] [Indexed: 01/24/2023]
Abstract
Short tandem repeats (STRs) are commonly defined as short runs of repetitive nucleotides, consisting of tandemly repeating 2-6- bp motif units, which are ubiquitously distributed throughout genomes. Functional STRs are polymorphic in the population, and their variations influence gene expression, which subsequently may result in pathogenic phenotypes. To understand STR phenotypic effects and their functional roles, we describe four different mutational mechanisms including the unequal crossing-over model, gene conversion, retrotransposition mechanism and replication slippage. Due to the multi-allelic nature, small length, abundance, high variability, codominant inheritance, nearly neutral evolution, extensive genome coverage and simple assaying of STRs, these markers are widely used in various types of biological research, including population genetics studies, genome mapping, molecular epidemiology, paternity analysis and gene flow studies. In this review, we focus on the current knowledge regarding STR genomic distribution, function, mutation and applications.
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Affiliation(s)
- Jalal Gharesouran
- Molecular Genetics Division, GMG center, Tabriz, Iran.,Division of Medical Genetics, Tabriz Childrens Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hassan Hosseinzadeh
- Molecular Genetics Division, GMG center, Tabriz, Iran.,Division of Medical Genetics, Tabriz Childrens Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Maryam Rezazadeh
- Division of Medical Genetics, Tabriz Childrens Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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43
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Thakur J, Packiaraj J, Henikoff S. Sequence, Chromatin and Evolution of Satellite DNA. Int J Mol Sci 2021; 22:ijms22094309. [PMID: 33919233 PMCID: PMC8122249 DOI: 10.3390/ijms22094309] [Citation(s) in RCA: 108] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 04/16/2021] [Accepted: 04/17/2021] [Indexed: 12/15/2022] Open
Abstract
Satellite DNA consists of abundant tandem repeats that play important roles in cellular processes, including chromosome segregation, genome organization and chromosome end protection. Most satellite DNA repeat units are either of nucleosomal length or 5–10 bp long and occupy centromeric, pericentromeric or telomeric regions. Due to high repetitiveness, satellite DNA sequences have largely been absent from genome assemblies. Although few conserved satellite-specific sequence motifs have been identified, DNA curvature, dyad symmetries and inverted repeats are features of various satellite DNAs in several organisms. Satellite DNA sequences are either embedded in highly compact gene-poor heterochromatin or specialized chromatin that is distinct from euchromatin. Nevertheless, some satellite DNAs are transcribed into non-coding RNAs that may play important roles in satellite DNA function. Intriguingly, satellite DNAs are among the most rapidly evolving genomic elements, such that a large fraction is species-specific in most organisms. Here we describe the different classes of satellite DNA sequences, their satellite-specific chromatin features, and how these features may contribute to satellite DNA biology and evolution. We also discuss how the evolution of functional satellite DNA classes may contribute to speciation in plants and animals.
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Affiliation(s)
- Jitendra Thakur
- Department of Biology, Emory University, Atlanta, GA 30322, USA;
- Correspondence:
| | - Jenika Packiaraj
- Department of Biology, Emory University, Atlanta, GA 30322, USA;
| | - Steven Henikoff
- Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA;
- Fred Hutchinson Cancer Research Center, Howard Hughes Medical Institute, Seattle, WA 98109, USA
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44
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Katsumata K, Ichikawa Y, Fuse T, Kurumizaka H, Yanagida A, Urano T, Kato H, Shimizu M. Sequence-dependent nucleosome formation in trinucleotide repeats evaluated by in vivo chemical mapping. Biochem Biophys Res Commun 2021; 556:179-184. [PMID: 33839413 DOI: 10.1016/j.bbrc.2021.03.155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 03/28/2021] [Indexed: 11/18/2022]
Abstract
Trinucleotide repeat sequences (TRSs), consisting of 10 unique classes of repeats in DNA, are members of microsatellites and abundantly and non-randomly distributed in many eukaryotic genomes. The lengths of TRSs are mutable, and the expansions of several TRSs are implicated in hereditary neurological diseases. However, the underlying causes of the biased distribution and the dynamic properties of TRSs in the genome remain elusive. Here, we examined the effects of TRSs on nucleosome formation in vivo by histone H4-S47C site-directed chemical cleavages, using well-defined yeast minichromosomes in which each of the ten TRS classes resided in the central region of a positioned nucleosome. We showed that (AAT)12 and (ACT)12 act as strong nucleosome-promoting sequences, while (AGG)12 and (CCG)12 act as nucleosome-excluding sequences in vivo. The local histone binding affinity scores support the idea that nucleosome formation in TRSs, except for (AGG)12, is mainly determined by the affinity for the histone octamers. Overall, our study presents a framework for understanding the nucleosome-forming abilities of TRSs.
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Affiliation(s)
- Koji Katsumata
- Department of Chemistry, Graduate School of Science and Engineering, Meisei University, 2-1-1 Hodokubo, Hino, Tokyo, 191-8506, Japan
| | - Yuichi Ichikawa
- Division of Cancer Biology, The Cancer Institute of JFCR, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Tomohiro Fuse
- Department of Chemistry, Graduate School of Science and Engineering, Meisei University, 2-1-1 Hodokubo, Hino, Tokyo, 191-8506, Japan
| | - Hitoshi Kurumizaka
- Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan
| | - Akio Yanagida
- School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan
| | - Takeshi Urano
- Department of Biochemistry, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Hiroaki Kato
- Department of Biochemistry, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Mitsuhiro Shimizu
- Department of Chemistry, Graduate School of Science and Engineering, Meisei University, 2-1-1 Hodokubo, Hino, Tokyo, 191-8506, Japan.
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45
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Characterization of microsatellites in the endangered snow leopard based on the chromosome-level genome. MAMMAL RES 2021. [DOI: 10.1007/s13364-021-00563-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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46
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Transcriptome sequencing and microsatellite marker discovery in Ailanthus altissima (Mill.) Swingle (Simaroubaceae). Mol Biol Rep 2021; 48:2007-2023. [PMID: 33730287 DOI: 10.1007/s11033-020-05402-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 03/25/2020] [Indexed: 10/21/2022]
Abstract
Ailanthus altissima Swingle, is a tree species native to East Asia and has a great potential in decorative, bioenergy and industrial applications in many countries. To date, despite its commercial importance, the genomic and genetic resources available for this species are still insufficient. In this study, we characterized the transcriptome of A. altissima and developed thirteen EST-SSRs (expressed sequence tag-simple sequence repeats) based on Illumina paired-end RNA sequencing (RNA-seq). Besides, we developed ten polymorphic chloroplast microsatellite (cpSSR) markers using the available chloroplast genome of A. altissima. The transcriptome data produced 87,797 unigenes, of which 64,891 (73.91%) unigenes were successfully annotated in at least one protein database. For cpSSR markers the number of detected alleles (N) per marker varied from three at cpSSR12 to twelve at cpSSR8, the unbiased haploid diversity indices (uh) varied from 0.111 to 0.485, and haploid diversity indices (h) ranged from 0.101 to 0.444 with an average unbiased haploid diversity index (uh) of 0.274. Overall, a total of 65 different cpSSR alleles were identified at the ten loci among 165 individuals of A. altissima. The allele number per locus for EST-SSRs varied from 2.143 to 9.357, and the values of observed and expected heterozygosity ranged from 0.312 to 1.000 and 0.505 to 0.826, respectively. The molecular markers developed in this study will facilitate future genetic diversity, population structure, long distance-gene transfer and pollen-based gene flow analyses of A. altissima populations from its known distribution ranges in China focusing on planted and natural forest stands.
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47
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Podder A, Lee HJ, Kim BH. Fluorescent Nucleic Acid Systems for Biosensors. BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 2021. [DOI: 10.1246/bcsj.20200351] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Arup Podder
- Department of Chemistry, Division of Advanced Materials Science, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea
| | - Ha Jung Lee
- Department of Chemistry, Division of Advanced Materials Science, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea
| | - Byeang Hyean Kim
- Department of Chemistry, Division of Advanced Materials Science, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea
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48
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Annear DJ, Vandeweyer G, Elinck E, Sanchis-Juan A, French CE, Raymond L, Kooy RF. Abundancy of polymorphic CGG repeats in the human genome suggest a broad involvement in neurological disease. Sci Rep 2021; 11:2515. [PMID: 33510257 PMCID: PMC7844047 DOI: 10.1038/s41598-021-82050-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 12/29/2020] [Indexed: 11/09/2022] Open
Abstract
Expanded CGG-repeats have been linked to neurodevelopmental and neurodegenerative disorders, including the fragile X syndrome and fragile X-associated tremor/ataxia syndrome (FXTAS). We hypothesized that as of yet uncharacterised CGG-repeat expansions within the genome contribute to human disease. To catalogue the CGG-repeats, 544 human whole genomes were analyzed. In total, 6101 unique CGG-repeats were detected of which more than 93% were highly variable in repeat length. Repeats with a median size of 12 repeat units or more were always polymorphic but shorter repeats were often polymorphic, suggesting a potential intergenerational instability of the CGG region even for repeats units with a median length of four or less. 410 of the CGG repeats were associated with known neurodevelopmental disease genes or with strong candidate genes. Based on their frequency and genomic location, CGG repeats may thus be a currently overlooked cause of human disease.
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Affiliation(s)
- Dale J Annear
- Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
| | - Geert Vandeweyer
- Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
| | - Ellen Elinck
- Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
| | - Alba Sanchis-Juan
- NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.,Department of Haematology, NHS Blood and Transplant Centre, University of Cambridge, Cambridge, CB2 0PT, UK
| | - Courtney E French
- Department of Paediatrics, University of Cambridge, Cambridge, CB2 0QQ, UK
| | - Lucy Raymond
- NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.,Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK
| | - R Frank Kooy
- Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
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Singh P, Nath R, Venkatesh V. Comparative Genome-Wide Characterization of Microsatellites in Candida albicans and Candida dubliniensis Leading to the Development of Species-Specific Marker. Public Health Genomics 2021; 24:1-13. [PMID: 33401274 DOI: 10.1159/000512087] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 09/30/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Microsatellites or simple sequence repeats (SSR) are related to genomic structure, function, and certain diseases of taxonomically different organisms. OBJECTIVE To characterize microsatellites in two closely related Candida species by searching and comparing 1-6 bp nucleotide motifs and utilizing them to develop species-specific markers. METHODS Whole-genome sequence was downloaded from the public domain, microsatellites were mined and analyzed, and primers were synthesized. RESULTS A total of 15,821 and 7,868 microsatellites, with mono-nucleotides (8,679) and trinucleotides (3,156) as most frequent microsatellites, were mined in Candida dubliniensis and Candida albicans, respectively. Chromosome size was found positively correlated with microsatellite number in both the species, whereas it was negatively correlated with the relative abundance and density of microsatellites. A number of unique motifs were also found in both the species. Overall, microsatellite frequencies of each chromosome in C. dubliniensis were higher than in C. albicans. CONCLUSION The features of microsatellite distribution in the two species' genomes revealed that it is probably not conserved in the genus Candida. Data generated in this article could be used for comparative genome mapping and understanding the distribution of microsatellites and genome structure between these closely related and phenotypically misidentified species and may provide a foundation for the development of a new set of species-specific microsatellite markers. Here, we also report a novel microsatellite-based marker for C. dubliniensis-specific identification.
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Affiliation(s)
- Pallavi Singh
- Department of Biotechnology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow, India, .,Department of Computer Science & Engineering, UIET, CSJM University, Kanpur, India,
| | - Ravindra Nath
- Department of Computer Science & Engineering, UIET, CSJM University, Kanpur, India
| | - Vimala Venkatesh
- Department of Microbiology, King George's Medical University, Lucknow, India
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50
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Ahmad SF, Singchat W, Jehangir M, Suntronpong A, Panthum T, Malaivijitnond S, Srikulnath K. Dark Matter of Primate Genomes: Satellite DNA Repeats and Their Evolutionary Dynamics. Cells 2020; 9:E2714. [PMID: 33352976 PMCID: PMC7767330 DOI: 10.3390/cells9122714] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/15/2020] [Accepted: 12/16/2020] [Indexed: 12/12/2022] Open
Abstract
A substantial portion of the primate genome is composed of non-coding regions, so-called "dark matter", which includes an abundance of tandemly repeated sequences called satellite DNA. Collectively known as the satellitome, this genomic component offers exciting evolutionary insights into aspects of primate genome biology that raise new questions and challenge existing paradigms. A complete human reference genome was recently reported with telomere-to-telomere human X chromosome assembly that resolved hundreds of dark regions, encompassing a 3.1 Mb centromeric satellite array that had not been identified previously. With the recent exponential increase in the availability of primate genomes, and the development of modern genomic and bioinformatics tools, extensive growth in our knowledge concerning the structure, function, and evolution of satellite elements is expected. The current state of knowledge on this topic is summarized, highlighting various types of primate-specific satellite repeats to compare their proportions across diverse lineages. Inter- and intraspecific variation of satellite repeats in the primate genome are reviewed. The functional significance of these sequences is discussed by describing how the transcriptional activity of satellite repeats can affect gene expression during different cellular processes. Sex-linked satellites are outlined, together with their respective genomic organization. Mechanisms are proposed whereby satellite repeats might have emerged as novel sequences during different evolutionary phases. Finally, the main challenges that hinder the detection of satellite DNA are outlined and an overview of the latest methodologies to address technological limitations is presented.
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Affiliation(s)
- Syed Farhan Ahmad
- Laboratory of Animal Cytogenetics and Comparative Genomics (ACCG), Department of Genetics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand; (S.F.A.); (W.S.); (M.J.); (A.S.); (T.P.)
- Special Research Unit for Wildlife Genomics (SRUWG), Department of Forest Biology, Faculty of Forestry, Kasetsart University, Bangkok 10900, Thailand
| | - Worapong Singchat
- Laboratory of Animal Cytogenetics and Comparative Genomics (ACCG), Department of Genetics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand; (S.F.A.); (W.S.); (M.J.); (A.S.); (T.P.)
- Special Research Unit for Wildlife Genomics (SRUWG), Department of Forest Biology, Faculty of Forestry, Kasetsart University, Bangkok 10900, Thailand
| | - Maryam Jehangir
- Laboratory of Animal Cytogenetics and Comparative Genomics (ACCG), Department of Genetics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand; (S.F.A.); (W.S.); (M.J.); (A.S.); (T.P.)
- Department of Structural and Functional Biology, Institute of Bioscience at Botucatu, São Paulo State University (UNESP), Botucatu, São Paulo 18618-689, Brazil
| | - Aorarat Suntronpong
- Laboratory of Animal Cytogenetics and Comparative Genomics (ACCG), Department of Genetics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand; (S.F.A.); (W.S.); (M.J.); (A.S.); (T.P.)
- Special Research Unit for Wildlife Genomics (SRUWG), Department of Forest Biology, Faculty of Forestry, Kasetsart University, Bangkok 10900, Thailand
| | - Thitipong Panthum
- Laboratory of Animal Cytogenetics and Comparative Genomics (ACCG), Department of Genetics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand; (S.F.A.); (W.S.); (M.J.); (A.S.); (T.P.)
- Special Research Unit for Wildlife Genomics (SRUWG), Department of Forest Biology, Faculty of Forestry, Kasetsart University, Bangkok 10900, Thailand
| | - Suchinda Malaivijitnond
- National Primate Research Center of Thailand, Chulalongkorn University, Saraburi 18110, Thailand;
- Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kornsorn Srikulnath
- Laboratory of Animal Cytogenetics and Comparative Genomics (ACCG), Department of Genetics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand; (S.F.A.); (W.S.); (M.J.); (A.S.); (T.P.)
- Special Research Unit for Wildlife Genomics (SRUWG), Department of Forest Biology, Faculty of Forestry, Kasetsart University, Bangkok 10900, Thailand
- National Primate Research Center of Thailand, Chulalongkorn University, Saraburi 18110, Thailand;
- Center of Excellence on Agricultural Biotechnology (AG-BIO/PERDO-CHE), Bangkok 10900, Thailand
- Omics Center for Agriculture, Bioresources, Food and Health, Kasetsart University (OmiKU), Bangkok 10900, Thailand
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