Article
Genetics & Heredity
Andre E. Minoche, Ben Lundie, Greg B. Peters, Thomas Ohnesorg, Mark Pinese, David M. Thomas, Andreas Zankl, Tony Roscioli, Nicole Schonrock, Sarah Kummerfeld, Leslie Burnett, Marcel E. Dinger, Mark J. Cowley
Summary: ClinSV is a WGS-based framework for integration, annotation, prioritization, and visualization of structural variants with low false positive rates and high reproducibility. In clinical practice, ClinSV identified reportable variants that were undetectable by current clinical microarray designs in a significant percentage of cases.
Article
Oncology
Kris G. Samsom, Luuk J. Schipper, Paul Roepman, Linda J. W. Bosch, Ferry Lalezari, Elisabeth G. Klompenhouwer, Adrianus J. de Langen, Tineke E. Buffart, Immy Riethorst, Lieke Schoenmaker, Daoin Schout, Vincent van der Noort, Jose G. van den Berg, Ewart de Bruijn, Jacobus J. M. van der Hoeven, Hans van Snellenberg, Lizet E. van der Kolk, Edwin Cuppen, Emile E. Voest, Gerrit A. Meijer, Kim Monkhorst
Summary: This study aimed to evaluate the feasibility and efficacy of whole-genome sequencing (WGS) in routine clinical practice. The results showed that WGS can be successfully applied to patients with metastatic cancer, providing comprehensive genomic profiling for the majority of patients and identifying actionable biomarkers and treatment options.
JOURNAL OF PATHOLOGY
(2022)
Review
Microbiology
Matus Dohal, Igor Porvaznik, Ivan Solovic, Juraj Mokry
Summary: Infections caused by non-tuberculous mycobacteria (NTM) are a growing public health concern. Traditional diagnostic tests lack sufficient specificity, but whole genome sequencing (WGS) has emerged as a crucial tool for identifying new species and gene mutations in clinical practice.
Article
Biochemistry & Molecular Biology
Filipe Cortes-Figueiredo, Filipa S. Carvalho, Ana Catarina Fonseca, Friedemann Paul, Jose M. Ferro, Sebastian Schoenherr, Hansi Weissensteiner, Vanessa A. Morais
Summary: Despite the various methods available for mtDNA sample preparation, sequencing, and data analysis, there is still a need for innovation compared to nDNA research. The Precision ID mtDNA Whole Genome Panel by Applied Biosystems is a novel library preparation kit suitable for degraded samples and low DNA input, however, its bioinformatic processing occurs in Ion Torrent Suite Software, producing BAM files aligned to an unorthodox version of rCRS with a heteroplasmy threshold of 10%. A customizable pipeline called PrecisionCallerPipeline (PCP) was presented in this study for processing samples correctly after Ion Torrent sequencing with the Precision ID library kit, achieving improved performance metrics compared to the proprietary software, with optimal performance at a 2.5% heteroplasmy threshold.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ying Ni, Xudong Liu, Zemenu Mengistie Simeneh, Mengsu Yang, Runsheng Li
Summary: This study evaluates the application of the recently released R10.4 flow cell from Oxford Nanopore Technologies in human cancer genomics and epigenomic research. The results show that R10.4 performs better than R9.4.1 in terms of read accuracy, variant detection, methylation calling, and genome recovery rate. In addition, the study proposes a promising method for high-yield single-cell whole-genome amplification sequencing and provides a possible solution for filtering false positive sites using R10.4 data.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Genetics & Heredity
Jia Li, Jiaqi Lu, Fengxia Su, Jiexia Yang, Jia Ju, Yu Lin, Jinjin Xu, Yiming Qi, Yaping Hou, Jing Wu, Wei He, Zhengtao Yang, Yujing Wu, Zhuangyuan Tang, Yingping Huang, Guohong Zhang, Ying Yang, Zhou Long, Xiaofang Cheng, Ping Liu, Jun Xia, Yanyan Zhang, Yicong Wang, Fang Chen, Jianguo Zhang, Lijian Zhao, Xin Jin, Ya Gao, Aihua Yin
Summary: This study developed a method to effectively recover the whole fetal genome using maternal plasma cfDNA and parental genomic DNA sequencing data and validated its effectiveness in noninvasively detecting SNVs, insertions, and deletions. The approach showed high accuracy in predicting healthy fetuses and successfully detected pathogenic variations in fetuses with monogenic diseases.
FRONTIERS IN GENETICS
(2022)
Article
Immunology
Serisha D. Naicker, Tsidiso G. Maphanga, Nancy A. Chow, Mushal Allam, Stanford Kwenda, Arshad Ismail, Nelesh P. Govender
Summary: The study identified different clades of C. auris isolates in South Africa, confirming introductions from South Asia followed by local transmission, while also indicating early introductions from other regions.
EMERGING MICROBES & INFECTIONS
(2021)
Article
Multidisciplinary Sciences
Veronica Gonzalez-Pena, Sivaraman Natarajan, Yuntao Xia, David Klein, Robert Carter, Yakun Pang, Bridget Shaner, Kavya Annu, Daniel Putnam, Wenan Chen, Jon Connelly, Shondra Pruett-Miller, Xiang Chen, John Easton, Charles Gawad
Summary: Primary template-directed amplification (PTA) is an isothermal whole genome amplification method that accurately captures over 95% of single cell genomes, improving variant detection sensitivity and precision. By utilizing PTA, studies such as direct measurement of environmental mutagenicity (DMEM) and genome-wide off-target detection post CRISPR-mediated editing in single cells become feasible. PTA overcomes the current limitations of accurate WGA, enabling research on genetic diversity and evolution at cellular resolution.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Gastroenterology & Hepatology
Lauren Collen, David Y. Kim, Michael Field, Ibeawuchi Okoroafor, Gwen Saccocia, Sydney Driscoll Whitcomb, Julia Green, Michelle Dao Dong, Jared Barends, Bridget Carey, Madison E. Weatherly, Shira Rockowitz, Piotr Sliz, Enju Liu, Alal Eran, Leslie Grushkin-Lerner, Athos Bousvaros, Aleixo M. Muise, Christoph Klein, Vanessa Mitsialis, Jodie Ouahed, Scott B. Snapper
Summary: This study aims to observe the clinical phenotypes and outcomes of VEOIBD patients, and it finds that monogenic disease is an important driver of disease severity in VEOIBD. Whole exome sequencing (WES) is a valuable tool in prognostication and management of VEOIBD.
JOURNAL OF CROHNS & COLITIS
(2022)
Article
Genetics & Heredity
Xiufang Zhi, Qi Ai, Wenchao Sheng, Yuping Yu, Jianbo Shu, Changshun Yu, Xiaoli Yu, Dong Li, Chunquan Cai
Summary: This study investigated the clinical characteristics and molecular basis of a patient with Menkes disease. The patient exhibited symptoms such as intermittent convulsions and psychomotor retardation, and a novel deep intronic variant in the ATP7A gene was identified through whole genome sequencing. Additionally, RNA sequencing confirmed the functional effect of this variant.
FRONTIERS IN GENETICS
(2022)
Article
Chemistry, Multidisciplinary
Kun Yin, Shanqing Huang, Weidong Ruan, Haopai Wei, He Dong, Dianyi Liang, Meijuan Zhao, Wei Qi, Chaoyong Yang, Zhi Zhu
Summary: Iso-seq is a rapid and uniform single-cell whole-genome sequencing method that uses a specially designed dual-well structure and a capillary-based centrifugal-driven droplet generator to isolate single cells and compartmentalize their genomes in droplets within 3 minutes. Iso-seq achieves high mapping ratio, broad coverage of the genome, and low coefficient of variation, making it promising for a wide variety of biological applications.
Article
Rheumatology
Can Kosukcu, Ekim Z. Taskiran, Ezgi Deniz Batu, Erdal Sag, Yelda Bilginer, Mehmet Alikasifoglu, Seza Ozen
Summary: In this study, phenotype-genotype correlations in unclassified autoinflammatory disease (AID) patients were investigated using whole exome sequencing (WES), revealing disease-causing genetic variants in a subset of patients. The WES strategy proved to be cost-effective and yielded substantial results for the undefined AID patients, contributing to the understanding of the spectrum of unclassified AIDs.
Article
Pathology
Katherine A. Lau, Anders Goncalves da Silva, Torsten Theis, Joanna Gray, Susan A. Ballard, William D. Rawlinson
Summary: The widespread adoption of whole genome sequencing (WGS) data for pathogen surveillance and infectious disease decision-making requires ensuring data quality standards are met for accurate identification and monitoring of pathogens. The development of a pilot proficiency testing program helps establish baseline guidelines for standardization of WGS data and facilitates accreditation of test processes through ongoing performance benchmarking.
Article
Genetics & Heredity
Kushani Jayasinghe, Zornitza Stark, Peter G. Kerr, Clara Gaff, Melissa Martyn, John Whitlam, Belinda Creighton, Elizabeth Donaldson, Matthew Hunter, Anna Jarmolowicz, Lilian Johnstone, Emma Krzesinski, Sebastian Lunke, Elly Lynch, Kathleen Nicholls, Chirag Patel, Yael Prawer, Jessica Ryan, Emily J. See, Andrew Talbot, Alison Trainer, Rigan Tytherleigh, Giulia Valente, Mathew Wallis, Louise Wardrop, Kirsty H. West, Susan M. White, Ella Wilkins, Andrew J. Mallett, Catherine Quinlan
Summary: In a cohort of patients with suspected monogenic kidney disease in Australia, exome sequencing (ES) had a high diagnostic yield and clinical impact. The study identified predictors of positive diagnosis and highlighted the potential benefits of using ES in guiding clinical practice and health service design.
GENETICS IN MEDICINE
(2021)
Article
Genetics & Heredity
Ulykbek Kairov, Askhat Molkenov, Aigul Sharip, Saule Rakhimova, Madina Seidualy, Arang Rhie, Ulan Kozhamkulov, Maxat Zhabagin, Jong-Il Kim, Joseph H. Lee, Joseph D. Terwilliger, Jeong-Sun Seo, Zhaxybay Zhumadilov, Ainur Akilzhanova
Summary: Kazakhstan, located along the Great Silk Road, has a rich history and a multiethnic population. By sequencing and analyzing the genomes of five ethnic Kazakhs, this study identified genetic variants associated with higher risks of diseases and demonstrated the importance of genotype-phenotype relations at the population level.
FRONTIERS IN GENETICS
(2022)
Article
Pediatrics
Kajsa Appelberg, Lene Sorensen, Rolf H. Zetterstrom, Martin Henriksson, Anna Wedell, Lars-Ake Levin
Summary: This study evaluates the long-term costs and health effects of the Swedish newborn screening program for classic phenylketonuria (PKU) alone and in combination with congenital hypothyroidism (CH) compared with no screening. Screening for PKU plus CH was found to be more effective and less costly compared with other strategies, resulting in substantial cost savings for society while generating additional quality-adjusted life-years (QALYs). These findings highlight the importance of public investments in early diagnosis and treatment.
JOURNAL OF PEDIATRICS
(2023)
Article
Endocrinology & Metabolism
Anna Gunnerbeck, Cecilia Lundholm, Ulrika von Dobeln, Rolf H. Zetterstrom, Catarina Almqvist, Anna Nordenstrom
Summary: This study evaluated the neonatal screening and diagnosis of congenital hypothyroidism (CH) and found that 50% of children diagnosed with CH were not detected in the screening. The incidence of screening positive CH increased and screening negative CH decreased after lowering the TSH screening threshold. Screening negative CH was associated with female sex, twinning, prematurity, low birth weight, birth defects, and need for neonatal intensive care.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Dominyka Batkovskyte, Fiona McKenzie, Fulya Taylan, Pelin Ozlem Simsek-Kiper, Sarah M. Nikkel, Hirofumi Ohashi, Roger E. Stevenson, Thuong Ha, Denise P. Cavalcanti, Hiroyuki Miyahara, Steven A. Skinner, Miguel A. Aguirre, Zuehal Akcoeren, Gulen Eda Utine, Tillie Chiu, Kenji Shimizu, Anna Hammarsjoe, Koray Boduroglu, Hannah W. Moore, Raymond J. Louie, Peer Arts, Allie N. Merrihew, Milena Babic, Matilda R. Jackson, Nikos Papadogiannakis, Anna Lindstrand, Ann Nordgren, Christopher P. Barnett, Hamish S. Scott, Andrei S. Chagin, Gen Nishimura, Giedre Grigelioniene
Summary: Lethal short-limb skeletal dysplasia Al-Gazali type is a rare disorder with unknown genetic etiology. A study involving nine patients with clinical features consistent with this disorder identified disease-causing variants in ADAMTSL2, shedding light on the genetic cause and highlighting the importance of analyzing the pseudogene region. This study enhances our understanding of Al-Gazali skeletal dysplasia and its association with ADAMTSL2-related disorders.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Medicine, General & Internal
Maribel Aranda-Guillen, Ellen Christine Royrvik, Sara Fletcher-Sandersjoo, Haydee Artaza, Ileana Ruxandra Botusan, Marianne A. Grytaas, Asa Hallgren, Lars Breivik, Maria Pettersson, Anders P. Jorgensen, Anna Lindstrand, Elinor Vogt, Eystein S. Husebye, Olle Kampe, Anette S. Boe Wolff, Sophie Bensing, Stefan Johansson, Daniel Eriksson
Summary: By constructing and evaluating a polygenic risk score (PRS) for autoimmune Addison's disease (AAD), the study explores the pathogenesis of primary adrenal insufficiency (PAI) in pediatric patients. The PRS can effectively differentiate cases from controls and estimate susceptibility in individual patients. The PRS shows promise as a clinical tool to detect disease etiologies other than autoimmunity.
JOURNAL OF INTERNAL MEDICINE
(2023)
Review
Medicine, General & Internal
Bianca Tesi, Catherine Boileau, Kym M. Boycott, Guillaume Canaud, Mark Caulfield, Daniela Choukair, Sue Hill, Malte Spielmann, Anna Wedell, Valtteri Wirta, Ann Nordgren, Anna Lindstrand
Summary: Molecular diagnostics plays a crucial role in tailoring individual treatment and care based on molecular data. Genome sequencing (GS) is emerging as the primary method for precision diagnostics in rare diseases, due to its improved diagnostic yield and ability to detect a broad range of genetic aberrations. By integrating precision medicine into clinical practice, GS can accelerate targeted drug development and improve patient management in rare diseases.
JOURNAL OF INTERNAL MEDICINE
(2023)
Article
Genetics & Heredity
Monika K. Grudzinska Pechhacker, Anna Molnar, Nadja Pekkola Pacheco, Hakan Thonberg, Laurence Querat, Ulrika Birkeldh, Ann Nordgren, Anna Lindstrand
Summary: This study presents a family with a milder phenotype of SCLT1-related disease, characterized by ADHD, obesity, mild photophobia, and various ophthalmologic abnormalities. Genetic testing revealed a likely pathogenic variant in the SCLT1 gene. The study highlights the importance of comprehensive diagnostics in patients with reduced vision, refractive errors, and ADHD spectrum disorders.
OPHTHALMIC GENETICS
(2023)
Article
Pediatrics
Ann Nordgren, Anna Lindstrand, Hsi-Yang Wu, Magdalena Fossum
Summary: Precision Medicine has the potential to address specific phenotypes of common diseases and uncover risk factors and pathogenesis of rare diseases. Professors Ann Nordgren and Anna Lindstrand discuss the Swedish national project on Precision Medicine and its impact on pediatric urology care.
JOURNAL OF PEDIATRIC UROLOGY
(2023)
Article
Multidisciplinary Sciences
Hannes Runheim, Maria Pettersson, Anna Hammarsjo, Ann Nordgren, Martin Henriksson, Anna Lindstrand, Lars-Ake Levin, Maria Johansson Soller
Summary: Whole genome sequencing (WGS) has the potential to be a comprehensive genetic test for individuals with neurodevelopmental disorders, syndromes and congenital malformations. This study compared the healthcare costs and diagnostic yield of WGS and chromosomal microarray analysis (CMA) as the first-line genetic tests. The results showed that WGS had statistically non-significant lower costs and higher diagnostic yield compared to CMA, indicating its potential as a preferred diagnostic test.
SCIENTIFIC REPORTS
(2023)
Article
Clinical Neurology
Marlene Ek, Daniel Nilsson, Martin Engvall, Helena Malmgren, Hakan Thonberg, Maria Pettersson, Britt-Marie Anderlid, Anna Hammarsjo, Hafdis T. Helgadottir, Snjolaug Arnardottir, Karin Naess, Inger Nennesmo, Martin Paucar, Helgi Thor Hjartarson, Rayomand Press, Goran Solders, Thomas Sejersen, Anna Lindstrand, Malin Kvarnung
Summary: A study analyzed 861 patients with neuromuscular disorders using genome sequencing and comprehensive variant calling. Pathogenic variants were found in 27% of the patients, with short tandem repeat expansions and structural variants accounting for one-third of the cases. The study highlights the importance of including STR and SV analyses in the diagnostics of neuromuscular disorders.
FRONTIERS IN NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Kristine Bilgrav Saether, Daniel Nilsson, Hakan Thonberg, Emma Tham, Adam Ameur, Jesper Eisfeldt, Anna Lindstrand
Summary: The majority of rare diseases are genetic, and despite advances in genomics-based investigations, a large percentage of patients remain undiagnosed. A significant contributing factor to this is the limited understanding of transposable elements (TE), which make up a substantial portion of the human genome. This study aims to bridge this knowledge gap by characterizing TE insertions in different populations and highlights the potential clinical implications in rare disease diagnostics.
Article
Neurosciences
Raquel Vaz, Steven Edwards, Alfredo Duenas-Rey, Wolfgang Hofmeister, Anna Lindstrand
Summary: Heterozygous loss of CTNND2 gene is associated with neurodevelopmental disorders such as autism, schizophrenia, and intellectual disability. The CTNND2 gene is located on the short arm of chromosome 5, which is deleted in Cri-du-chat syndrome patients. In zebrafish, the loss of ctnnd2b leads to disorganization of neuronal subtypes in the forebrain and increased swimming activity.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Immunology
Christofer Ang, Rolf H. Zetterstrom, Kim Ramme, Emma Axelsen, Per Marits, Mikael Sundin
Summary: This report presents a case of severe combined immunodeficiency (SCID) that could have been missed in worldwide newborn screening. The patient's clinical symptoms were consistent with the immunologic workup and genetic result, providing further insights into this rare and serious disease.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Genetics & Heredity
Ela Curic, Lisa Ewans, Ryan Pysar, Fulya Taylan, Lorenzo D. Botto, Ann Nordgren, William Gahl, Elizabeth Emma Palmer
Summary: This article reviews the published literature on Undiagnosed Diseases Programs worldwide and evaluates the diagnostic and research process. The study finds that Undiagnosed Diseases Programs have potential in research diagnostics, allowing for more in-depth diagnostic approaches using research-grade bioinformatics tools and multi-omics technologies. However, due to different enrollment criteria and reporting processes, it is challenging to compare the diagnostic yield across studies. Further comparisons and exploration of Undiagnosed Diseases Programs worldwide are needed to improve their value and utility.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Fulya Taylan, Carolina Maya Gonzalez, Behzad Khoshnood, Tessa Campbell, Johan Bobeck, Yenan Bryceson, Magnus Nordenskjold, Ann Nordgren
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)