Read by QxMD icon Read

Clinical whole genome sequencing

Amber Hilliard, Dara Leong, Amy O'Callaghan, Eamonn P Culligan, Ciara A Morgan, Niall DeLappe, Colin Hill, Kieran Jordan, Martin Cormican, Cormac G M Gahan
Listeria monocytogenes is a major human foodborne pathogen that is prevalent in the natural environment and has a high case fatality rate. Whole genome sequencing (WGS) analysis has emerged as a valuable methodology for the classification of L. monocytogenes isolates and the identification of virulence islands that may influence infectivity. In this study, WGS was used to provide an insight into 25 L. monocytogenes isolates from cases of clinical infection in Ireland between 2013 and 2015. Clinical strains were either lineage I (14 isolates) or lineage II (11 isolates), with 12 clonal complexes (CC) represented, of which CC1 (6) and CC101 (4) were the most common...
March 20, 2018: Genes
Abhinav Jain, Shrey Gandhi, Remya Koshy, Vinod Scaria
Incidental findings in genomic data have been studied in great detail in the recent years, especially from population-scale data sets. However, little is known about the frequency of such findings in ethnic groups, specifically the Middle East, which were not previously covered in global sequencing studies. The availability of whole exome and genome data sets for a highly consanguineous Arab population from Qatar motivated us to explore the incidental findings in this population-scale data. The sequence data of 1005 Qatari individuals were systematically analyzed for incidental genetic variants in the 59 genes suggested by the American College of Medical Genetics and Genomics...
March 20, 2018: Molecular Genetics and Genomics: MGG
Hessa S Alsaif, Arif O Khan, Nisha Patel, Hisham Alkuraya, Mais Hashem, Firdous Abdulwahab, Niema Ibrahim, Mohammed A Aldahmesh, Fowzan S Alkuraya
Primary congenital glaucoma is a trabecular meshwork dysgenesis with resultant increased intraocular pressure and ocular damage. CYP1B1 mutations remain the most common identifiable genetic cause. However, important questions about the penetrance of CYP1B1-related congenital glaucoma remain unanswered. Furthermore, mutations in other genes have been described although their exact contribution and potential genetic interaction, if any, with CYP1B1 mutations are not fully explored. In this study, we employed modern genomic approaches to re-examine CYP1B1-related congenital glaucoma...
March 19, 2018: Human Genetics
Gopal R Gopinath, Hannah R Chase, Jayanthi Gangiredla, Athmanya Eshwar, Hyein Jang, Isha Patel, Flavia Negrete, Samantha Finkelstein, Eunbi Park, TaeJung Chung, YeonJoo Yoo, JungHa Woo, YouYoung Lee, Jihyeon Park, Hyerim Choi, Seungeun Jeong, Soyoung Jun, Mijeong Kim, Chaeyoon Lee, HyeJin Jeong, Séamus Fanning, Roger Stephan, Carol Iversen, Felix Reich, Günter Klein, Angelika Lehner, Ben D Tall
Background: Malonate utilization, an important differential trait, well recognized as being possessed by six of the seven Cronobacter species is thought to be largely absent in Cronobacter sakazakii (Csak). The current study provides experimental evidence that confirms the presence of a malonate utilization operon in 24 strains of sequence type (ST) 64, obtained from Europe, Middle East, China, and USA; it offers explanations regarding the genomic diversity and phylogenetic relatedness among these strains, and that of other C...
2018: Gut Pathogens
V Pillonel, D Juskevicius, C K Y Ng, A Bodmer, A Zettl, D Jucker, S Dirnhofer, A Tzankov
Nodal marginal zone lymphoma (NMZL) is a rare small B-cell lymphoma lacking disease-defining phenotype and precise diagnostic markers. To better understand the mutational landscape of NMZL, particularly in comparison to other nodal small B-cell lymphomas, we performed whole-exome sequencing, targeted high-throughput sequencing, and array-comparative genomic hybridization on a retrospective series. Our study identified for the first time recurrent, diagnostically useful, and potentially therapeutically relevant BRAF mutations in NMZL...
February 28, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Bradley A Perkins, C Thomas Caskey, Pamila Brar, Eric Dec, David S Karow, Andrew M Kahn, Ying-Chen Claire Hou, Naisha Shah, Debbie Boeldt, Erin Coughlin, Gabby Hands, Victor Lavrenko, James Yu, Andrea Procko, Julia Appis, Anders M Dale, Lining Guo, Thomas J Jönsson, Bryan M Wittmann, Istvan Bartha, Smriti Ramakrishnan, Axel Bernal, James B Brewer, Suzanne Brewerton, William H Biggs, Yaron Turpaz, J Craig Venter
Reducing premature mortality associated with age-related chronic diseases, such as cancer and cardiovascular disease, is an urgent priority. We report early results using genomics in combination with advanced imaging and other clinical testing to proactively screen for age-related chronic disease risk among adults. We enrolled active, symptom-free adults in a study of screening for age-related chronic diseases associated with premature mortality. In addition to personal and family medical history and other clinical testing, we obtained whole-genome sequencing (WGS), noncontrast whole-body MRI, dual-energy X-ray absorptiometry (DXA), global metabolomics, a new blood test for prediabetes (Quantose IR), echocardiography (ECHO), ECG, and cardiac rhythm monitoring to identify age-related chronic disease risks...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Justin O Szot, Hartmut Cuny, Gillian M Blue, David T Humphreys, Eddie Ip, Katrina Harrison, Gary F Sholler, Eleni Giannoulatou, Paul Leo, Emma L Duncan, Duncan B Sparrow, Joshua W K Ho, Robert M Graham, Nicholas Pachter, Gavin Chapman, David S Winlaw, Sally L Dunwoodie
BACKGROUND: Congenital heart disease (CHD)-structural abnormalities of the heart that arise during embryonic development-is the most common inborn malformation, affecting ≤1% of the population. However, currently, only a minority of cases can be explained by genetic abnormalities. The goal of this study was to identify disease-causal genetic variants in 30 families affected by CHD. METHODS: Whole-exome sequencing was performed with the DNA of multiple family members...
March 2018: Circ Genom Precis Med
Sun Shin, Hyeon-Chun Park, Min Sung Kim, Mi-Ryung Han, Sung Hak Lee, Seung Hyun Jung, Sug Hyung Lee, Yeun-Jun Chung
Anal squamous cell carcinoma (ASCC), either with human papillomavirus (HPV) (+) or (-), is a neoplastic disease with frequent recurrence and metastasis. To characterize ASCC genomes, we attempted to disclose novel alterations of ASCC genomes as well as other genetic features including mutation signatures. We performed whole-exome sequencing and copy number alteration (CNA) profiling for 8 ASCC samples from 6 patients (2 cases with primary and recurrent/metastatic tumors). We found known ASCC mutations (TP53, CDKN2A and PIK3CA) and CNAs (gains on 3q and 19q and losses on 11q and 13q)...
March 16, 2018: Human Pathology
Joan M O'Brien, Rebecca J Salowe, Raymond Fertig, Julia Salinas, Maxwell Pistilli, Prithvi S Sankar, Eydie Miller-Ellis, Amanda Lehman, Windell Murphy, Melissa Homsher, Katelyn Gordon, Gui-Shuang Ying
PURPOSE: To determine the relationship between positive family history (FH) and primary open-angle glaucoma (POAG) diagnosis and clinical presentation in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) cohort. METHODS: FH of POAG in first-degree relatives was assessed in 2365 subjects in the POAAGG cohort. A standardized interview was used to assess FH of glaucoma, demographic characteristics, lifestyle choices, and medical and ocular comorbidities...
March 16, 2018: American Journal of Ophthalmology
Aparna Prasad, Matthew A Sdano, Rena J Vanzo, Patricia A Mowery-Rushton, Moises A Serrano, Charles H Hensel, E Robert Wassman
BACKGROUND: Chromosomal microarray analysis (CMA) is recommended as the first-tier clinical diagnostic test for individuals with developmental disabilities. In addition to detecting copy number variations, CMA platforms with single nucleotide polymorphism probes can detect large homozygous regions within the genome, which represent potential risk for recessively inherited disorders. METHODS: To determine the frequency in which pathogenic or likely pathogenic variants can be detected in these regions of homozygosity, we performed whole exome sequencing (WES) in 53 individuals where homozygosity was detected by CMA...
March 20, 2018: BMC Medical Genetics
Vasiliki Rahimzadeh, Christoph Schickhardt, Bartha M Knoppers, Karine Sénécal, Danya F Vears, Conrad V Fernandez, Stefan Pfister, Sharon Plon, Sharon Terry, Janet Williams, Marc S Williams, Martina Cornel, Jan M Friedman
Accurate clinical interpretation of children's whole-genome and whole-exome sequences relies on comparing the patient's linked genomic and phenotypic data with variant reference databases of both healthy and affected patients. The robustness of such comparisons, in turn, is made possible by sharing pediatric genomic and associated clinical data. Despite this, sparse ethical-legal policy attention has been paid to making such sharing routine in practice. The interdisciplinary Paediatric Task Team of the Global Alliance for Genomics and Health considered in detail the current ethical, legal, and social implications of sharing genomic and associated clinical data involving children...
March 19, 2018: JAMA Pediatrics
Magdalena Nüesch-Inderbinen, Katrin Zurfluh, Marc J A Stevens, Roger Stephan
OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) have emerged worldwide and represent a major threat to human health. Here, we report the genome sequence of K. pneumoniae 002SK2, an NDM-9 and CTX-M-15 producing strain isolated from wastewater in Switzerland and belonging to the international high-risk clone ST147. METHODS: Whole genome sequencing of K. pneumoniae 002SK2 was performed using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) technology RS2 reads (C4/P6 chemistry)...
March 15, 2018: Journal of Global Antimicrobial Resistance
Asher Haug-Baltzell, Tushar R Bhangale, Diana Chang, Amy Dressen, Brian L Yaspan, Ward Ortmann, Matthew J Brauer, Julie Hunkapiller, Jens Reeder, Kiran Mukhyala, Karen T Cuenco, Jennifer A Tom, Amy Cowgill, Jan Vogel, William F Forrest, Timothy W Behrens, Robert R Graham, Arthur Wuster
In clinical trials, a placebo response refers to improvement in disease symptoms arising from the psychological effect of receiving a treatment rather than the actual treatment under investigation. Previous research has reported genomic variation associated with the likelihood of observing a placebo response, but these studies have been limited in scope and have not been validated. Here, we analyzed whole-genome sequencing data from 784 patients undergoing placebo treatment in Phase III Asthma or Rheumatoid Arthritis trials to assess the impact of previously reported variation on patient outcomes in the placebo arms and to identify novel variants associated with the placebo response...
March 18, 2018: Genes and Immunity
Sophia David, Massimo Mentasti, Julian Parkhill, Victoria J Chalker
OBJECTIVES: Legionella pneumophila is the leading cause of Legionnaires' disease, a severe form of pneumonia acquired from environmental sources. Investigations of both sporadic cases and outbreaks mostly rely on analysis of a single to a few colony pick(s) isolated from each patient. However, due to the lack of data describing diversity within single patients, the optimal number of picks is unknown. Here, we investigated diversity within individual patients using sequence based typing (SBT) and whole genome sequencing (WGS)...
March 13, 2018: Clinical Microbiology and Infection
Marco van Zwetselaar, Balthazar Nyombi, Tolbert Sonda, Happiness Kumburu, Nyasatu Chamba, Marieke C J Dekker, Kajiru G Kilonzo, Sarah J Urasa, Blandina T Mmbaga
BACKGROUND: Aeromonas species have been documented to yield false positive results in microbiological tests for Vibrio cholerae. They share many biochemical properties with Vibrio species, with which they were jointly classified in the family Vibrionaceae until genotypic information provided new insights. Aeromonas species are increasingly associated with gastrointestinal infections, albeit with great apparent variation in pathogenicity and virulence both between and within species of the genus...
March 17, 2018: Journal of Medical Case Reports
Xiangfeng Wang, Hu Fang, Yong Cheng, Lin Li, Xiaohui Sun, Tao Fu, Peide Huang, Anping Zhang, Zhimin Feng, Chunxue Li, Xuanlin Huang, Guangyan Li, Peina Du, Huanming Yang, Xiaodong Fang, Fan Li, Qiang Gao, Baohua Liu
Synchronous colorectal cancers (syCRCs), which present two or more lesions at diagnosis, are rare and pose a great challenge for clinical management. Although some predisposing factors associated with syCRCs have been studied with limited accession, the full repertoire of genomic events among the lesions within an individual and the causes of syCRCs remain unclear. We performed whole-exome sequencing of 40 surgical tumour samples of paired lesions from 20 patients to characterize the genetic alterations. Lesions from same patient showed distinct landscapes of somatic aberrations and shared few mutations, which suggests that they originate and develop independently although they shared the similar genetic background...
March 13, 2018: Carcinogenesis
Pragathi B Shridhar, Isha R Patel, Jayanthi Gangiredla, Lance W Noll, Xiaorong Shi, Jianfa Bai, Christopher A Elkins, Nancy A Strockbine, T G Nagaraja
Escherichia coli O104:H4, a Shiga toxin-producing hybrid pathotype that was implicated in a major foodborne outbreak in Germany in 2011, has not been detected in cattle. However, serotypes of O104, other than O104:H4, have been isolated from cattle feces, with O104:H7 being the most predominant. In this study, we investigated, based on whole genome sequence analyses, the virulence potential of E. coli O104 strains isolated from cattle feces, since cattle are asymptomatic carriers of E. coli O104. The genomes of ten bovine E...
2018: Frontiers in Microbiology
Ramani Baddam, Narender Kumar, Lothar H Wieler, Aditya Kumar Lankapalli, Niyaz Ahmed, Sharon J Peacock, Torsten Semmler
Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug, resistance to which occurs primarily due to mutations in pncA (Rv2043c) that encodes the pyrazinamidase enzyme responsible for conversion of pro-drug PZA into its active form. Previous studies have reported numerous resistance-conferring mutations distributed across the entire length of pncA without any hotspot regions. As different lineages of Mycobacterium tuberculosis display a strong geographic association, we sought to understand whether the genetic background influenced the distribution of mutations in pncA...
March 15, 2018: Scientific Reports
Zornitza Stark, Sebastian Lunke, Gemma R Brett, Natalie B Tan, Rachel Stapleton, Smitha Kumble, Alison Yeung, Dean G Phelan, Belinda Chong, Miriam Fanjul-Fernandez, Justine E Marum, Matthew Hunter, Anna Jarmolowicz, Yael Prawer, Jessica R Riseley, Matthew Regan, Justine Elliott, Melissa Martyn, Stephanie Best, Tiong Y Tan, Clara L Gaff, Susan M White
PurposeThe purpose of the study was to implement and prospectively evaluate the outcomes of a rapid genomic diagnosis program at two pediatric tertiary centers.MethodsRapid singleton whole-exome sequencing (rWES) was performed in acutely unwell pediatric patients with suspected monogenic disorders. Laboratory and clinical barriers to implementation were addressed through continuous multidisciplinary review of process parameters. Diagnostic and clinical utility and cost-effectiveness of rWES were assessed.ResultsOf 40 enrolled patients, 21 (52...
March 15, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Yan Hao, Dawei Chen, Zhiguo Zhang, Ping Zhou, Yunxia Cao, Zhaolian Wei, Xiaofeng Xu, Beili Chen, Weiwei Zou, Mingrong Lv, Dongmei Ji, Xiaojin He
Hearing loss may place a heavy burden on the patient and patient's family. Given the high incidence of hearing loss among newborns and the huge cost of treatment and care (including cochlear implantation), prenatal diagnosis is strongly recommended. Termination of the fetus may be considered as an extreme outcome to the discovery of a potential deaf fetus, and therefore preimplantation genetic diagnosis has become an important option for avoiding the birth of affected children without facing the risk of abortion following prenatal diagnosis...
April 2018: Oncology Letters
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"