scholarly journals Identification of a novel heterozygous SPTB mutation by whole genome sequencing in a Chinese patient with hereditary spherocytosis and atrial septal defect: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhanhui Du ◽  
Gang Luo ◽  
Kuiliang Wang ◽  
Zhen Bing ◽  
Silin Pan
Keyword(s):  
Atrial Septal Defect ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Chinese Population ◽  
Septal Defect ◽  
Hereditary Spherocytosis ◽  
Valuable Insight ◽  
Whole Genome ◽  
Biochemical Tests ◽  
Chinese Girl

Abstract Background Hereditary spherocytosis (HS) is a common inherited red blood cell membrane disorder characterized by an abnormal increase of spherocytes in peripheral blood. SPTB gene mutation is one of the most common causes of HS; however, few cases of HS resulting from SPTB mutation in the Chinese population have been reported so far. Case presentation A 3-year-old Chinese girl presented to Qingdao Women and Children’s Hospital, Qingdao University, with atrial septal defect (ASD). Meanwhile, she was clinically diagnosed with HS. Whole genome sequencing (WGS) was performed for the proband and her parents for genetic molecular analysis. A novel SPTB mutation (c.1756delG) was detected by WGS and confirmed by Sanger sequencing in the proband. This mutation results in a frameshift with a premature termination codon in exon 12, leading to a nonsense mutation (p.Ala586Profs*7). Her parents had no similar symptoms, and blood routine and serum biochemical tests showed no significant abnormalities. The patient’s mother did not know of any relatives with HS-like symptoms. Percutaneous transcatheter closure was successfully performed for treating the ASD. Conclusion In this study, we identified a novel SPTB frameshift mutation in a Chinese girl with HS. This finding would expand the spectrum of SPTB mutations, provide a valuable insight into the genotyping of HS in the Chinese population, and contribute to the clinical management and genetic counseling in HS.

scholarly journals NyuWa Genome Resource: Deep Whole Genome Sequencing Based Chinese Population Variation Profile and Reference Panel

2020 ◽  
Author(s):  
Peng Zhang ◽  
Huaxia Luo ◽  
Yanyan Li ◽  
You Wang ◽  
Jiajia Wang ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Chinese Population ◽  
Population Variation ◽  
Reference Panel ◽  
Specific Reference ◽  
Whole Genome ◽  
Loss Of Function ◽  
Southern Chinese ◽  
Novel Variants

AbstractThe lack of Chinese population specific haplotype reference panel and whole genome sequencing resources has greatly hindered the genetics studies in the world’s largest population. Here we presented the NyuWa genome resource of 71.1M SNPs and 8.2M indels based on deep (26.2X) sequencing of 2,999 Chinese individuals, and constructed NyuWa reference panel of 5,804 haplotypes and 19.3M variants, which is the first publicly available Chinese population specific reference panel with thousands of samples. There were 25.0M novel variants in NyuWa genome resource, and 3.2M specific variants in NyuWa reference panel. Compared with other panels, NyuWa reference panel reduces the Han Chinese imputation error rate by the range of 30% to 51%. Population structure and imputation simulation tests supported the applicability of one integrated reference panel for both northern and southern Chinese. In addition, a total of 22,504 loss-of-function variants in coding and noncoding genes were identified, including 11,493 novel variants. These results highlight the value of NyuWa genome resource to facilitate genetics research in Chinese and Asian populations.

scholarly journals NyuWa Genome resource: A deep whole-genome sequencing-based variation profile and reference panel for the Chinese population

Cell Reports ◽  
2021 ◽  
Vol 37 (7) ◽  
pp. 110017
Author(s):  
Peng Zhang ◽  
Huaxia Luo ◽  
Yanyan Li ◽  
You Wang ◽  
Jiajia Wang ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Chinese Population ◽  
Reference Panel ◽  
Whole Genome

scholarly journals CTX-M-15-Producing Shewanella Species Clinical Isolate Expressing OXA-535, a Chromosome-Encoded OXA-48 Variant, Putative Progenitor of the Plasmid-Encoded OXA-436

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Agnès B. Jousset ◽  
Laura Dabos ◽  
Rémy A. Bonnin ◽  
Delphine Girlich ◽  
Anaïs Potron ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Clinical Isolate ◽  
Genome Sequencing ◽  
Bacterial Species ◽  
Whole Genome ◽  
Biochemical Tests ◽  
Bile Sample ◽  
Content Type ◽  
E Coli ◽  
Shewanella Species

ABSTRACT Shewanella spp. constitute a reservoir of antibiotic resistance determinants. In a bile sample, we identified three extended-spectrum-β-lactamase (ESBL)-producing bacteria (Escherichia coli, Klebsiella pneumoniae, and Shewanella sp. strain JAB-1) isolated from a child suffering from cholangitis. Our objectives were to characterize the genome and the resistome of the first ESBL-producing isolate of the genus Shewanella and determine whether plasmidic exchange occurred between the three bacterial species. Bacterial isolates were characterized using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), standard biochemical tools, and antimicrobial susceptibility testing. Shewanella sp. JAB-1 and ESBL gene-encoding plasmids were characterized using PacBio and Illumina whole-genome sequencing, respectively. The Shewanella sp. JAB-1 chromosome-encoded OXA-48 variant was cloned and functionally characterized. Whole-genome sequencing (WGS) of the Shewanella sp. clinical isolate JAB-1 revealed the presence of a 193-kb plasmid belonging to the IncA/C incompatibility group and harboring two ESBL genes, bla CTX-M-15 and bla SHV-2a. bla CTX-M-15 gene-carrying plasmids belonging to the IncY and IncR incompatibility groups were also found in the E. coli and K. pneumoniae isolates from the same patient, respectively. A comparison of the bla CTX-M-15 genetic environment indicated the independent origin of these plasmids and dismissed in vivo transfers. Furthermore, characterization of the resistome of Shewanella sp. JAB-1 revealed the presence of a chromosome-carried bla OXA-535 gene, likely the progenitor of the plasmid-carried bla OXA-436 gene, a novel bla OXA-48-like gene. The expression of bla OXA-535 in E. coli showed the carbapenem-hydrolyzing activity of OXA-535. The production of OXA-535 in Shewanella sp. JAB-1 could be evidenced using molecular and immunoenzymatic tests, but not with biochemical tests that monitor carbapenem hydrolysis. In this study, we have identified a CTX-M-15-producing Shewanella species that was responsible for a hepatobiliary infection and that is likely the progenitor of OXA-436, a novel plasmid-encoded OXA-48-like class D carbapenemase.

scholarly journals Proficiency Testing for bacterial whole genome sequencing in assuring the quality of microbiology diagnostics in clinical and public health laboratories

2020 ◽  
Author(s):  
Katherine A. Lau ◽  
Anders Gonçalves da Silva ◽  
Torsten Theis ◽  
Joanna Gray ◽  
Susan A Ballard ◽  
...  
Keyword(s):  
Public Health ◽  
Whole Genome Sequencing ◽  
Proficiency Testing ◽  
Genome Sequencing ◽  
Clinical Microbiology ◽  
Quality Data ◽  
Valuable Insight ◽  
Whole Genome ◽  
Diverse Range ◽  
Minimum Requirements

ABSTRACTThe adoption of whole genome sequencing (WGS) data over the past decade for pathogen surveillance, and decision-making for infectious diseases has rapidly transformed the landscape of clinical microbiology and public health. However, for successful transition to routine use of these techniques, it is crucial to ensure the WGS data generated meet defined quality standards for pathogen identification, typing, antimicrobial resistance detection and surveillance. Further, the ongoing development of these standards will ensure that the bioinformatic processes are capable of accurately identifying and characterising organisms of interest, and thereby facilitate the integration of WGS into routine clinical and public health laboratory setting. A pilot proficiency testing (PT) program for WGS of infectious agents was developed to facilitate widely applicable standardisation and benchmarking standards for WGS across a range of laboratories. The PT participating laboratories were required to generate WGS data from two bacterial isolates, and submit the raw data for independent bioinformatics analysis, as well as analyse the data with their own processes and answer relevant questions about the data. Overall, laboratories used a diverse range of bioinformatics tools and could generate and analyse high-quality data, either meeting or exceeding the minimum requirements. This pilot has provided valuable insight into the current state of genomics in clinical microbiology and public health laboratories across Australia. It will provide a baseline guide for the standardisation of WGS and enable the development of a PT program that allows an ongoing performance benchmark for accreditation of WGS-based test processes.

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