Whole Exome Sequencing

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Masanobu Yamada - One of the best experts on this subject based on the ideXlab platform.

  • Whole-Exome Sequencing Study of Thyrotropin-Secreting Pituitary Adenomas
    The Journal of clinical endocrinology and metabolism, 2016
    Co-Authors: Santosh Sapkota, Kazuhiko Horiguchi, Masahiko Tosaka, Syozo Yamada, Masanobu Yamada
    Abstract:

    Context:Thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism, and the genetic aberrations responsible remain unknown.Objective:To identify somatic genetic abnormalities in TSHomas.Designand Setting: A single-nucleotide polymorphism (SNP) array analysis was performed on 8 TSHomas. Four tumors with no allelic losses or limited loss-of-heterozygosity were selected and Whole-Exome Sequencing was performed including their corresponding blood samples. Somatic variants were confirmed by Sanger Sequencing. A set of 8 tumors was also assessed to validate candidate genes.Patients:Twelve patients with sporadic TSHomas were examined.Intervention:No intervention was performed.Results:The overall performance of Whole-Exome Sequencing was good, with an average coverage of each base in the targeted region of 97.6%. Six novel DNA variants were confirmed as candidate driver mutations, with an average of 1.5 somatic mutations per tumor. No mutations were recurrent. Two of these mutati...

Stephanie M Ware - One of the best experts on this subject based on the ideXlab platform.

  • SHROOM3 is a novel candidate for heterotaxy identified by Whole Exome Sequencing
    Genome Biology, 2011
    Co-Authors: Muhammad Tariq, John W Belmont, Seema Lalani, Teresa Smolarek, Stephanie M Ware
    Abstract:

    Background Heterotaxy-spectrum cardiovascular disorders are challenging for traditional genetic analyses because of clinical and genetic heterogeneity, variable expressivity, and non-penetrance. In this study, high-resolution SNP genotyping and exon-targeted array comparative genomic hybridization platforms were coupled to Whole-Exome Sequencing to identify a novel disease candidate gene. Results SNP genotyping identified absence-of-heterozygosity regions in the heterotaxy proband on chromosomes 1, 4, 7, 13, 15, 18, consistent with parental consanguinity. Subsequently, Whole-Exome Sequencing of the proband identified 26,065 coding variants, including 18 non-synonymous homozygous changes not present in dbSNP132 or 1000 Genomes. Of these 18, only 4 - one each in CXCL2 , SHROOM3 , CTSO , RXFP1 - were mapped to the absence-of-heterozygosity regions, each of which was flanked by more than 50 homozygous SNPs, confirming recessive segregation of mutant alleles. Sanger Sequencing confirmed the SHROOM3 homozygous missense mutation and it was predicted as pathogenic by four bioinformatic tools. SHROOM3 has been identified as a central regulator of morphogenetic cell shape changes necessary for organogenesis and can physically bind ROCK2, a rho kinase protein required for left-right patterning. Screening 96 sporadic heterotaxy patients identified four additional patients with rare variants in SHROOM3 . Conclusions Using Whole Exome Sequencing, we identify a recessive missense mutation in SHROOM3 associated with heterotaxy syndrome and identify rare variants in subsequent screening of a heterotaxy cohort, suggesting SHROOM3 as a novel target for the control of left-right patterning. This study reveals the value of SNP genotyping coupled with high-throughput Sequencing for identification of high yield candidates for rare disorders with genetic and phenotypic heterogeneity.

  • SHROOM3 is a novel candidate for heterotaxy identified by Whole Exome Sequencing
    Genome biology, 2011
    Co-Authors: Muhammad Tariq, John W Belmont, Teresa Smolarek, Seema R. Lalani, Stephanie M Ware
    Abstract:

    Background Heterotaxy-spectrum cardiovascular disorders are challenging for traditional genetic analyses because of clinical and genetic heterogeneity, variable expressivity, and non-penetrance. In this study, high-resolution SNP genotyping and exon-targeted array comparative genomic hybridization platforms were coupled to Whole-Exome Sequencing to identify a novel disease candidate gene.

Eng-king Tan - One of the best experts on this subject based on the ideXlab platform.

  • Whole-genome and Whole-Exome Sequencing in neurological diseases
    Nature Reviews Neurology, 2012
    Co-Authors: Jia-nee Foo, Jian-jun Liu, Eng-king Tan
    Abstract:

    Whole-genome and Whole-Exome Sequencing is becoming increasingly affordable for use in a clinical setting Recent studies demonstrate successes in applying Whole-genome or Whole-Exome Sequencing to disease gene discovery and clinical diagnosis of complex neurological diseases, but they also highlight major challenges in data interpretation The various tools and methods that have been developed to process next-generation Sequencing data and to parse the list of genomic variants must be carefully evaluated for clinical use The majority of genomic variants do not have known or confirmed clinical effects, and caution is needed in the interpretation and reporting of genetic results Basic guidelines have been drawn up for the implementation of genetic testing in a clinical setting; these guidelines are likely to be reviewed and changed over time Next-generation Sequencing approaches are becoming increasingly affordable for use in the clinical setting, and have the potential to provide valuable insights into the genetic underpinnings of complex neurological diseases. In this Review, Foo et al . discuss how Whole-genome and Whole-Exome Sequencing data can be deciphered, and consider how such data might be used for diagnosis and risk prediction in the neurology clinic. Genetic risk factors that underlie many rare and common neurological disorders remain poorly understood because of the multifactorial and heterogeneous nature of these complex traits. With the decreasing cost of massively parallel Sequencing technologies, Whole-genome and Whole-Exome Sequencing will soon allow the characterization of the full spectrum of sequence and structural variants present in each individual. Methods are being developed to parse the huge amount of genomic data and to sift out which variants are associated with diseases. Numerous challenges are inherent in the identification of rare and common variants that have a role in complex neurological diseases, and tools are being developed to overcome these challenges. Given that genomic data will soon be the main driver towards the goal of personalized medicine, future developments in the production and interpretation of data, as well as in ethics and counselling, will be needed for Whole-genome and Whole-Exome Sequencing to be used as informative tools in a clinical setting.

  • Whole-genome and Whole-Exome Sequencing in neurological diseases
    Nature reviews. Neurology, 2012
    Co-Authors: Jia-nee Foo, Jian-jun Liu, Eng-king Tan
    Abstract:

    Genetic risk factors that underlie many rare and common neurological disorders remain poorly understood because of the multifactorial and heterogeneous nature of these complex traits. With the decreasing cost of massively parallel Sequencing technologies, Whole-genome and Whole-Exome Sequencing will soon allow the characterization of the full spectrum of sequence and structural variants present in each individual. Methods are being developed to parse the huge amount of genomic data and to sift out which variants are associated with diseases. Numerous challenges are inherent in the identification of rare and common variants that have a role in complex neurological diseases, and tools are being developed to overcome these challenges. Given that genomic data will soon be the main driver towards the goal of personalized medicine, future developments in the production and interpretation of data, as well as in ethics and counselling, will be needed for Whole-genome and Whole-Exome Sequencing to be used as informative tools in a clinical setting.

Danya F. Vears - One of the best experts on this subject based on the ideXlab platform.

Chanjuan Hao - One of the best experts on this subject based on the ideXlab platform.

  • Parallel Tests of Whole Exome Sequencing and Copy Number Variant Sequencing Increase the Diagnosis Yields of Rare Pediatric Disorders.
    Frontiers in genetics, 2020
    Co-Authors: Ruolan Guo, Jun Guo, Chanjuan Hao
    Abstract:

    Background: Both Whole Exome Sequencing and copy number variants Sequencing were applied to identify the genetic cause of rare pediatric disorders. In our study, we aimed to investigate the diagnostic yield of parallel tests of trio Whole Exome Sequencing and copy number variants Sequencing and its clinical utility. Methods: After collecting detailed clinical information, a total of 60 patients were referred to parallel tests of Whole Exome Sequencing and copy number variants Sequencing, which used shared initial libraries. Results: 26 pathogenic or likely pathogenic single nucleotide variants and 11 copy number variants were identified in 32 patients. 65.4% (17/26) of the SNVs were novel. The overall diagnosis rate was 53.3%. For the patients with positive results, 22 (36.7%) patients were diagnosed by Whole Exome Sequencing and 10 (16.7%) patients were diagnosed by copy number variants Sequencing. We also reviewed clinical impact on selected cases. Conclusion: We adopted an approach by performing parallel tests of trio Whole Exome Sequencing and copy number variants Sequencing with shared initial libraries. This strategy is relatively efficient and cost-effective for the diagnosis of rare pediatric disorders with high heterogeneity.