scholarly journals Identification of Structural Variation from NGS-Based Non-Invasive Prenatal Testing

2019 ◽  
Vol 20 (18) ◽  
pp. 4403 ◽  
Author(s):  
Ondrej Pös ◽  
Jaroslav Budis ◽  
Zuzana Kubiritova ◽  
Marcel Kucharik ◽  
Frantisek Duris ◽  
...  
Keyword(s):  
Genetic Diseases ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
Genomic Data ◽  
Population Diversity ◽  
Clinical Diagnostics ◽  
Plasma Dna ◽  
Non Invasive ◽  
Slovak Population ◽  
Pathogenic Variants

Copy number variants (CNVs) are an important type of human genome variation, which play a significant role in evolution contribute to population diversity and human genetic diseases. In recent years, next generation sequencing has become a valuable tool for clinical diagnostics and to provide sensitive and accurate approaches for detecting CNVs. In our previous work, we described a non-invasive prenatal test (NIPT) based on low-coverage massively parallel whole-genome sequencing of total plasma DNA for detection of CNV aberrations ≥600 kbp. We reanalyzed NIPT genomic data from 5018 patients to evaluate CNV aberrations in the Slovak population. Our analysis of autosomal chromosomes identified 225 maternal CNVs (47 deletions; 178 duplications) ranging from 600 to 7820 kbp. According to the ClinVar database, 137 CNVs (60.89%) were fully overlapping with previously annotated variants, 66 CNVs (29.33%) were in partial overlap, and 22 CNVs (9.78%) did not overlap with any previously described variant. Identified variants were further classified with the AnnotSV method. In summary, we identified 129 likely benign variants, 13 variants of uncertain significance, and 83 likely pathogenic variants. In this study, we use NIPT as a valuable source of population specific data. Our results suggest the utility of genomic data from commercial CNV analysis test as background for a population study.

scholarly journals Repurposing Non-invasive prenatal testing data; population study of single nucleotide variants associated with colorectal cancer and Lynch syndrome

2021 ◽  
Author(s):  
Natalia Forgacova ◽  
Juraj Gazdarica ◽  
Jaroslav Budis ◽  
Jan Radvanszky ◽  
Tomas Szemes
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Prenatal Testing ◽  
Allelic Frequency ◽  
Plasma Dna ◽  
Single Nucleotide Variants ◽  
Non Invasive ◽  
Slovak Population ◽  
Pathogenic Variants ◽  
Risk Variants

Abstract PURPOSE: In our previous work, we described genomic data generated through non-invasive prenatal testing (NIPT) based on low-coverage massively parallel whole-genome sequencing of total plasma DNA of pregnant women in Slovakia as a valuable source of population specific data. In the present study, we used these data to determine the population allele frequency of common risk variants located in genes associated with colorectal cancer (CRC) and Lynch syndrome (LS). METHODS: Allele frequencies of identified variants were compared with six world populations to detect significant differences between populations. Finally, we interpreted variants and searched for functional consequences and clinical significance of variants using publicly available databases.RESULTS: Although we could not identify any pathogenic variants associated with CRC or LS in the Slovak population using NIPT data, we observed significant differences in the allelic frequency of risk CRC variants previously reported in GWAS and common variants located in genes associated with LS. CONCLUSION: As Slovakia is the third country with the highest incidence of CRC per 100 000 population in the world, we highlight a need for studies dedicated to the cause of such a high incidence of CRC in Slovakia. We also assume that extensive cross-country data aggregation of NIPT results would represent an unprecedented source of information about human genome variation, also in cancer research.

scholarly journals Detection of fetal copy number variants by non-invasive prenatal testing for common aneuploidies

2016 ◽  
Vol 47 (1) ◽  
pp. 53-57 ◽  
Author(s):  
R. Li ◽  
J. Wan ◽  
Y. Zhang ◽  
F. Fu ◽  
Y. Ou ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Prenatal Testing ◽  
Non Invasive

Cell-free DNA and RNA - measurement and applications in clinical diagnostics with focus on metabolic disorders

2020 ◽  
Author(s):  
Markus Hodal Drag ◽  
Tuomas Oskari Kilpeläinen
Keyword(s):  
Metabolic Disorders ◽  
Solid Organ Transplantation ◽  
Prenatal Testing ◽  
Clinical Diagnostics ◽  
Solid Organ ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Free Dna

Circulating cell-free DNA (cfDNA) and RNA (cfRNA) hold enormous potential as a new class of biomarkers for the development of non-invasive liquid biopsies in many diseases and conditions. In recent years, cfDNA and cfRNA have been studied intensely as tools for non-invasive prenatal testing, solid organ transplantation, cancer screening, and monitoring of tumors. In obesity, higher cfDNA concentration indicates accelerated cellular turnover of adipocytes during expansion of adipose mass and may be directly involved in the development of adipose tissue insulin resistance by inducing inflammation. Furthermore, cfDNA and cfRNA have promising diagnostic value in a range of obesity-related metabolic disorders, such as non-alcoholic fatty liver disease, type 2 diabetes, and diabetic complications. Here, we review the current and future applications of cfDNA and cfRNA within clinical diagnostics, discuss technical and analytical challenges in the field, and summarise the opportunities of using cfDNA and cfRNA in the diagnostics and prognostics of obesity-related metabolic disorders.

scholarly journals Copy Number Variation: Methods and Clinical Applications

2021 ◽  
Vol 11 (2) ◽  
pp. 819
Author(s):  
Ondrej Pös ◽  
Jan Radvanszky ◽  
Jakub Styk ◽  
Zuzana Pös ◽  
Gergely Buglyó ◽  
...  
Keyword(s):  
Copy Number ◽  
Genetic Diseases ◽  
Copy Number Variants ◽  
Clinical Diagnostics ◽  
Whole Body ◽  
Current State ◽  
Number Variation ◽  
Detection Capabilities ◽  
Gains And Losses ◽  
Cnv Detection

Gains and losses of large segments of genomic DNA, known as copy number variants (CNVs) gained considerable interest in clinical diagnostics lately, as particular forms may lead to inherited genetic diseases. In recent decades, researchers developed a wide variety of cytogenetic and molecular methods with different detection capabilities to detect clinically relevant CNVs. In this review, we summarize methodological progress from conventional approaches to current state of the art techniques capable of detecting CNVs from a few bases up to several megabases. Although the recent rapid progress of sequencing methods has enabled precise detection of CNVs, determining their functional effect on cellular and whole-body physiology remains a challenge. Here, we provide a comprehensive list of databases and bioinformatics tools that may serve as useful assets for researchers, laboratory diagnosticians, and clinical geneticists facing the challenge of CNV detection and interpretation.

scholarly journals SUN-721 Implementation of Whole Exome Sequencing for Clinical Diagnostics: A Prospective Busan Kyung-Sang Regional Co-Work Team Experience

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jeong Eun Lee ◽  
WooYeong Chung ◽  
BoLyun Lee ◽  
SooHyun Ku ◽  
Ga Won Jeon ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Diagnostic Yield ◽  
Genetic Disorder ◽  
Genetic Diseases ◽  
Clinical Diagnostics ◽  
Buccal Swab ◽  
Variant Interpretation ◽  
Pathogenic Variants ◽  
Whole Exome

Abstract Purpose: Next Generation Sequencing (NGS) technology is a highthroughput method for genome sequencing which assists clinicians with diagnosis of patients with suspected genetic disorders. This study was to investigate diagnostic yield and clinical utility of whole exome sequencing prospectively in the rare genetic diseases. Method: WES was performed a total of 178 patients with suspected genetic disorder. Buccal swab samples were collected from the patients to extract genomic DNA. WES and variant interpretation was conducted in 3 Billion Inc (Seoul, Republic of Korea), based on their own software. Patients’ phenotype was interpreted by clinical geneticists. Results: WES reported 117 variants (66.7%). According to the ACMG/AMP guidelines, there were 25 pathogenic variants (14%), 37 likely pathogenic variants (32%), and 55 VUS (31%). Among the 117 patients who detected variants, genotype-phenotype correlation was analyzed and resulted that 44 (38%) were found to be apparently causal mutation of the disease, 37 (32%) were not considered the cause of the disease, and 36 (31%) were withheld judgement. Of the VUS variants, 13% were likely to be the causal variants of the disease considering phenotype of patients. Conclusion: This study showed 38% of diagnostic yield in patients with unidentified genetic condition by using prospective WES based on automating variant interpretation system. In the diagnosis of rare genetic disease, we identified the need for a multi-disciplinary team to select appropriate subjects and interpret the clinical significance of the found genetic variants.

Sign in / Sign up

Export Citation Format

Share Document