scholarly journals Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next‐generation sequencing

2020 ◽  
Vol 182 (8) ◽  
pp. 1906-1912 ◽  
Author(s):  
Johanna L. Schmidt ◽  
Amy Pizzino ◽  
Jessica Nicholl ◽  
Allison Foley ◽  
Yue Wang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Relative Frequency ◽  
Carrier Screening ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Carrier screening by next‐generation sequencing: health benefits and cost effectiveness

2016 ◽  
Vol 4 (3) ◽  
pp. 292-302 ◽  
Author(s):  
Mohammad Azimi ◽  
Kyle Schmaus ◽  
Valerie Greger ◽  
Dana Neitzel ◽  
Robert Rochelle ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Next Generation Sequencing ◽  
Health Benefits ◽  
Carrier Screening ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Combined use of gap-PCR and next-generation sequencing improves thalassaemia carrier screening among premarital adults in China

2020 ◽  
Vol 73 (8) ◽  
pp. 488-492 ◽  
Author(s):  
Jianghong Zhao ◽  
Jia Li ◽  
Qiaohong Lai ◽  
Yanping Yu
Keyword(s):  
Next Generation Sequencing ◽  
Southern China ◽  
Cost Effective ◽  
Carrier Screening ◽  
Lower Sensitivity ◽  
Carrier Rate ◽  
Next Generation ◽  
Cost Effective Method ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

AimsThalassaemia is one of the most common genetics disorders in the world, especially in southern China. The aim of the present study was to investigate the feasibility of combining the gap-PCR and next-generation sequencing (NGS) for thalassaemia carrier screening in the Chinese population.MethodsBlood samples were obtained from 944 prepregnancy couples; thalassaemia carrier screening was performed by using a routine haematological method and a combination of gap-PCR and NGS method.ResultsWe found that the α thalassaemia carrier rate was 11% (207/1888); the β thalassaemia carrier rate was 3.7% (70/1888); the composite α thalassaemia and β thalassaemia carrier rate was 0.4% (8/1888). We also identified seven novel mutations, including HBA1: c.412A>G, −50 (G>A), HBB: c.*+129T>A, HBB: c.-64G>C, HBB: c.-180G>C, HBB: c.*+5G>A and HBB: c.-113A>G. By comparing the combined gap-PCR and NGS method, the MCV+MCH and HbA2 detection strategy showed a lower sensitivity of 61.05% (105/172) and a higher missed diagnosis ratio of 38.95% (67/172) for α thalassaemia mutations. The sensitivity was improved with the MCV+MCH and HbA2 detection screen when compared with MCV+MCH detection for β thalassaemia (98.51% vs 85.90%).ConclusionsOur study suggests the combined gap-PCR and NGS method is a cost-effective method for the thalassaemia carrier screening, particularly for the α thalassaemia mutation carriers.

Preconception genome medicine: current state and future perspectives to improve infertility diagnosis and reproductive and health outcomes based on individual genomic data

2020 ◽  
Author(s):  
Antonio Capalbo ◽  
Maurizio Poli ◽  
Antoni Riera-Escamilla ◽  
Vallari Shukla ◽  
Miya Kudo Høffding ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Association Studies ◽  
Carrier Screening ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Next Generation ◽  
Secondary Findings ◽  
Pubmed Central ◽  
Genome Wide ◽  
Generation Sequencing

Abstract BACKGROUND Our genetic code is now readable, writable and hackable. The recent escalation of genome-wide sequencing (GS) applications in population diagnostics will not only enable the assessment of risks of transmitting well-defined monogenic disorders at preconceptional stages (i.e. carrier screening), but also facilitate identification of multifactorial genetic predispositions to sub-lethal pathologies, including those affecting reproductive fitness. Through GS, the acquisition and curation of reproductive-related findings will warrant the expansion of genetic assessment to new areas of genomic prediction of reproductive phenotypes, pharmacogenomics and molecular embryology, further boosting our knowledge and therapeutic tools for treating infertility and improving women’s health. OBJECTIVE AND RATIONALE In this article, we review current knowledge and potential development of preconception genome analysis aimed at detecting reproductive and individual health risks (recessive genetic disease and medically actionable secondary findings) as well as anticipating specific reproductive outcomes, particularly in the context of IVF. The extension of reproductive genetic risk assessment to the general population and IVF couples will lead to the identification of couples who carry recessive mutations, as well as sub-lethal conditions prior to conception. This approach will provide increased reproductive autonomy to couples, particularly in those cases where preimplantation genetic testing is an available option to avoid the transmission of undesirable conditions. In addition, GS on prospective infertility patients will enable genome-wide association studies specific for infertility phenotypes such as predisposition to premature ovarian failure, increased risk of aneuploidies, complete oocyte immaturity or blastocyst development failure, thus empowering the development of true reproductive precision medicine. SEARCH METHODS Searches of the literature on PubMed Central included combinations of the following MeSH terms: human, genetics, genomics, variants, male, female, fertility, next generation sequencing, genome exome sequencing, expanded carrier screening, secondary findings, pharmacogenomics, controlled ovarian stimulation, preconception, genetics, genome-wide association studies, GWAS. OUTCOMES Through PubMed Central queries, we identified a total of 1409 articles. The full list of articles was assessed for date of publication, limiting the search to studies published within the last 15 years (2004 onwards due to escalating research output of next-generation sequencing studies from that date). The remaining articles’ titles were assessed for pertinence to the topic, leaving a total of 644 articles. The use of preconception GS has the potential to identify inheritable genetic conditions concealed in the genome of around 4% of couples looking to conceive. Genomic information during reproductive age will also be useful to anticipate late-onset medically actionable conditions with strong genetic background in around 2–4% of all individuals. Genetic variants correlated with differential response to pharmaceutical treatment in IVF, and clear genotype–phenotype associations are found for aberrant sperm types, oocyte maturation, fertilization or pre- and post-implantation embryonic development. All currently known capabilities of GS at the preconception stage are reviewed along with persisting and forthcoming barriers for the implementation of precise reproductive medicine. WIDER IMPLICATIONS The expansion of sequencing analysis to additional monogenic and polygenic traits may enable the development of cost-effective preconception tests capable of identifying underlying genetic causes of infertility, which have been defined as ‘unexplained’ until now, thus leading to the development of a true personalized genomic medicine framework in reproductive health.

Clinical diagnostic Next-Generation sequencing: The case of CFTR carrier screening

2015 ◽  
Vol 75 (5) ◽  
pp. 374-381 ◽  
Author(s):  
Yannis L. Loukas ◽  
Georgia Thodi ◽  
Elina Molou ◽  
Vassiliki Georgiou ◽  
Yannis Dotsikas ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Carrier Screening ◽  
Next Generation ◽  
Clinical Diagnostic ◽  
Generation Sequencing

scholarly journals NGS4THAL, a one-stop molecular diagnosis and carrier screening tool for thalassemia and other hemoglobinopathies by next-generation sequencing

2021 ◽  
Author(s):  
Yujie Cao ◽  
Shau Yin Ha ◽  
Chi-Chiu So ◽  
Tong Ming For ◽  
Clara Sze-Man Tang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Diagnosis ◽  
Carrier Screening ◽  
Detection Accuracy ◽  
Next Generation ◽  
Sequencing Data ◽  
Pathogenic Variants ◽  
Accurate Detection ◽  
Ngs Data ◽  
Generation Sequencing

Abstract Background Thalassemia is one of the most common genetic diseases and a major health threat worldwide. Accurate, efficient and scalable genetic testing methodology is much needed for its molecular diagnosis and carrier screening.Results We developed NGS4THAL, a bioinformatics analysis pipeline analyzing next generation sequencing (NGS) data to detect pathogenic variants for thalassemia and other hemoglobinopathies. NGS4THAL recovers and realigns ambiguously mapped NGS reads derived from the homologous hemoglobin gene clusters to achieve accurate detection of point mutations and small insertion/deletions (InDels). And it uses several structural variant (SV) detection tools with complementary algorithms, and an inhouse database with control data on a number of known SVs to achieve accurate detection of hemoglobin SVs. Detected variants are matched with those in HbVar, allowing recognition of known pathogenic variants, including disease modifiers. Tested on simulation data, NGS4THAL achieved high sensitivity and specificity. For targeted NGS sequencing data from samples with laboratory-confirmed pathogenic hemoglobin variants, it achieved 100% detection accuracy. Application of NGS4THAL on whole genome sequencing data from unrelated studies detected thalassemia mutation carrier rates for Hong Kong Chinese and Northern Vietnamese that were consistent with those from epidemiological studies.Conclusions NGS4THAL is a highly accurate and efficient molecular diagnosis tool for thalassemia and other hemoglobinopathies based on tailored analysis of NGS data, and is potentially scalable for carrier screening purposes.

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