scholarly journals A whole-genome sequencing–based novel preimplantation genetic testing method for de novo mutations combined with chromosomal balanced translocations

2020 ◽  
Vol 37 (10) ◽  
pp. 2525-2533
Author(s):  
Ping Yuan ◽  
Jun Xia ◽  
Songbang Ou ◽  
Ping Liu ◽  
Tao Du ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
De Novo ◽  
Whole Genome ◽  
De Novo Mutations ◽  
Preimplantation Genetic Testing ◽  
Testing Method ◽  
Balanced Translocations

scholarly journals Detection and phasing of single base de novo mutations in biopsies from human in vitro fertilized embryos by advanced whole-genome sequencing

2015 ◽  
Vol 25 (3) ◽  
pp. 426-434 ◽  
Author(s):  
Brock A. Peters ◽  
Bahram G. Kermani ◽  
Oleg Alferov ◽  
Misha R. Agarwal ◽  
Mark A. McElwain ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
De Novo ◽  
Whole Genome ◽  
De Novo Mutations ◽  
Single Base

scholarly journals Whole-genome Sequencing Reveals De-novo Mutations Associated with Nonsyndromic Cleft Lip/Palate

2021 ◽  
Author(s):  
Waheed Awotoye ◽  
Peter A. Mossey ◽  
Jacqueline B. Hetmanski ◽  
Lord Jephthah Joojo Gowans ◽  
Mekonen A. Eshete ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Cleft Lip ◽  
De Novo ◽  
Association Studies ◽  
Whole Genome ◽  
Loss Of Function ◽  
De Novo Mutations ◽  
Pathogenic Variants ◽  
Cleft Lip Palate

Abstract The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact DNMs that contribute to the risk of nsCL/P, we conducted whole genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs that contribute to the risk of nsCL/P. These include novel loss-of-function DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Experimental evidence showed that ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, MINK1, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TTN genes contribute to facial development and mutations in these genes could contribute to CL/P. Association studies have identified TULP4 as a potential cleft candidate gene, while ARHGAP10 interacts with CTNNB1 to control WNT signaling. DLX6, EPHB2, SEMA3C and SEMA4D harbor novel damaging DNMs that may affect their role in neural crest migration and palatal development. This discovery of pathogenic DNMs also confirms the power of WGS analysis of trios in the discovery of potential pathogenic variants.

Whole Genome Sequencing To Identify De Novo Mutations In Bipolar Disorder

2017 ◽  
Vol 27 ◽  
pp. S384
Author(s):  
Fernando Goes ◽  
Mehdi Pirooznia ◽  
Martin Tehan ◽  
Paula Wolyniec ◽  
John McGrath ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
De Novo ◽  
Whole Genome ◽  
De Novo Mutations

scholarly journals Whole Genome Sequencing of a Vietnamese Family from a Dioxin Contamination Hotspot Reveals Novel Variants in the Son with Undiagnosed Intellectual Disability

2018 ◽  
Vol 15 (12) ◽  
pp. 2629 ◽  
Author(s):  
Dang Nguyen ◽  
Hai Nguyen ◽  
Thuy Nguyen ◽  
Thi Nguyen ◽  
Kaoru Nakano ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
De Novo ◽  
Genetic Alterations ◽  
Whole Genome ◽  
Missense Mutations ◽  
De Novo Mutations ◽  
Bioinformatics Analyses ◽  
Dioxin Contamination

Although it has been a half-century since dioxin-contaminated herbicides were used to defoliate the landscape during the Vietnam War, dioxin contamination “hotspots” still remain in Vietnam. Environmental and health impacts of these hotspots need to be evaluated. Intellectual disability (ID) is one of the diseases found in the children of people exposed to the herbicides. This study aims to identify genetic alterations of a patient whose family lived in a dioxin hotspot. The patient’s father had a highly elevated dioxin concentration. He was affected with undiagnosed moderate ID. To analyze de novo mutations and genetic variations, and to identify causal gene(s) for ID, we performed whole genome sequencing (WGS) of the proband and his parents. Two de novo missense mutations were detected, each one in ETS2 and ZNF408 genes, respectively. Compound heterozygosity was identified in CENPF and TTN genes. Existing knowledge on the genes and bioinformatics analyses suggest that EST2, ZNF408, and CENPF might be promising candidates for ID causative genes.

scholarly journals A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies

2018 ◽  
Vol 102 (6) ◽  
pp. 1031-1047 ◽  
Author(s):  
Yuwen Liu ◽  
Yanyu Liang ◽  
A. Ercument Cicek ◽  
Zhongshan Li ◽  
Jinchen Li ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
De Novo ◽  
Whole Genome ◽  
De Novo Mutations ◽  
Risk Genes ◽  
Statistical Framework ◽  
Sequencing Studies

scholarly journals De novo mutations identified by whole-genome sequencing implicate chromatin modifications in obsessive-compulsive disorder

2022 ◽  
Vol 8 (2) ◽  
Author(s):  
Guan Ning Lin ◽  
Weichen Song ◽  
Weidi Wang ◽  
Pei Wang ◽  
Huan Yu ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
De Novo ◽  
Chromatin Modification ◽  
Whole Genome ◽  
Chromatin Modifications ◽  
De Novo Mutations ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

Trio-based whole-genome sequencing identified the role of chromatin modification in OCD pathology.

scholarly journals Effective variant filtering and expected candidate variant yield in studies of rare human disease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Brent S. Pedersen ◽  
Joe M. Brown ◽  
Harriet Dashnow ◽  
Amelia D. Wallace ◽  
Matt Velinder ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Rare Disease ◽  
Genome Sequencing ◽  
Autosomal Dominant ◽  
De Novo ◽  
Autosomal Dominant Inheritance ◽  
Compound Heterozygous ◽  
Whole Genome ◽  
Dominant Inheritance ◽  
Family Based

AbstractIn studies of families with rare disease, it is common to screen for de novo mutations, as well as recessive or dominant variants that explain the phenotype. However, the filtering strategies and software used to prioritize high-confidence variants vary from study to study. In an effort to establish recommendations for rare disease research, we explore effective guidelines for variant (SNP and INDEL) filtering and report the expected number of candidates for de novo dominant, recessive, and autosomal dominant modes of inheritance. We derived these guidelines using two large family-based cohorts that underwent whole-genome sequencing, as well as two family cohorts with whole-exome sequencing. The filters are applied to common attributes, including genotype-quality, sequencing depth, allele balance, and population allele frequency. The resulting guidelines yield ~10 candidate SNP and INDEL variants per exome, and 18 per genome for recessive and de novo dominant modes of inheritance, with substantially more candidates for autosomal dominant inheritance. For family-based, whole-genome sequencing studies, this number includes an average of three de novo, ten compound heterozygous, one autosomal recessive, four X-linked variants, and roughly 100 candidate variants following autosomal dominant inheritance. The slivar software we developed to establish and rapidly apply these filters to VCF files is available at https://github.com/brentp/slivar under an MIT license, and includes documentation and recommendations for best practices for rare disease analysis.

scholarly journals Continuing the sequence? Towards an economic evaluation of whole genome sequencing for the diagnosis of rare diseases in Scotland

2021 ◽  
Author(s):  
Michael Abbott ◽  
Lynda McKenzie ◽  
Blanca Viridiana Guizar Moran ◽  
Sebastian Heidenreich ◽  
Rodolfo Hernández ◽  
...  
Keyword(s):  
Economic Evaluation ◽  
Genetic Testing ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Rare Diseases ◽  
Genomic Medicine ◽  
Future Research ◽  
Clinical Genetics ◽  
Whole Genome ◽  
Peace Of Mind

AbstractNovel developments in genomic medicine may reduce the length of the diagnostic odyssey for patients with rare diseases. Health providers must thus decide whether to offer genome sequencing for the diagnosis of rare conditions in a routine clinical setting. We estimated the costs of singleton standard genetic testing and trio-based whole genome sequencing (WGS), in the context of the Scottish Genomes Partnership (SGP) study. We also explored what users value about genomic sequencing. Insights from the costing and value assessments will inform a subsequent economic evaluation of genomic medicine in Scotland. An average cost of £1,841 per singleton was estimated for the standard genetic testing pathway, with significant variability between phenotypes. WGS cost £6625 per family trio, but this estimate reflects the use of WGS during the SGP project and large cost savings may be realised if sequencing was scaled up. Patients and families valued (i) the chance of receiving a diagnosis (and the peace of mind and closure that brings); (ii) the information provided by WGS (including implications for family planning and secondary findings); and (iii) contributions to future research. Our costings will be updated to address limitations of the current study for incorporation in budget impact modelling and cost-effectiveness analysis (cost per diagnostic yield). Our insights into the benefits of WGS will guide the development of a discrete choice experiment valuation study. This will inform a user-perspective cost–benefit analysis of genome-wide sequencing, accounting for the broader non-health outcomes. Taken together, our research will inform the long-term strategic development of NHS Scotland clinical genetics testing services, and will be of benefit to others seeking to undertake similar evaluations in different contexts.

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