Skip directly to search Skip directly to A to Z list Skip directly to navigation Skip directly to page options Skip directly to site content


Hot Topics of the Day|PHGKB
Search PHGKB:

Archive

Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

Sign up MyPHGKB to receive the daily hot topic email alert.

Search Archive:
Archived Hot Topics of the Day By Date
100 hot topic(s) found with the query "Whole exome sequencing "

A cost-effective sequencing method for genetic studies combining high-depth whole exome and low-depth whole genome.
Claude Bhérer et al. NPJ Genom Med 2024 2 (1) 8 (Posted: Feb 09, 2024 10AM)

From the abstract: " Whole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high-depth WGS, most large-scale genetic association studies use genotyping arrays or high-depth whole exome sequencing (WES). Here we propose a cost-effective method which we call “Whole Exome Genome Sequencing” (WEGS), that combines low-depth WGS and high-depth WES with up to 8 samples pooled and sequenced simultaneously (multiplexed)."

Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders.
Mario Cesare Nurchis et al. JAMA Netw Open 2024 1 (1) e2353514 (Posted: Jan 30, 2024 8AM)

From the abstract: "Is whole-genome sequencing (WGS) more cost-effective than whole-exome sequencing for children with suspected genetic disorders? The results of this economic evaluation of a cohort of 870 pediatric patients suggest that adopting WGS as a first-tier strategy would be cost-effective at a willingness-to-pay threshold of €30 000 to €50 000 (US $32?625-$54?375), specifically for the diagnosis of severely ill infants with suspected genetic disorders. ng These findings suggest that wider use of WGS may minimize diagnostic delays and facilitate timely implementation of appropriate treatments. "

Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk
N Wilcox et al, Nat Genetics, August 17, 2023 (Posted: Aug 18, 2023 7AM)

To evaluate the role of rare coding variants more comprehensively, we performed a meta-analysis across three large whole-exome sequencing datasets, containing 26,368 female cases and 217,673 female controls. Burden tests were performed for protein-truncating and rare missense variants in 15,616 and 18,601 genes, respectively. Associations between protein-truncating variants and breast cancer were identified for the following six genes at exome-wide significance (P?<?2.5?×?10-6): the five known susceptibility genes ATM, BRCA1, BRCA2, CHEK2 and PALB2, together with MAP3K1.

Epilepsies of presumed genetic etiology show enrichment of rare variants that occur in the general population.
Linnaeus Bundalian et al. Am J Hum Genet 2023 6 (Posted: Jun 29, 2023 8AM)

Previous studies suggested that severe epilepsies, e.g., developmental and epileptic encephalopathies (DEEs), are mainly caused by ultra-rare de novo genetic variants. For milder disease, rare genetic variants could contribute to the phenotype. To determine the importance of rare variants for different epilepsy types, we analyzed a whole-exome sequencing cohort of 9,170 epilepsy-affected individuals and 8,436 control individuals. Here, we separately analyzed three different groups of epilepsies: severe DEEs, genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE).

Genetic testing in monogenic early-onset atrial fibrillation.
Brandon Chalazan et al. Eur J Hum Genet 2023 5 (Posted: May 23, 2023 11AM)

We aim to determine the prevalence of likely pathogenic and pathogenic variants from AF genes with robust evidence in a well phenotyped early-onset AF population. We performed whole exome sequencing on 200 early-onset AF patients. Variants from exome sequencing in affected individuals were filtered in a multi-step process, prior to undergoing clinical classification using current ACMG/AMP guidelines. There was a 3.0% diagnostic yield for identifying a likely pathogenic or pathogenic variant across AF genes with robust gene-to-disease association evidence.

Meta-analysis of the diagnostic and clinical utility of exome and genome sequencing in pediatric and adult patients with rare diseases across diverse populations
C Ching et al, Genetics in Medicine, May 13, 2023 (Posted: May 14, 2023 9AM)

This meta-analysis aims to compare the diagnostic and clinical utility of whole-exome sequencing (WES) versus whole-genome sequencing (WGS) in pediatric and adult patients with rare diseases across diverse populations. One-hundred-and-sixty-one studies across 31 countries/regions were eligible, featuring 50,417 probands of diverse populations. Diagnostic rates of WES (0.38, 95% CI 0.36-0.40) and WGS (0.34, 95% CI 0.30-0.38) were similar.

An Explainable Host Genetic Severity Predictor Model for COVID-19 Patients
A Onoja et al, MEDRXIV, March 9, 2023 (Posted: Mar 10, 2023 3PM)

A host genetic severity predictor (HGSP) model was developed by combining several state-of-the-art machine learning algorithms (decision tree-based models: Random Forest and XGBoost classifiers). These models were trained using a genetic Whole Exome Sequencing (WES) dataset and clinical covariates (age and gender) formulated from a 5-fold stratified cross-validation computational strategy to randomly split the dataset to overcome model instability. Our study validated the HGSP model based on the 18 features (i.e., 16 identified candidate genetic variants and 2 covariates.

Landscape of pathogenic mutations in premature ovarian insufficiency.
Hanni Ke et al. Nature medicine 2023 2 (Posted: Feb 04, 2023 7AM)

Premature ovarian insufficiency (POI) is a major cause of female infertility due to early loss of ovarian function. POI is a heterogeneous condition, and its molecular etiology is unclear. To identify genetic variants associated with POI, here we performed whole-exome sequencing in a cohort of 1,030 patients with POI. We detected 195 pathogenic/likely pathogenic variants in 59 known POI-causative genes, accounting for 193 (18.7%) cases.

Medullary Thyroid Carcinoma and Population Screening-The Promise and Pitfalls of Genetic Testing.
Davies Louise et al. JAMA otolaryngology-- head & neck surgery 2023 1 (Posted: Jan 11, 2023 6AM)

Geisinger invited its members to consent to whole-exome sequencing and linked the findings with electronic health record information to identify future targets for medication development and other interventions to improve population health. Patients would be notified through a specifically established MyCode counseling program if they were found to have known, actionable genetic variants. The program has been popular; more than 270?000 Geisinger members have now signed up. The expected rate of actionable variants is approximately 3.5%. The popularity of the program suggests that as broader testing begins to penetrate US health care outside of specialized programs like the Geisinger one, we can expect to see many more patients in our offices who present after having learned they have one of these variants.

The phenotypic spectrum associated with loss-of-function variants in monogenic epilepsy genes in the general population
V Smuk et al, EJHG, October 17, 2022 (Posted: Oct 17, 2022 6AM)

We selected 127 established monogenic epilepsy genes and explored rare loss-of-function (LoF) variant associations with 3700 phenotypes across 281,850 individuals from the UK Biobank with whole-exome sequencing data. For 5.5% of epilepsy genes, we found significant associations of LoF variants with non-epilepsy phenotypes, mostly related to mental health. These findings suggest that LoF variants in epilepsy genes are associated with neurological or psychiatric phenotypes in the general population

Burden of Rare Genetic Variants in Spontaneous Coronary Artery Dissection With High-risk Features
Y Wang et al, JAMA Cardiology, September 15, 2022 (Posted: Sep 16, 2022 8AM)

In a whole-exome sequencing genetic study, 17% of individuals with high-risk SCAD had rare variants in vascular connective tissue disease genes, representing a significant enrichment compared with the Genome Aggregation Database (gnomAD), especially in COL3A1 and Loeys-Dietz syndrome genes. Rare variants in genes recently discovered by genome-wide association study, ADAMTSL4 and LRP1, identified in 6% of the cohort, were also enriched.

Neurofibromatosis Type 1 and Risk of Skin Cancer
J Trinh et al, JAMA Dermatology, August 24, 2022 (Posted: Aug 24, 2022 1PM)

This study found increased odds of melanoma, BCC, and SCC in patients with NF1. Whole-exome sequencing has established NF1 as the third most frequently mutated gene in melanomas.3 About 12% to 18% of melanomas and 45% to 93% of desmoplastic melanomas harbor NF1 alterations.

Development of an extensive workflow for comprehensive clinical pharmacogenomic profiling: lessons from a pilot study on 100 whole exome sequencing data
A Tafazoli et al, The PGX Journal, August 13 , 2022 (Posted: Aug 13, 2022 6PM)

This pilot study is aimed at implementing an approach for comprehensive clinical pharmacogenomics (PGx) profiling. Fifty patients with cardiovascular diseases and 50 healthy individuals underwent whole-exome sequencing. Data on 1800 PGx genes were extracted and analyzed through deep filtration separately. Theoretical drug induced phenoconversion was assessed for the patients, using sequence2script. In total, 4539 rare variants (including 115 damaging non-synonymous) were identified.

Finding Ways to Improve Patients’ Cancer Immunotherapy Response
HD Larkin, JAMA, August 9, 2022 (Posted: Aug 09, 2022 11AM)

An investigational tool using whole-exome sequencing (WES) more accurately identified genes and pathways that predict whether patients with cancer will respond to immune checkpoint blockade (ICB) than current tumor mutation burden (TMB) tests alone, a new research study reported. TMB is often used to determine ICB eligibility and is generally calculated from a few hundred genes. The researchers sought to improve its performance by broadening analysis to the nearly 20?000 genes consistently captured by WES.

The sequences of 150,119 genomes in the UK Biobank
BV Halldorsson et al, Nature, July 20, 2022 (Posted: Jul 20, 2022 4PM)

Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank3. This constitutes a set of high-quality variants, including 585,040,410 single-nucleotide polymorphisms, representing 7.0% of all possible human single-nucleotide polymorphisms, and 58,707,036 indels. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large-scale whole-genome sequencing studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on whole-exome sequencing and/or imputation.

Comprehensive profiling of 1015 patients’ exomes reveals genomic-clinical associations in colorectal cancer
Q Zhao et al, Nature Comms, April 29, 2022 (Posted: Apr 29, 2022 0PM)

The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST, DAPK1, CR2, KIF16B, NPIPB15, SYTL2, ZNF91, and KIAA0586. With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics.

Clinical implementation of RNA sequencing for Mendelian disease diagnostics
VA Yepez et al, Genome Medicine, April 5, 2022 (Posted: Apr 06, 2022 10AM)

Lack of functional evidence hampers variant interpretation, leaving a large proportion of individuals with a suspected Mendelian disorder without genetic diagnosis after whole genome or whole exome sequencing (WES). Research studies advocate to further sequence transcriptomes to directly and systematically probe gene expression defects. We implemented an automated RNA-seq protocol and a computational workflow with which we analyzed skin fibroblasts of 303 individuals with a suspected mitochondrial disease that previously underwent WES.

Clinical pharmacogenetic analysis in 5,001 individuals with diagnostic Exome Sequencing data
J Lanillos et al, NPJ Genomic Medicine, February 18, 2022 (Posted: Feb 19, 2022 7AM)

we carried out a systematic analysis based on 5001 Spanish or Latin American individuals with diagnostic exome data, either Whole Exome Sequencing (80%), or the so-called Clinical Exome Sequencing (20%) (60?Mb and 17?Mb, respectively), to provide with global and gene-specific clinical pharmacogenetic utility data. 788 pharmacogenetic alleles, distributed through 19 genes included in Clinical Pharmacogenetics Implementation Consortium guidelines were analyzed. Each individual carried in average 2.2 alleles and overall 95% (n?=?4646) of the cohort could be informed of at least one actionable pharmacogenetic phenotype. Differences in variant allele frequency were observed among the populations studied and the corresponding gnomAD population for 7.9% of the variants.

Analysis of rare genetic variation underlying cardiometabolic diseases and traits among 200,000 individuals in the UK Biobank
SJ Jurgens et al, Nature Genetics, February 17, 2022 (Posted: Feb 18, 2022 7AM)

Cardiometabolic diseases are the leading cause of death worldwide. Despite a known genetic component, our understanding of these diseases remains incomplete. Here, we analyzed the contribution of rare variants to 57 diseases and 26 cardiometabolic traits, using data from 200,337 UK Biobank participants with whole-exome sequencing. We identified 57 gene-based associations.

Whole-exome sequencing improves the diagnosis and care of men with non-obstructive azoospermia.
Kherraf Zine-Eddine et al. American journal of human genetics 2022 2 (Posted: Feb 17, 2022 11AM)

Exome sequencing was performed on 96 NOA-affected individuals negative for routine genetic tests. Bioinformatics analysis was limited to a panel of 151 genes selected as known causal or candidate genes for NOA. Only highly deleterious homozygous or hemizygous variants were retained as candidates. A likely causal defect was identified in 16 genes in a total of 22 individuals (23%).

Somatic mutational profiles and germline polygenic risk scores in human cancer.
Liu Yuxi et al. Genome medicine 2022 2 (1) 14 (Posted: Feb 16, 2022 8AM)

We used polygenic risk scores (PRS) to summarize common germline variation associated with cancer risk and other cancer-related traits and examined the association between somatic mutational profiles and germline PRS in 12 cancer types from The Cancer Genome Atlas. Somatic mutational profiles were constructed from whole-exome sequencing data of primary tumors. Our analysis suggests that there are robust associations between tumor somatic mutational profiles and germline PRS. These may reflect the mechanisms through hormone regulation and immune responses that contribute to cancer etiology and drive cancer progression.

A massive effort links protein-coding gene variants to health
Y Okada et al, Nature, October 25, 2021 (Posted: Oct 25, 2021 1PM)

The protein-coding portions of more than 450,000 individuals’ genomes have been sequenced, and analyzed together with the individuals’ health data, revealing rare and common gene variants linked to various health-related traits. Initial analysis of data from the UK Biobank3 included genetic information that was limited to common variants already known to occur in a relatively large proportion of individuals (for example, more than 1% of the tested population). However, such variants are probably only the tip of the iceberg of the total variation in the human exome. The use of whole-exome sequencing (WES) technology was the key to obtaining detailed information about exome variation.

Lessons learned from unsolicited findings in clinical exome sequencing of 16,482 individuals
V van der Shoot et al, EJHG, October 25, 2021 (Posted: Oct 25, 2021 10AM)

We here evaluated UFs identified during a 5-year period in which 16,482 index patients received clinical whole-exome sequencing (WES). UFs were identified in 0.58% (95/16,482) of index patients, indicating that the overall frequency of UFs in clinical WES is low. Fewer UFs were identified using restricted disease-gene panels (0.03%) than when using whole-exome/Mendeliome analysis (1.03%). The UF was disclosed to 86 of 95 individuals, for reasons of medical actionability. Only 61% of these UFs reside in a gene that is listed on the “ACMG59”-list.

The power of large-scale exome sequencing
L Koch, Nat Rev Genetics July 16, 2021 (Posted: Jul 17, 2021 7AM)

Over the past decade, the ability to investigate protein-coding regions using high-throughput sequencing has been a cornerstone of human disease genetics, driving the discovery of genes associated with many diseases. When initially conceived, whole-exome sequencing (WES) focused on identifying mutations that caused rare monogenic disorders.

New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin
X Liu et al, The Pharmacogenomics Journal, June 22, 2021 (Posted: Jun 23, 2021 8AM)

This study aims to identify new genetic variants associated with MACE end point during the 18-month follow-up period by a two-stage large-scale sequencing data, including high-depth whole exome sequencing of 168 patients in the discovery cohort and high-depth targeted sequencing of 1793 patients in the replication cohort. We discovered eight new genotypes and their genes associated with MACE in patients with ACS.

Solving the unsolved rare diseases in Europe
E Graessner et al, EJHG, June 18, 2021 (Posted: Jun 18, 2021 6AM)

Getting a diagnosis can be a long and arduous process for a patient with a rare disease. Some patients take months, years, or even their entire lives to receive a proper diagnosis and occasionally corresponding therapy. Around 50 percent of patients with a rare disease remain undiagnosed even in advanced expert clinical settings where Whole Exome Sequencing (WES) is applied routinely as a diagnostic approach.

Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms
H Luo et al, EJHG, April 19, 2021 (Posted: Apr 19, 2021 9AM)

We conducted whole-exome sequencing in 233 hospitalized COVID-19 patients and identified four PID gene (UNC13D, AP3B1, RNF168, DHX58) variants were significantly enriched in COVID-19 patients experiencing severe cytokine storms. The total percentage of COVID-19 patients with variants in UNC13D or AP3B1, two typical HLH genes, was dramatically higher in high-level cytokine group than in low-level group (33.3 vs. 5.7%, P?<?0.001).

Germline Whole-Exome Sequencing Reveals the Potential Role of Hereditary Predisposition and Therapeutic Implications in SCLC
ASCO Post, February 4, 2021 (Posted: Feb 07, 2021 7AM)

A new study shows that there may be an inherited predisposition for small cell lung cancer (SCLC). The findings lay the foundation for understanding the interaction between genotype and tobacco exposure in exacerbating SCLC risk, as well as potential therapeutic implications. Because tobacco is the dominant carcinogen, secondary causes of lung cancer are often diminished in perceived importance. SCLC is almost exclusively related to tobacco and comprises 15-20% of all lung cancers.

Whole-exome sequencing reveals germline-mutated small cell lung cancer subtype with favorable response to DNA repair–targeted therapies
C Tlemsani et al, Sci Trans Med, January 27, 2021 (Posted: Jan 28, 2021 8AM)

Small cell lung cancer (SCLC) is generally regarded as a smoker’s cancer. However, the genetic factors that affect susceptibility to SCLC have not been fully evaluated. The authors performed whole-exome sequencing on the germ lines of a cohort of participants with SCLC, finding that almost half the cohort carried deleterious variants in cancer-predisposing genes. Those with pathogenic germline variants had better response to platinum-based chemotherapy.

Parents, their children, whole exome sequencing and unsolicited findings: growing towards the child's future autonomy.
Tibben Aad et al. European journal of human genetics : EJHG 2021 Jan (Posted: Jan 19, 2021 8AM)

HLA-C* 04:01 is a Genetic Risk Allele for Severe Course of COVID-19
J Weiner et al, MEDRXIV, December 24, 2020 (Posted: Dec 25, 2020 7AM)

We analyzed a total of 332 samples. First, we enrolled 233 patients in Germany, Spain, and Switzerland for HLA and whole exome sequencing. We identified HLA-C* 04:01 as a novel genetic predictor for severe clinical course in COVID-19. Carriers of HLA-C* 04:01 had twice the risk of intubation when infected with SARS-CoV-2 (hazard ratio 2.1, adjusted p-value=0.0036). Importantly, these findings were successfully replicated in an independent data set.

Assessing the Role of Rare Genetic Variation in Patients With Heart Failure.
Povysil Gundula et al. JAMA cardiology 2020 Dec (Posted: Dec 17, 2020 8AM)

In this analysis of 5942 patients with heart failure and 13 156 controls using whole-exome sequencing, a significant enrichment of rare protein-truncating variants in the TTN gene and in general an increased burden of mendelian cardiomyopathy variants was demonstrated in patients with heart failure compared with controls.

Exome Sequencing as a Potential Diagnostic Adjunct in Sporadic Congenital Hydrocephalus.
Sullivan William et al. JAMA pediatrics 2020 Nov (Posted: Nov 17, 2020 8AM)

We applied whole-exome sequencing (WES) to what is, to our knowledge, the largest cohort of neurosurgically treated CH probands collected to date (475 probands and 284 case-parent trios). We uncovered 5 novel and 7 total protein-damaging L1CAM mutations (1.47% of our cohort) in male CH probands.

Re-analysis of whole-exome sequencing data uncovers novel diagnostic variants and improves molecular diagnostic yields for sudden death and idiopathic diseases.
Salfati Elias L et al. Genome medicine 2019 Dec (1) 83 (Posted: Dec 19, 2019 9AM)

Initial analysis revealed diagnostic variants in 13 rare disease cases (25.4%) and 5 sudden death cases (10%). Re-analysis resulted in the identification of additional diagnostic variants in 3 rare disease cases (5.9%) and 1 sudden unexplained death case (2%), which increased our molecular diagnostic yield to 31.4% and 12%, respectively.

Pilot study of EVIDENCE: High diagnostic yield and clinical utility of whole exome sequencing using an automated interpretation system for patients with suspected genetic disorders
BGH Seo et al, IORXIV, November 2019 (Posted: Nov 18, 2019 9AM)

A new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 51% improvement in diagnostic yield. DNA from 330 probands (age range, 0–68 years) with suspected genetic disorders were subjected to WES. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments.

Integration of Large-Scale Genomic Data Sources With Evolutionary History Reveals Novel Genetic Loci for Congenital Heart Disease
E Fotieu et al, Circulation Genomics and Precision Medicine, October 2019 (Posted: Oct 19, 2019 7AM)

We compared copy number variants present in 4634 nonsyndromic CHD cases derived from publicly available data resources and the literature, and >27?000 healthy individuals. We analyzed deletions and duplications independently and identified copy number variant regions exclusive to cases. These data were integrated with whole-exome sequencing data.

NSIGHT2 Trial Finds Whole-Genome Sequencing Has High Analytical Performance
GenomeWeb, September 26, 2019 (Posted: Sep 27, 2019 10AM)

Whole-genome sequencing can be a viable first-line diagnostic testing option. A study compared the effectiveness of rapid whole-genome or whole-exome sequencing in seriously ill infants with unknown diseases. The research team enrolled more than 200 sick infants into their study to undergo sequencing.

A polygenic predictor of treatment-resistant depression using whole exome sequencing and genome-wide genotyping
C Fabri et al, MedRXIV, September 20, 2019 (Posted: Sep 20, 2019 9AM)

Treatment-resistant depression occurs in ~30% of patients with major depressive disorder (MDD). Whole exome sequencing and genome-wide genotyping were performed in 1320 MDD patients. Response to the first pharmacological treatment was compared to non-response to one treatment and non-response to two or more treatments.

Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals
Epi25 collaborative, AJHG, July 18, 2019 (Posted: Jul 19, 2019 8AM)

The study performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. Compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy.

Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype.
Ma Yiyi et al. JAMA neurology 2019 Jun (Posted: Jun 11, 2019 7AM)

Application whole exome sequencing for the clinical molecular diagnosis of patients with Duchenne muscular dystrophy; identification of four novel nonsense mutations in four unrelated Chinese DMD patients.
Zhang Yan et al. Molecular genetics & genomic medicine 2019 Apr e622 (Posted: Apr 03, 2019 9AM)

Whole exome sequencing and characterization of coding variation in 49,960 individuals in the UK Biobank
CV Van Hout et al, BioxRIV preprints, March 9, 2019 (Posted: Mar 10, 2019 0PM)

Advancing Personalized Medicine Through the Application of Whole Exome Sequencing and Big Data Analytics
P Sewinski et al, Front in Genetics, February 2019 (Posted: Mar 03, 2019 10AM)

Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study.
Petrovski Slavé et al. Lancet (London, England) 2019 Jan (Posted: Feb 05, 2019 11AM)

Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients.
Mann Nina et al. Journal of the American Society of Nephrology : JASN 2019 Jan (Posted: Jan 23, 2019 1PM)

Evaluation of whole exome sequencing as an alternative to BeadChip and whole genome sequencing in human population genetic analysis.
Maróti Zoltán et al. BMC genomics 2018 Oct 19(1) 778 (Posted: Oct 31, 2018 8AM)

Identifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES)
GKC Leung et al, BMC Medical Genomics, October 25, 2018 (Posted: Oct 30, 2018 0PM)

A stroke gene panel for whole-exome sequencing
A Ilinca et al, EJHG, October 24, 2018 (Posted: Oct 24, 2018 3PM)

Clinical whole-exome sequencing results impact medical management.
Niguidula Nancy et al. Molecular genetics & genomic medicine 2018 Oct (Posted: Oct 17, 2018 8AM)

Utilizing Whole-Exome Sequencing to Characterize the Phenotypic Variability of Sickle Cell Disease.
Alsultan Abdulrahman et al. Genetic testing and molecular biomarkers 2018 Sep (Posted: Sep 12, 2018 9AM)

Whole-exome sequencing in 20,197 persons for rare variants in Alzheimer's disease.
Raghavan Neha S et al. Annals of clinical and translational neurology 2018 Jul 5(7) 832-842 (Posted: Jul 18, 2018 9AM)

Whole Exome Sequencing in 20,197 Persons for Rare Variants in Alzheimer Disease
NS Raghavan et al, BioRXIV, Apr 20, 2018 (Posted: Apr 22, 2018 0PM)

Beyond Gene Panels: Whole Exome Sequencing for Diagnosis of Congenital Heart Disease.
Paige Sharon L et al. Circulation. Genomic and precision medicine 2018 Mar 11(3) e002097 (Posted: Mar 21, 2018 5PM)

Whole Exome Sequencing: Applications in Prenatal Genetics.
Jelin Angie C et al. Obstetrics and gynecology clinics of North America 2018 Mar 45(1) 69-81 (Posted: Feb 21, 2018 10AM)

Effect of Whole Exome Sequencing in Diagnosis of Inborn Errors of Metabolism and Neurogenetic Disorders.
Shakiba Marjan et al. Iranian journal of child neurology 2018 12(1) 7-15 (Posted: Jan 31, 2018 9AM)

Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study
S Lata et al, Ann Int Med, Dec 5, 2017 (Posted: Dec 05, 2017 10AM)

Intersociety policy statement on the use of whole-exome sequencing in the critically ill newborn infant.
Borghesi Alessandro et al. Italian journal of pediatrics 2017 Nov 43(1) 100 (Posted: Nov 08, 2017 9AM)

Whole exome sequencing in 342 congenital cardiac left sided lesion cases reveals extensive genetic heterogeneity and complex inheritance patterns
AH Li et al, Genome Medicine, Oct 2017 (Posted: Nov 02, 2017 9AM)

How do providers discuss the results of pediatric exome sequencing with families?
Walser Sarah A et al. Personalized medicine 2017 Sep 14(5) 409-422 (Posted: Oct 04, 2017 10AM)

A Time to Sequence
S Baxter et al, JAMA Pediatrics, Oct 2, 2017 (Posted: Oct 02, 2017 6PM)

Use of Exome Sequencing for Infants in Intensive Care Units
L Meng et al, JAMA Pediatrics, Oct 2, 2017 (Posted: Oct 02, 2017 6PM)

Application of whole-exome sequencing to direct the specific functional testing and diagnosis of rare inherited bleeding disorders in patients from the Öresund Region, Scandinavia.
Leinøe Eva et al. British journal of haematology 2017 Jul (Posted: Aug 02, 2017 8AM)

Diagnostic Impact and Cost-effectiveness of Whole-Exome Sequencing for Ambulant Children With Suspected Monogenic Conditions
TY Tan et al, JAMA Pediatrics, July 31, 2017 (Posted: Jul 31, 2017 1PM)

Whole exome sequencing and DNA methylation analysis in a clinical amyotrophic lateral sclerosis cohort.
Garton Fleur C et al. Molecular genetics & genomic medicine 2017 Jul 5(4) 418-428 (Posted: Jul 26, 2017 9AM)

Promises, Pitfalls and Practicalities of Prenatal Whole Exome Sequencing.
Best Sunayna et al. Prenatal diagnosis 2017 Jun (Posted: Jul 03, 2017 6PM)

Whole exome sequencing: a state-of-the-art approach for defining (and exploring!) genetic landscapes in pediatric nephrology.
Gulati Ashima et al. Pediatric nephrology (Berlin, Germany) 2017 Jun (Posted: Jul 03, 2017 6PM)

Whole exome sequencing in clinical genetics - a health economic evaluation
GS Sagoo et al, PHG Foundation, June 2017 (Posted: Jul 03, 2017 6PM)

Whole exome sequencing in clinical genetics: health economic evaluation
PHG Foundation, May 2017 (Posted: Jul 03, 2017 6PM)

Stakeholder views on secondary findings in whole-genome and whole-exome sequencing: a systematic review of quantitative and qualitative studies.
Mackley Michael P et al. Genetics in medicine : official journal of the American College of Medical Genetics 2017 Mar 19(3) 283-293 (Posted: Apr 26, 2017 9AM)

Application of Whole Exome Sequencing in the Clinical Diagnosis and Management of Inherited Cardiovascular Diseases in Adults.
Seidelmann Sara B et al. Circulation. Cardiovascular genetics 2017 Feb 10(1) (Posted: Apr 19, 2017 8AM)

Prospective comparison of the cost-effectiveness of clinical whole-exome sequencing with that of usual care overwhelmingly supports early use and reimbursement
Z Stark et al, Genetics in Medicine, January 26, 2017 (Posted: Jan 26, 2017 11AM)

Analysis of more than 50,000 genomes hints at new disease-causing genes
J Kaiser, Science, December 23, 2016 (Posted: Dec 24, 2016 3PM)

Exome Study Reveals Novel Disease-Linked Alleles
A Azvolinsky, the Scientist, December 23, 2016 (Posted: Dec 23, 2016 2PM)

“Pheno”menal value for human health
DJ Rader et al, Science, December 22, 2016 (Posted: Dec 22, 2016 5PM)

Regulating whole exome sequencing as a diagnostic test.
Lapin Valentina et al. Human genetics 2016 Jun (6) 655-73 (Posted: Nov 02, 2016 6AM)

Family Based Whole Exome Sequencing Reveals the Multifaceted Role of Notch Signaling in Congenital Heart Disease
C Preus et al, PLOS Genetics, October 2016 (Posted: Oct 20, 2016 3PM)

The clinical utility of whole-exome sequencing in the context of rare diseases - the changing tides of medical practice.
Nguyen M T et al. Clinical genetics 2015 Oct 88(4) 313-9 (Posted: Jun 29, 2016 1PM)

Whole-exome sequencing to identify genetic risk variants underlying inhibitor development in severe hemophilia A patients
MM Gorski et al, Blood, March, 2016 (Posted: Apr 20, 2016 3PM)

Whole-exome sequencing for clinical diagnostics
L Koch, Nature Reviews Genetics, March 2016 (Posted: Mar 22, 2016 8AM)

Whole-exome sequencing: A rational approach for 'diagnostic odyssey' patients
Medical Xpress, March 1, 2016 (Posted: Mar 02, 2016 10AM)

Not the End of the Odyssey: Parental Perceptions of Whole Exome Sequencing (WES) in Pediatric Undiagnosed Disorders.
Rosell Allyn McConkie et al. Journal of genetic counseling 2016 Feb (Posted: Feb 17, 2016 0PM)

Implications of direct-to-consumer whole-exome sequencing in South Africa.
Lombard Zané et al. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 2016 106(2) 139-40 (Posted: Feb 03, 2016 3PM)

Diagnostic Yield of Clinical Tumor and Germline Whole-Exome Sequencing for Children With Solid Tumors
D Williams-Parson et al, JAMA Oncology, January 28, 2016 (Posted: Jan 29, 2016 11AM)

Whole-exome Sequencing Analysis Identifies Mutations in the EYS Gene in Retinitis Pigmentosa in the Indian Population.
Di Yanan et al. Scientific reports 2016 19432 (Posted: Jan 27, 2016 1PM)

Molecular diagnostic experience of whole-exome sequencing in adult patients.
Posey Jennifer E et al. Genetics in medicine : official journal of the American College of Medical Genetics 2015 Dec (Posted: Dec 09, 2015 9AM)

Clinical application of whole-exome sequencing across clinical indications.
Retterer Kyle et al. Genetics in medicine : official journal of the American College of Medical Genetics 2015 Dec (Posted: Dec 07, 2015 8AM)

Whole-Exome Sequencing in Familial Parkinson Disease.
Farlow Janice L et al. JAMA neurology 2015 Nov 1-8 (Posted: Nov 30, 2015 9AM)

Whole-Exome Sequencing of 10 Scientists: Evaluation of the Process and Outcomes.
Lindor Noralane M et al. Mayo Clinic proceedings 2015 Oct 90(10) 1327-37 (Posted: Oct 06, 2015 5PM)

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
HF Zheng et al. Nature, September 14, 2015 (Posted: Sep 15, 2015 10AM)

The extent to which low©\frequency (minor allele frequency (MAF) between 1¨C5%) and rare (MAF&#8201;¡Ü&#8201;1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants1, 2, 3, 4, 5, 6, 7, 8, as well as rare, population©\specific, coding variants9. Here we identify novel non©\coding genetic variants with large effects on BMD (ntotal&#8201;=&#8201;53,236) and fracture (ntotal&#8201;=&#8201;508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole©\genome sequencing (n&#8201;=&#8201;2,882 from UK10K (ref. 10); a population©\based genome sequencing consortium), whole©\exome sequencing (n&#8201;=&#8201;3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n&#8201;=&#8201;26,534), and de novo replication genotyping (n&#8201;=&#8201;20,271). We identified a low©\frequency non©\coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF&#8201;=&#8201;1.6%, replication effect size&#8201;=&#8201;+0.20 s.d., Pmeta&#8201;=&#8201;2&#8201;¡Á&#8201;10&#8722;14), which was also associated with a decreased risk of fracture (odds ratio&#8201;=&#8201;0.85; P&#8201;=&#8201;2&#8201;¡Á&#8201;10&#8722;11; ncases&#8201;=&#8201;98,742 and ncontrols&#8201;=&#8201;409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low©\frequency non©\coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF&#8201;=&#8201;1.2%, replication effect size&#8201;=&#8201;+0.41 s.d., Pmeta&#8201;=&#8201;1&#8201;¡Á&#8201;10&#8722;11). In general, there was an excess of association signals arising from deleterious coding and conserved non©\coding variants. These findings provide evidence that low©\frequency non©\coding variants have large effects on BMD and fracture, thereby providing rationale for whole©\genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder
K Tammimies et al. JAMA, September 1, 2015 (Posted: Sep 01, 2015 2PM)

Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care.
Sawyer Sarah L et al. Clin. Genet. 2015 Aug 18. (Posted: Aug 19, 2015 1PM)

Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons
G Nicolas, Eur J Human Genetic, August 5, 2015 (Posted: Aug 05, 2015 1PM)

Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region, Sri Lanka.
Nanayakkara Shanika et al. Environ Health Prev Med 2015 Jun 25. (Posted: Jun 30, 2015 3PM)

The Impact of DNA Input Amount and DNA source on the Performance of Whole-Exome Sequencing in Cancer Epidemiology
W Zhu et al. CEBP, May 2015 (Posted: May 22, 2015 6PM)

Whole-exome sequencing and its impact in hereditary hearing loss.
Atik Tahir et al. Genet Res (Camb) 2015 e4 (Posted: May 01, 2015 9AM)

Clinical whole exome sequencing in child neurology practice.
Srivastava Siddharth et al. Ann. Neurol. 2014 Oct (4) 473-83 (Posted: Mar 25, 2015 10AM)

Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy.
McMichael G et al. Mol. Psychiatry 2015 Feb (2) 176-82 (Posted: Mar 25, 2015 10AM)

Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios.
Zhu Xiaolin et al. Genet. Med. 2015 Jan 15. (Posted: Mar 19, 2015 5PM)

Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray.
Bayer D K et al. Clin. Exp. Immunol. 2014 Dec (3) 459-69 (Posted: Mar 05, 2015 0PM)

Molecular findings among patients referred for clinical whole-exome sequencing.
Yang Yaping et al. JAMA 2014 Nov 12. (18) 1870-9 (Posted: Feb 12, 2015 8AM)

more


Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
TOP