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48 hot topic(s) found with the query "Copy number variants"

Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease.
Gabrielle Lemire et al. Am J Hum Genet 2024 4 (Posted: Apr 09, 2024 8AM)

From the abstract: "Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing The addition of CNV detection to exome analysis identified causal CNVs for 171 families (2.6%). "

Genomic analysis of 116 autism families strengthens known risk genes and highlights promising candidates
M Viggiano et al, NPJ Genomic Medicine, March 22, 2024 (Posted: Mar 23, 2024 6AM)

From the abstract: "Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic component in which rare variants contribute significantly to risk. We performed whole genome and/or exome sequencing (WGS and WES) and SNP-array analysis to identify both rare sequence and copy number variants (SNVs and CNVs) in 435 individuals from 116 ASD families. We identified 37 rare potentially damaging de novo SNVs (pdSNVs) in the cases (n?=?144). "

Evidence from 2100 index cases supports genome sequencing as a first-tier genetic test
F Guo et al, Genetics in Medicine, October 12, 2023 (Posted: Oct 13, 2023 1PM)

From the abstract: "Genome sequencing (GS) is one of the most comprehensive assays that interrogate single nucleotide variants, copy number variants, mitochondrial variants, repeat expansions, and structural variants in one assay. Despite the clear technical superiority, the full clinical utility of GS has yet to be determined. The overall diagnostic yield was 28% (585/2100). The diagnostic yield for GS as the first-tier test was 26% (294/1146). Among cases with prior non-diagnostic genetic tests, GS provided a diagnosis for 27% (247/910) of cases. "

Utility of Exome Sequencing for Diagnosis in Unexplained Pediatric-Onset Epilepsy.
Hyun Yong Koh et al. JAMA Netw Open 2023 7 (7) e2324380 (Posted: Jul 21, 2023 7AM)

What are the diagnostic yield and clinical utility of genetic sequencing for patients with unexplained pediatric epilepsy? This cohort study of 522 children with previously unexplained epilepsy used exome sequencing to identify and clinically confirm diagnostic results for 100 children, including 89 with single nucleotide variants and 11 with copy number variants. Individuals with earlier seizure onset, intellectual disability, and motor impairment were more likely to have diagnostic results, and at least 29 patients had changes in treatment, surveillance, or prognosis based on their genetic diagnoses.

Copy number variants from 4800 exomes contribute to ~7% of genetic diagnoses in movement disorders, muscle disorders and neuropathies
M Pennings et al, EJHG, February 13, 2023 (Posted: Feb 14, 2023 7AM)

In this study, CNVs were extracted from clinical exome sequencing reports of 4800 probands primarily with a movement disorder, myopathy or neuropathy. In 88 (~2%) probands, phenotype-matching CNVs were detected, representing ~7% of genetically confirmed cases. CNVs varied from involvement of over 100 genes to single exons and explained X-linked, autosomal dominant, or - recessive disorders, the latter due to either a homozygous CNV or a compound heterozygous CNV with a sequence variant on the other allele.

Rare and common autism risk variants converge across 16p.
Won Hyejung et al. Nature genetics 2022 10 (Posted: Oct 28, 2022 9AM)

Genetic risk factors for autism include both rare and common variants. A study shows that rare copy number variants and common variants across 16p that contribute to autism risk functionally converge to downregulate the expression of a large group of neuronally expressed genes in the 16p subtelomeric region.

Rare coding variation provides insight into the genetic architecture and phenotypic context of autism
JM Fu et al, Nature Genetics, August 18, 2022 (Posted: Aug 18, 2022 1PM)

Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR)?=?0.001 (185 at FDR?=?0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk.

An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases
MJ Owen et al, Nat Comm, July 26, 2022 (Posted: Jul 26, 2022 7AM)

While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5?h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants

Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies
NC Rose et al, Genetics in Medicine, May 23, 2022 (Posted: May 24, 2022 8AM)

A total of 87 studies met inclusion criteria. Diagnostic odds ratios were significant (P < .0001) for T21, T18, and T13 for singleton and twin pregnancies. NIPS was accurate (=99.78%) in detecting sex chromosome aneuploidies. Performance for rare autosomal trisomies and copy number variants was variable. Use of NIPS reduced diagnostic tests by 31% to 79%. Conclusions regarding psychosocial outcomes could not be drawn owing to lack of data. Identification of maternal conditions was rare. NIPS is a highly accurate screening method for T21, T18, and T13 in both singleton and twin pregnancies.

Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants
K Hamanaka et al, Genome Medicine, April 26, 2022 (Posted: Apr 29, 2022 1PM)

Previous large-scale studies of de novo variants identified a number of genes associated with neurodevelopmental disorders (NDDs); however, it was also predicted that many NDD-associated genes await discovery. Such genes can be discovered by integrating copy number variants (CNVs), which have not been fully considered in previous studies, and increasing the sample size. We identified a total of 380 genes achieving statistical significance (5% false discovery rate), including 31 genes affected by de novo CNVs. Of the 380 genes, 52 have not previously been reported as NDD genes, and the data of de novo CNVs contributed to the significance of three genes (GLTSCR1, MARK2, and UBR3)

Clinical Characterization of Copy Number Variants Associated With Neurodevelopmental Disorders in a Large-scale Multiancestry Biobank.
Birnbaum Rebecca et al. JAMA psychiatry 2022 1 (3) 250-259 (Posted: Mar 03, 2022 8AM)

In this series of phenotypic association analyses including data from 24 877 individuals, the overall prevalence of NDD CNVs in the biobank was found to be 2.5%. NDD CNV carriers were enriched for congenital disorders and major depressive disorder, and the presence of NDD CNVs was found to be associated with several medical outcomes, including hypertension, obesity, and obesity-related phenotypes, specifically obstructive sleep apnea and increased body mass index.

Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA
JD Finkle et al, NPJ Precision Oncology, July 2021 (Posted: Jul 05, 2021 7AM)

Liquid biopsy is a valuable precision oncology tool that is increasingly used as a non-invasive approach to identify biomarkers, detect resistance mutations, monitor disease burden, and identify early recurrence. The Tempus xF liquid biopsy assay is a 105-gene, hybrid-capture, next-generation sequencing (NGS) assay that detects single-nucleotide variants, insertions/deletions, copy number variants, and chromosomal rearrangements.

Direct-to-consumer prenatal testing for multigenic or polygenic disorders: a position statement of the American College of Medical Genetics and Genomics (ACMG)
ACMG Board of Directors, Genetics in Medicine, June 28, 2021 (Posted: Jun 28, 2021 7AM)

While the issues surrounding direct-to-consumer testing for monogenic disease or disease caused by copy-number variants are complicated, they are even more complex for disorders that exhibit polygenic inheritance. As a result of increasing data points, the need for interpretation of and counseling about any type of genetic testing regarding these disorders has become exponentially more complex, and in most instances, is not a part of general clinical genetics practice. In this context, the emergence of direct-to-consumer testing for multi/polygenic diseases is particularly troubling.

Genome-wide cell-free DNA screening: a focus on copy-number variants
J Rafalko et al, Genetics in Medicine, June 21, 2021 (Posted: Jun 21, 2021 8AM)

Of 86,902 prenatal genome-wide cell-free DNA (cfDNA) screening tests, 4,121 were positive for a chromosome abnormality. This study examines 490 cases screen-positive for one or more subchromosomal copy-number variants (CNV) from genome-wide cfDNA screening. CNVs were identified in 0.56% of screened specimens. Of the 490 cases screen-positive for one or more CNV, diagnostic outcomes were available for 244 cases (50%). The overall PPV among the cases with diagnostic outcomes was 74.2% (95% CI: 68.1–79.5%) and 71.8% (95% CI: 65.5–77.4%) for “fetal-only” events.

Stepwise ABC system for classification of any type of genetic variant.
Houge Gunnar et al. European journal of human genetics : EJHG 2021 5 (Posted: May 14, 2021 8AM)

We present a variant classification model that can be an add-on or alternative to ACMG classification: A stepwise system that can classify any type of genetic variant (e.g., hypomorphic alleles, imprinted alleles, copy number variants, runs of homozygosity, enhancer variants, and variants related to traits). We call it the ABC system as the classification is first functional (A), then clinical (B), and a standard comment that fits the clinical question is selected (C).

Three years of clinical experience with a genome-wide cfDNA screening test for aneuploidies and copy-number variants
E Soster et al, Genetics in Medicine, March 17, 2021 (Posted: Mar 17, 2021 1PM)

Pregnant women have unprecedented choices for prenatal screening and testing. Cell-free DNA (cfDNA) offers the option to screen for aneuploidy of all chromosomes and genome-wide copy-number variants (CNVs), expanding screening beyond the common trisomies (“traditional” cfDNA). We sought to review the utilization trends and clinical performance characteristics of a commercially available genome-wide cfDNA test, with a subset having available diagnostic testing outcomes.

Genetic contributions to autism spectrum disorder.
Havdahl A et al. Psychological medicine 2021 1-14 (Posted: Mar 02, 2021 9AM)

This review summarizes recent developments in human genetics research in autism, complemented by epigenetic and transcriptomic findings. The clinical heterogeneity of autism is mirrored by a complex genetic architecture involving several types of common and rare variants, ranging from point mutations to large copy number variants.

Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia
CA Moreau et al, Nature Comms, October 19, 2020 (Posted: Oct 20, 2020 7AM)

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls.

Characterization of clinically relevant copy-number variants from exomes of patients with inherited heart disease and unexplained sudden cardiac death.
Singer Emma S et al. Genetics in medicine : official journal of the American College of Medical Genetics 2020 Sep (Posted: Sep 27, 2020 2PM)

Copy-number variant (CNV) analysis is increasingly performed in genetic diagnostics. We leveraged recent gene curation efforts and technical standards for interpretation and reporting of CNVs to characterize clinically relevant CNVs in patients with inherited heart disease and sudden cardiac death.

Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450
V Hlavac et al, J Per Med, August 2020 (Posted: Sep 03, 2020 7AM)

We briefly introduce the field of pharmacogenomics in two large pharmacogene superfamilies. Although the evidence needs further substantiation, somatic and copy number variants as well as rare variants and common polymorphisms in these genes could all affect response to cancer therapy. However, in all these areas, more comprehensive studies are needed.

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.

Association of Rare Copy Number Variants With Risk of Depression
KM Kendal et al. JAMA Psychiatry, April 17, 2019 (Posted: Apr 17, 2019 1PM)

Pathogenic copy number variants that affect gene expression contribute to genomic burden in cerebral palsy
MA Corbett et al,. NPJ Genomic Medicine, Decemeber 2018 (Posted: Dec 20, 2018 8AM)

Role of copy number variants in sudden cardiac death and related diseases: genetic analysis and translation into clinical practice.
Mates Jesus et al. European journal of human genetics : EJHG 2018 Mar (Posted: Mar 09, 2018 9AM)

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
CNV and Schizophrenia Working Group, Nature Genetics, November 21, 2016 (Posted: Nov 21, 2016 1PM)

Special report: chromosomal microarray for the genetic evaluation of patients with global developmental delay, intellectual disability, and autism spectrum disorder [PDF 455.39 KB]
Blue Cross Blue Shield Association, August 2015 (Posted: Sep 24, 2015 1PM)

The Science, Applications, and Ethical Concerns Surrounding Low Copy Number DNA Analysis.
Schulz Rebecca et al. Genet Test Mol Biomarkers 2015 Jun 19(6) 281-2 (Posted: Jun 10, 2015 3PM)

Copy Number Variations and Cognitive Phenotypes in Unselected Populations
K Mannik et al, JAMA May 26, 2015 (Posted: May 26, 2015 2PM)

A copy number variation map of the human genome.
Zarrei Mehdi et al. Nat. Rev. Genet. 2015 Mar (3) 172-83 (Posted: May 26, 2015 1PM)

Copy number variations in children with brain malformations and refractory epilepsy.
Wincent Josephine et al. Am. J. Med. Genet. A 2015 Mar (3) 512-23 (Posted: May 26, 2015 1PM)

Estimating copy numbers of alleles from population-scale high-throughput sequencing data.
Mimori Takahiro et al. BMC Bioinformatics 2015 S4 (Posted: May 26, 2015 1PM)

Rare structural genetic variation in human prion diseases.
Lukic Ana et al. Neurobiol. Aging 2015 May (5) 2004.e1-8 (Posted: May 26, 2015 1PM)

Copy number variations' effect on drug response still overlooked.
Willyard Cassandra et al. Nat. Med. 2015 Mar (3) 206 (Posted: May 26, 2015 1PM)

Copy number variation burden on asthma subgenome in normal cohorts identifies susceptibility markers.
Vishweswaraiah Sangeetha et al. Allergy Asthma Immunol Res 2015 May (3) 265-75 (Posted: May 26, 2015 1PM)

Copy-number variation and false positive prenatal aneuploidy screening results.
Snyder Matthew W et al. N. Engl. J. Med. 2015 Apr 23. (17) 1639-45 (Posted: May 26, 2015 1PM)

Structural variation mutagenesis of the human genome: Impact on disease and evolution.
Lupski James R et al. Environ. Mol. Mutagen. 2015 Apr 17. (Posted: May 26, 2015 1PM)

Genome wide analysis of novel copy number variations duplications/deletions of different epileptic patients in Saudi Arabia.
Naseer Muhammad Imran et al. BMC Genomics 2015 S10 (Posted: May 26, 2015 1PM)

The clinical utility of next-generation sequencing for identifying chromosome disease syndromes in human embryos.
Fan Junmei et al. Reprod. Biomed. Online 2015 Apr 9. (Posted: May 26, 2015 1PM)

Cerebral Palsy - Causes, pathways, and the role of genetic variants.
MacLennan Alastair H et al. Am. J. Obstet. Gynecol. 2015 May 20. (Posted: May 26, 2015 1PM)

Genomic microarray in fetuses with increased nuchal translucency and normal karyotype - a systematic review and meta-analysis.
Grande Maribel et al. Ultrasound Obstet Gynecol 2015 Apr 20. (Posted: May 26, 2015 1PM)

Contribution of copy number variants (CNVs) to congenital, unexplained intellectual and developmental disabilities in Lebanese patients.
Choucair Nancy et al. Mol Cytogenet 2015 26 (Posted: May 26, 2015 1PM)

The variation game: Cracking complex genetic disorders with NGS and omics data.
Cui Hongzhu et al. Methods 2015 Jun 1. 18-31 (Posted: May 26, 2015 1PM)

Clinical implications of copy number variations in autoimmune disorders.
Yim Seon-Hee et al. Korean J. Intern. Med. 2015 May (3) 294-304 (Posted: May 26, 2015 1PM)

Cognitive Phenotypes and Genomic Copy Number Variations
JR Lupski, JAMA< May 26, 2015 (Posted: May 26, 2015 1PM)

Interactions between Obesity-Related Copy Number Variants and Dietary Behaviors in Childhood Obesity.
Zhang Dandan et al. Nutrients 2015 (4) 3054-66 (Posted: May 08, 2015 10AM)

Copy number variants in attention-deficit hyperactive disorder: identification of the 15q13 deletion and its functional role.
Valbonesi Stefano et al. Psychiatr. Genet. 2015 Apr (2) 59-70 (Posted: Apr 02, 2015 1PM)

Increased frequency of de novo copy number variants in congenital heart disease by integrative analysis of single nucleotide polymorphism array and exome sequence data.
Glessner Joseph T et al. Circ. Res. 2014 Oct 24. (10) 884-96 (Posted: Feb 27, 2015 11AM)

Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system.
Docampo Elisa et al. Pain 2014 Jun (6) 1102-9 (Posted: Feb 12, 2015 8AM)


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.
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