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Article ; Online: A call for increased inclusivity and global representation in pharmacogenetic testing.

Kennedy, April / Ma, Gabriel / Manshaei, Roozbeh / Jobling, Rebekah K / Kim, Raymond H / Lewis, Tamorah / Cohn, Iris

2024 Volume 9, Issue 1, Page(s) 13

Abstract: Commercial pharmacogenetic testing panels capture a fraction of the genetic variation underlying medication metabolism and predisposition to adverse reactions. In this study we compared variation in six pharmacogenes detected by whole genome sequencing ( ... ...

Abstract	Commercial pharmacogenetic testing panels capture a fraction of the genetic variation underlying medication metabolism and predisposition to adverse reactions. In this study we compared variation in six pharmacogenes detected by whole genome sequencing (WGS) to a targeted commercial panel in a cohort of 308 individuals with family history of pediatric heart disease. In 1% of the cohort, WGS identified rare variants that altered the interpretation of metabolizer status and would thus prevent potential errors in gene-based dosing.
Language	English
Publishing date	2024-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2813848-X
ISSN	2056-7944 ; 2056-7944
ISSN (online)	2056-7944
ISSN	2056-7944
DOI	10.1038/s41525-024-00403-1
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Article ; Online: GeneTerpret: a customizable multilayer approach to genomic variant prioritization and interpretation.

Manshaei, Roozbeh / DeLong, Sean / Andric, Veronica / Joshi, Esha / Okello, John B A / Dhir, Priya / Somerville, Cherith / Farncombe, Kirsten M / Kalbfleisch, Kelsey / Jobling, Rebekah K / Scherer, Stephen W / Kim, Raymond H / Hosseini, S Mohsen

BMC medical genomics

2022 Volume 15, Issue 1, Page(s) 31

Abstract: Background: Variant interpretation is the main bottleneck in medical genomic sequencing efforts. This usually involves genome analysts manually searching through a multitude of independent databases, often with the aid of several, mostly independent, ... ...

Abstract	Background: Variant interpretation is the main bottleneck in medical genomic sequencing efforts. This usually involves genome analysts manually searching through a multitude of independent databases, often with the aid of several, mostly independent, computational tools. To streamline variant interpretation, we developed the GeneTerpret platform which collates data from current interpretation tools and databases, and applies a phenotype-driven query to categorize the variants identified in the genome(s). The platform assigns quantitative validity scores to genes by query and assembly of the genotype-phenotype data, sequence homology, molecular interactions, expression data, and animal models. It also uses the American College of Medical Genetics and Genomics (ACMG) criteria to categorize variants into five tiers of pathogenicity. The final output is a prioritized list of potentially causal variants/genes. Results: We tested GeneTerpret by comparing its performance to expert-curated genes (ClinGen's gene-validity database) and variant pathogenicity reports (DECIPHER database). Output from GeneTerpret was 97.2% and 83.5% concordant with the expert-curated sources, respectively. Additionally, similar concordance was observed when GeneTerpret's performance was compared with our internal expert-interpreted clinical datasets. Conclusions: GeneTerpret is a flexible platform designed to streamline the genome interpretation process, through a unique interface, with improved ease, speed and accuracy. This modular and customizable system allows the user to tailor the component-programs in the analysis process to their preference. GeneTerpret is available online at https://geneterpret.com .
MeSH term(s)	Genetic Variation ; Genome, Human ; Genomics ; Humans ; Phenotype ; Software ; United States
Language	English
Publishing date	2022-02-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2411865-5
ISSN	1755-8794 ; 1755-8794
ISSN (online)	1755-8794
ISSN	1755-8794
DOI	10.1186/s12920-022-01166-3
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Article ; Online: SCIP: software for efficient clinical interpretation of copy number variants detected by whole-genome sequencing

Ding, Qiliang / Somerville, Cherith / Manshaei, Roozbeh / Trost, Brett / Reuter, Miriam S. / Kalbfleisch, Kelsey / Stanley, Kaitlin / Okello, John B. A. / Hosseini, S. Mohsen / Liston, Eriskay / Curtis, Meredith / Zarrei, Mehdi / Higginbotham, Edward J. / Chan, Ada J. S. / Engchuan, Worrawat / Thiruvahindrapuram, Bhooma / Scherer, Stephen W. / Kim, Raymond H. / Jobling, Rebekah K.

Hum Genet. 2023 Feb., v. 142, no. 2, p. 201-216

2023 , Page(s) 201–216

Abstract: Copy number variants (CNVs) represent major etiologic factors in rare genetic diseases. Current clinical CNV interpretation workflows require extensive back-and-forth with multiple tools and databases. This increases complexity and time burden, ... ...

Abstract	Copy number variants (CNVs) represent major etiologic factors in rare genetic diseases. Current clinical CNV interpretation workflows require extensive back-and-forth with multiple tools and databases. This increases complexity and time burden, potentially resulting in missed genetic diagnoses. We present the Suite for CNV Interpretation and Prioritization (SCIP), a software package for the clinical interpretation of CNVs detected by whole-genome sequencing (WGS). The SCIP Visualization Module near-instantaneously displays all information necessary for CNV interpretation (variant quality, population frequency, inheritance pattern, and clinical relevance) on a single page—supported by modules providing variant filtration and prioritization. SCIP was comprehensively evaluated using WGS data from 1027 families with congenital cardiac disease and/or autism spectrum disorder, containing 187 pathogenic or likely pathogenic (P/LP) CNVs identified in previous curations. SCIP was efficient in filtration and prioritization: a median of just two CNVs per case were selected for review, yet it captured all P/LP findings (92.5% of which ranked 1st). SCIP was also able to identify one pathogenic CNV previously missed. SCIP was benchmarked against AnnotSV and a spreadsheet-based manual workflow and performed superiorly than both. In conclusion, SCIP is a novel software package for efficient clinical CNV interpretation, substantially faster and more accurate than previous tools (available at https://github.com/qd29/SCIP , a video tutorial series is available at https://bit.ly/SCIPVideos).
Keywords	autism ; computer software ; etiology ; filtration ; heart diseases ; prioritization
Language	English
Dates of publication	2023-02
Size	p. 201-216
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	223009-4
ISSN	1432-1203 ; 0340-6717
ISSN (online)	1432-1203
ISSN	0340-6717
DOI	10.1007/s00439-022-02494-1
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Article ; Online: Trio genome sequencing for developmental delay and pediatric heart conditions: A comparative microcost analysis.

Jegathisawaran, Jathishinie / Tsiplova, Kate / Hayeems, Robin Z / Marshall, Christian R / Stavropoulos, Dimitri J / Pereira, Sergio L / Thiruvahindrapuram, Bhooma / Liston, Eriskay / Reuter, Miriam S / Manshaei, Roozbeh / Cohn, Iris / Jobling, Rebekah / Kim, Raymond H / Mital, Seema / Ungar, Wendy J

Genetics in medicine : official journal of the American College of Medical Genetics

2022 Volume 24, Issue 5, Page(s) 1027–1036

Abstract: Purpose: Genome sequencing (GS) can aid clinical management of multiple pediatric conditions. Insurers require accurate cost information to inform funding and implementation decisions. The objective was to compare the laboratory workflows and microcosts ...

Abstract	Purpose: Genome sequencing (GS) can aid clinical management of multiple pediatric conditions. Insurers require accurate cost information to inform funding and implementation decisions. The objective was to compare the laboratory workflows and microcosts of trio GS testing in children with developmental delay (DD) and in children with cardiac conditions. Methods: Cost items related to each step in trio GS (child and 2 parents) for both populations were identified and measured. Program costs over 5 years were estimated. Probabilistic and deterministic analyses were conducted. Results: The mean cost per trio GS was CAD$6634.11 (95% CI = 6352.29-6913.40) for DD and CAD$8053.10 (95% CI = 7699.30-8558.10) for cardiac conditions. The 5-year program cost was CAD$28.11 million (95% CI = 26.91-29.29) for DD and CAD$5.63 million (95% CI = 5.38-5.98) for cardiac conditions. Supplies constituted the largest cost component for both populations. The higher cost per sample for the population with cardiac conditions was due to the inclusion of pharmacogenomics, higher bioinformatics labor costs, and a more labor intensive case review. Conclusion: This analysis indicated important variation in trio GS workflow and costs between pediatric populations in a single institution. Enhanced understanding of the clinical utility and costs of GS can inform harmonization and implementation decision-making.
MeSH term(s)	Base Sequence ; Child ; Chromosome Mapping ; Humans ; Parents ; Pharmacogenetics
Language	English
Publishing date	2022-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1455352-1
ISSN	1530-0366 ; 1098-3600
ISSN (online)	1530-0366
ISSN	1098-3600
DOI	10.1016/j.gim.2022.01.020
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Article ; Online: Genome sequencing broadens the range of contributing variants with clinical implications in schizophrenia.

Mojarad, Bahareh A / Yin, Yue / Manshaei, Roozbeh / Backstrom, Ian / Costain, Gregory / Heung, Tracy / Merico, Daniele / Marshall, Christian R / Bassett, Anne S / Yuen, Ryan K C

Translational psychiatry

2021 Volume 11, Issue 1, Page(s) 84

Abstract: The range of genetic variation with potential clinical implications in schizophrenia, beyond rare copy number variants (CNVs), remains uncertain. We therefore analyzed genome sequencing data for 259 unrelated adults with schizophrenia from a well- ... ...

Abstract	The range of genetic variation with potential clinical implications in schizophrenia, beyond rare copy number variants (CNVs), remains uncertain. We therefore analyzed genome sequencing data for 259 unrelated adults with schizophrenia from a well-characterized community-based cohort previously examined with chromosomal microarray for CNVs (none with 22q11.2 deletions). We analyzed these genomes for rare high-impact variants considered causal for neurodevelopmental disorders, including single-nucleotide variants (SNVs) and small insertions/deletions (indels), for potential clinical relevance based on findings for neurodevelopmental disorders. Also, we investigated a novel variant type, tandem repeat expansions (TREs), in 45 loci known to be associated with monogenic neurological diseases. We found several of these variants in this schizophrenia population suggesting that these variants have a wider clinical spectrum than previously thought. In addition to known pathogenic CNVs, we identified 11 (4.3%) individuals with clinically relevant SNVs/indels in genes converging on schizophrenia-relevant pathways. Clinical yield was significantly enriched in females and in those with broadly defined learning/intellectual disabilities. Genome analyses also identified variants with potential clinical implications, including TREs (one in DMPK; two in ATXN8OS) and ultra-rare loss-of-function SNVs in ZMYM2 (a novel candidate gene for schizophrenia). Of the 233 individuals with no pathogenic CNVs, we identified rare high-impact variants (i.e., clinically relevant or with potential clinical implications) for 14 individuals (6.0%); some had multiple rare high-impact variants. Mean schizophrenia polygenic risk score was similar between individuals with and without clinically relevant rare genetic variation; common variants were not sufficient for clinical application. These findings broaden the individual and global picture of clinically relevant genetic risk in schizophrenia, and suggest the potential translational value of genome sequencing as a single genetic technology for schizophrenia.
MeSH term(s)	Adult ; Cohort Studies ; DNA Copy Number Variations ; Female ; Genetic Predisposition to Disease ; Humans ; Intellectual Disability ; Neurodevelopmental Disorders/genetics ; Schizophrenia/genetics
Language	English
Publishing date	2021-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-021-01211-2
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Article ; Online: Assessment of the Implementation of Pharmacogenomic Testing in a Pediatric Tertiary Care Setting.

Cohn, Iris / Manshaei, Roozbeh / Liston, Eriskay / Okello, John B A / Khan, Reem / Curtis, Meredith R / Krupski, Abby J / Jobling, Rebekah K / Kalbfleisch, Kelsey / Paton, Tara A / Reuter, Miriam S / Hayeems, Robin Z / Verstegen, Ruud H J / Goldman, Aaron / Kim, Raymond H / Ito, Shinya

JAMA network open

2021 Volume 4, Issue 5, Page(s) e2110446

Abstract: Importance: Pharmacogenomic (PGx) testing provides preemptive pharmacotherapeutic guidance regarding the lack of therapeutic benefit or adverse drug reactions of PGx targeted drugs. Pharmacogenomic information is of particular value among children with ... ...

Abstract	Importance: Pharmacogenomic (PGx) testing provides preemptive pharmacotherapeutic guidance regarding the lack of therapeutic benefit or adverse drug reactions of PGx targeted drugs. Pharmacogenomic information is of particular value among children with complex medical conditions who receive multiple medications and are at higher risk of developing adverse drug reactions. Objectives: To assess the implementation outcomes of a PGx testing program comprising both a point-of-care model that examined targeted drugs and a preemptive model informed by whole-genome sequencing that evaluated a broad range of drugs for potential therapy among children in a pediatric tertiary care setting. Design, setting, and participants: This cohort study was conducted at The Hospital for Sick Children in Toronto, Ontario, from January 2017 to September 2020. Pharmacogenomic analyses were performed among 172 children who were categorized into 2 groups: a point-of-care cohort and a preemptive cohort. The point-of-care cohort comprised 57 patients referred to the consultation clinic for planned therapy with PGx targeted drugs and/or for adverse drug reactions, including lack of therapeutic benefit, after the receipt of current or past medications. The preemptive cohort comprised 115 patients who received exploratory whole-genome sequencing-guided PGx testing for their heart conditions from the cardiac genome clinic at the Ted Rogers Centre for Heart Research. Exposures: Patients received PGx analysis of whole-genome sequencing data and/or multiplex genotyping of 6 pharmacogenes (CYP2C19, CYP2C9, CYP2D6, CYP3A5, VKORC1, and TPMT) that have established PGx clinical guidelines. Main outcomes and measures: The number of patients for whom PGx test results warranted deviation from standard dosing regimens. Results: A total of 172 children (mean [SD] age, 8.5 [5.6] years; 108 boys [62.8%]) were enrolled in the study. In the point-of-care cohort, a median of 2 target genes (range, 1-5 genes) were investigated per individual, with CYP2C19 being the most frequently examined; genotypes in 21 of 57 children (36.8%) were incompatible with standard treatment regimens. As expected from population allelic frequencies, among the 115 children in the whole-genome sequencing-guided preemptive cohort, 92 children (80.0%) were recommended to receive nonstandard treatment regimens for potential drug therapies based on their 6-gene pharmacogenetic profile. Conclusions and relevance: In this cohort study, among both the point-of-care and preemptive cohorts, the multiplex PGx testing program provided dosing recommendations that deviated from standard regimens at an overall rate that was similar to the population frequencies of relevant variants.
MeSH term(s)	Adolescent ; Child ; Cohort Studies ; Female ; Genetic Testing/statistics & numerical data ; Humans ; Male ; Ontario ; Pediatrics/statistics & numerical data ; Pharmacogenomic Testing/statistics & numerical data ; Pilot Projects ; Point-of-Care Testing/statistics & numerical data ; Precision Medicine/methods ; Precision Medicine/statistics & numerical data ; Tertiary Healthcare/statistics & numerical data
Language	English
Publishing date	2021-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2021.10446
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Article ; Online: SCIP: software for efficient clinical interpretation of copy number variants detected by whole-genome sequencing.

Ding, Qiliang / Somerville, Cherith / Manshaei, Roozbeh / Trost, Brett / Reuter, Miriam S / Kalbfleisch, Kelsey / Stanley, Kaitlin / Okello, John B A / Hosseini, S Mohsen / Liston, Eriskay / Curtis, Meredith / Zarrei, Mehdi / Higginbotham, Edward J / Chan, Ada J S / Engchuan, Worrawat / Thiruvahindrapuram, Bhooma / Scherer, Stephen W / Kim, Raymond H / Jobling, Rebekah K

Human genetics

2022 Volume 142, Issue 2, Page(s) 201–216

Abstract	Copy number variants (CNVs) represent major etiologic factors in rare genetic diseases. Current clinical CNV interpretation workflows require extensive back-and-forth with multiple tools and databases. This increases complexity and time burden, potentially resulting in missed genetic diagnoses. We present the Suite for CNV Interpretation and Prioritization (SCIP), a software package for the clinical interpretation of CNVs detected by whole-genome sequencing (WGS). The SCIP Visualization Module near-instantaneously displays all information necessary for CNV interpretation (variant quality, population frequency, inheritance pattern, and clinical relevance) on a single page-supported by modules providing variant filtration and prioritization. SCIP was comprehensively evaluated using WGS data from 1027 families with congenital cardiac disease and/or autism spectrum disorder, containing 187 pathogenic or likely pathogenic (P/LP) CNVs identified in previous curations. SCIP was efficient in filtration and prioritization: a median of just two CNVs per case were selected for review, yet it captured all P/LP findings (92.5% of which ranked 1st). SCIP was also able to identify one pathogenic CNV previously missed. SCIP was benchmarked against AnnotSV and a spreadsheet-based manual workflow and performed superiorly than both. In conclusion, SCIP is a novel software package for efficient clinical CNV interpretation, substantially faster and more accurate than previous tools (available at https://github.com/qd29/SCIP , a video tutorial series is available at https://bit.ly/SCIPVideos ).
MeSH term(s)	Humans ; DNA Copy Number Variations ; Autism Spectrum Disorder ; Whole Genome Sequencing ; Software ; Rare Diseases
Language	English
Publishing date	2022-11-14
Publishing country	Germany
Document type	Journal Article
ZDB-ID	223009-4
ISSN	1432-1203 ; 0340-6717
ISSN (online)	1432-1203
ISSN	0340-6717
DOI	10.1007/s00439-022-02494-1
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Article ; Online: Gene copy number variation and pediatric mental health/neurodevelopment in a general population.

Zarrei, Mehdi / Burton, Christie L / Engchuan, Worrawat / Higginbotham, Edward J / Wei, John / Shaikh, Sabah / Roslin, Nicole M / MacDonald, Jeffrey R / Pellecchia, Giovanna / Nalpathamkalam, Thomas / Lamoureux, Sylvia / Manshaei, Roozbeh / Howe, Jennifer / Trost, Brett / Thiruvahindrapuram, Bhooma / Marshall, Christian R / Yuen, Ryan K C / Wintle, Richard F / Strug, Lisa J /

Stavropoulos, Dimitri J / Vorstman, Jacob A S / Arnold, Paul / Merico, Daniele / Woodbury-Smith, Marc / Crosbie, Jennifer / Schachar, Russell J / Scherer, Stephen W

Human molecular genetics

2023 Volume 32, Issue 15, Page(s) 2411–2421

Abstract: We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health and cognition in a community sample of 7100 unrelated children and youth of European or East Asian ancestry (Spit ... ...

Abstract	We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health and cognition in a community sample of 7100 unrelated children and youth of European or East Asian ancestry (Spit for Science). Clinically significant or susceptibility CNVs were present in 3.9% of participants and were associated with elevated scores on a continuous measure of attention-deficit/hyperactivity disorder (ADHD) traits (P = 5.0 × 10-3), longer response inhibition (a cognitive deficit found in several mental health and neurodevelopmental disorders; P = 1.0 × 10-2) and increased prevalence of mental health diagnoses (P = 1.9 × 10-6, odds ratio: 3.09), specifically ADHD, autism spectrum disorder anxiety and learning problems/learning disorder (P's < 0.01). There was an increased burden of rare deletions in gene-sets related to brain function or expression in brain associated with more ADHD traits. With the current mental health crisis, our data established a baseline for delineating genetic contributors in pediatric-onset conditions.
MeSH term(s)	Adolescent ; Humans ; Child ; Mental Health ; DNA Copy Number Variations/genetics ; Autism Spectrum Disorder/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Attention Deficit Disorder with Hyperactivity/epidemiology ; Attention Deficit Disorder with Hyperactivity/genetics ; Gene Dosage
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddad074
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Article ; Online: Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.

Fehlings, Darcy L / Zarrei, Mehdi / Engchuan, Worrawat / Sondheimer, Neal / Thiruvahindrapuram, Bhooma / MacDonald, Jeffrey R / Higginbotham, Edward J / Thapa, Ritesh / Behlim, Tarannum / Aimola, Sabrina / Switzer, Lauren / Ng, Pamela / Wei, John / Danthi, Prakroothi S / Pellecchia, Giovanna / Lamoureux, Sylvia / Ho, Karen / Pereira, Sergio L / de Rijke, Jill /

Sung, Wilson W L / Mowjoodi, Alireza / Howe, Jennifer L / Nalpathamkalam, Thomas / Manshaei, Roozbeh / Ghaffari, Siavash / Whitney, Joseph / Patel, Rohan V / Hamdan, Omar / Shaath, Rulan / Trost, Brett / Knights, Shannon / Samdup, Dawa / McCormick, Anna / Hunt, Carolyn / Kirton, Adam / Kawamura, Anne / Mesterman, Ronit / Gorter, Jan Willem / Dlamini, Nomazulu / Merico, Daniele / Hilali, Murto / Hirschfeld, Kyle / Grover, Kritika / Bautista, Nelson X / Han, Kara / Marshall, Christian R / Yuen, Ryan K C / Subbarao, Padmaja / Azad, Meghan B / Turvey, Stuart E / Mandhane, Piush / Moraes, Theo J / Simons, Elinor / Maxwell, George / Shevell, Michael / Costain, Gregory / Michaud, Jacques L / Hamdan, Fadi F / Gauthier, Julie / Uguen, Kevin / Stavropoulos, Dimitri J / Wintle, Richard F / Oskoui, Maryam / Scherer, Stephen W

Nature genetics

2024 Volume 56, Issue 4, Page(s) 585–594

Abstract: We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of ... ...

Abstract	We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.
MeSH term(s)	Humans ; Child ; DNA Copy Number Variations/genetics ; Cerebral Palsy/genetics ; Mutation ; Whole Genome Sequencing ; Genomics
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-024-01686-x
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Article: Genes and Pathways Implicated in Tetralogy of Fallot Revealed by Ultra-Rare Variant Burden Analysis in 231 Genome Sequences.

Frontiers in genetics

2020 Volume 11, Page(s) 957

Abstract: Recent genome-wide studies of rare genetic variants have begun to implicate novel mechanisms for tetralogy of Fallot (TOF), a severe congenital heart defect (CHD). To provide statistical support for case-only data without parental genomes, we re-analyzed ...

Abstract	Recent genome-wide studies of rare genetic variants have begun to implicate novel mechanisms for tetralogy of Fallot (TOF), a severe congenital heart defect (CHD). To provide statistical support for case-only data without parental genomes, we re-analyzed genome sequences of 231 individuals with TOF (
Language	English
Publishing date	2020-09-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2020.00957
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